Publications by authors named "Xiaoyan Liang"

156 Publications

Numerical analysis of the DKDP-based high-energy optical parametric chirped pulse amplifier for a 100  PW class laser.

Appl Opt 2021 May;60(13):3842-3848

An optical parametric chirped pulse amplifier (OPCPA) based on a large-aperture DKDP crystal and pumped by a 10 kJ level Nd:glass laser can serve as the final amplifier for a 100 PW level laser. A comprehensive numerical investigation on such a high-energy OPCPA is presented in this work. The effects on the efficiency-bandwidth product induced by the deuteration level, absorption loss, temperature variation, and optimization of zero-phase-mismatch wavelength (ZPMW) are analyzed in detail. Based on the analysis above, a three-dimensional numerical simulation taking into account the effects of pumping depletion, diffraction, and walk-off shows that, by optimization of ZPMW, broadband (over 210 nm spectral width in FWHM) and high efficiency (${\gt}37\%$) amplification can be realized in the DKDP crystal even with a moderate deuteration level of 70%, which can relax the requirement of a high deuteration level in a large-aperture DKDP crystal. The numerical analysis can provide meaningful guidance for the design and construction of 100 PW class laser systems.
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http://dx.doi.org/10.1364/AO.423191DOI Listing
May 2021

Chitosan coated pH-responsive metal-polyphenol delivery platform for melanoma chemotherapy.

Carbohydr Polym 2021 Jul 27;264:118000. Epub 2021 Mar 27.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, PR China. Electronic address:

The safe and effective drug delivery system is important for cancer therapy. Here in, we first constructed a delivery system Cabazitaxel(Cab)@MPN/CS between metal-polyphenol (MPN) and chitosan (CS) to deliver Cab for melanoma therapy. The preparation process is simple, green, and controllable. After introducing CS coating, the drug loading was improved from 7.56 % to 9.28 %. Cab@MPN/CS NPs released Cab continuously under acid tumor microenvironment. The zeta potential of Cab@MPN/CS NPs could be controlled by changing the ratio of Cab@MPN and CS solutions. The positively charged Cab@MPN/CS accelerate B16F10 cell internalization. After internalized, Cab@MPN/CS NPs could escape from lysosomes via the proton sponge effect. The permeability of CS promotes the penetration of Cab@MPN/CS to the deeper B16F10 tumor spheroids. In vivo results showed that Cab@MPN/CS NPs have a longer retention time in tumor tissues and significantly inhibit tumor growth by up-regulating TUNEL expression and down-regulating KI67 and CD31 expression. Thus, this delivery system provides a promising strategy for the tumor therapy in clinic.
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http://dx.doi.org/10.1016/j.carbpol.2021.118000DOI Listing
July 2021

Short-Term High-Intensity Treadmill Exercise Promotes Ceramide-Dependent Extracellular Vesicle Secretion in the Central Nervous System of Mice.

Med Sci Monit 2021 Apr 21;27:e929609. Epub 2021 Apr 21.

Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China (mainland).

BACKGROUND A lack of physical exercise, a critical aspect of a healthy lifestyle, contributes to several cerebral diseases, such as cognitive impairment, Parkinson disease (PD), and Alzheimer disease (AD). The purpose of the present study was to evaluate the effect of physical exercise on cerebral disease via released extracellular vesicles (EVs). MATERIAL AND METHODS Short-term high-intensity treadmill exercise was applied to assess the effect of physical activity on EVs in the serum and brain tissue. Immunofluorescence staining and western blot analysis were used to analyze biomarkers of EVs, including TSG101, HSC70, and CD63. Nanoparticle tracking analysis (NTA) was used to analyze the size and concentration of EVs. RESULTS Short-term high-intensity exercise increased the number of neuronal EVs in the brain. In the peripheral blood serum, the level of HSC70 showed a temporary increase after exercise and quickly returned to the normal level, whereas the levels of CD63 and TSG101 showed no obvious change in response to physical exercise. In brain tissue, the levels of HSC70 and TSG101 increased dramatically after exercise, while the level of CD63 remained unchanged. The concentration of EVs was significantly increased after exercise, while the mean diameter of the EVs showed no significant change. The levels of ceramide were significantly increased after exercise, and quickly returned to normal levels. CONCLUSIONS These data suggest that the secretion of EVs in the brain and blood is a transitory response to physical exercise and is dependent on ceramide synthesis.
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http://dx.doi.org/10.12659/MSM.929609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074573PMC
April 2021

Triptolide Induces Leydig Cell Apoptosis by Disrupting Mitochondrial Dynamics in Rats.

Front Pharmacol 2021 9;12:616803. Epub 2021 Mar 9.

Reproductive Medicine Research Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Triptolide is widely used in the clinical treatment of various diseases. Side effects, including reproductive toxicity to male patients, limit its application. However, no detailed mechanisms or potential intervention targets have been reported. In this study, we show that triptolide activated the mitochondrial apoptosis pathway in rat testicular Leydig cells and induced apoptosis both and , which may cause hypoleydigism and impair spermatogenesis. Mechanistically, triptolide-induced dynamin-related protein 1 (Drp1) overexpression, which interfered with mitochondrial dynamic stability to activate the mitochondrial apoptosis pathway. Mdivi-1, a selective Drp1 inhibitor, partially reversed the mitochondrial dynamic disturbance and rat testicular Leydig cell apoptosis induced by triptolide. Inhibiting Drp1 over-activation may be a new strategy for mitigating the reproductive toxicity of triptolide.
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http://dx.doi.org/10.3389/fphar.2021.616803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985071PMC
March 2021

Study on the regulatory mechanism of the earthworm microbial community in vitro and in vivo under cadmium stress.

Environ Pollut 2021 Jun 13;279:116891. Epub 2021 Mar 13.

College of Resources and Environmental Science, Northeast Agricultural University, Harbin, China. Electronic address:

In this paper, cadmium (Cd) stress tests were performed on Eisenia fetida in sterile artificial soil, and its regulatory mechanism between microbial communities in vivo and in vitro after Cd stress was explored. In the test, 0, 50, 100, 125, 250 and 500 mg kg Cd stress concentrations were implemented. After long-term and short-term stress, the microbes in the earthworms and the soil were cultured with ECO plates. The data statistics of carbon source utilization intensity were carried out using the method developed by our team. CCA was scientifically integrated into TOPSIS to establish a new data analysis model to find the regulatory nodes after stress (Ning et al., 2020). Macro gene sequencing technology revealed that the species with the highest absolute abundance in the microbial communities in vivo and in vitro were all unnamed new species. It was confirmed that the HBA gene, NEUROD1 gene and ABCA3 gene were the regulatory genes of the microbial community in the earthworms under Cd stress, while the TC.FEV.OM gene and cheBR gene were the main regulatory genes of the microbial community in the soil. These results provide a scientific and theoretical reference and model basis for the bioremediation of Cd-contaminated soil and the detoxification mechanism of earthworms.
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http://dx.doi.org/10.1016/j.envpol.2021.116891DOI Listing
June 2021

Novel endoscopic management for small gastric submucosal tumors: A single-center experience (with video).

Dig Liver Dis 2021 Mar 16. Epub 2021 Mar 16.

Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Electronic address:

Background And Aims: To explore the novel treatment of small gastric submucosal tumors (SMTs) originating from the muscularis propria layer (SMT-MPs), we utilized endoscopic band ligation (EBL) with a precut of the covering mucosa.

Methods: From Jan. 2012 to Dec. 2019, 111 patients with 124 gastric SMT-MPs were treated by precutting EBL. The clinical characteristics, operation duration, postoperative adverse events, and follow-up profiles were retrospectively collected.

Results: A total of 124 tumors from 111 patients were successfully treated by precutting EBL. No adverse events, including perforation and major bleeding, were observed. Furthermore, 93 patients (83.8%) underwent endoscopic surveillance postoperatively, and during the follow-up period, no local recurrence was detected.

Conclusions: Precutting EBL appears to be a safe and simple method for removing gastric SMT-MPs < 16 mm (mainly indicated for potentially malignant GISTs), but further studies with longer follow-up are needed to assess the radicality of this intervention.
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http://dx.doi.org/10.1016/j.dld.2021.02.014DOI Listing
March 2021

Metabolomics-driven gene mining and genetic improvement of tolerance to salt-induced osmotic stress in maize.

New Phytol 2021 Mar 5. Epub 2021 Mar 5.

State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing, 100094, China.

The farmland of the world's main corn-producing area is increasingly affected by salt stress. Therefore, the breeding of salt-tolerant cultivars is necessary for the long-term sustainability of global corn production. Previous studies have shown that natural maize varieties display a large diversity of salt tolerance, yet the genetic variants underlying such diversity remain poorly discovered and applied, especially those mediating the tolerance to salt-induced osmotic stress (SIOS). Here we report a metabolomics-driven understanding and genetic improvement of maize SIOS tolerance. Using a LC-MS-based untargeted metabolomics approach, we profiled the metabolomes of 266 maize inbred lines under control and salt conditions, and then identified 37 metabolite biomarkers of SIOS tolerance (METO1-37). Follow-up metabolic GWAS (mGWAS) and genotype-to-phenotype modeling identified 10 candidate genes significantly associating with the SIOS tolerance and METO abundances. Furthermore, we validated that a citrate synthase, a glucosyltransferase and a cytochrome P450 underlie the genotype-METO-SIOS tolerance associations, and showed that their favorable alleles additively improve the SIOS tolerance of elite maize inbred lines. Our study provides a novel insight into the natural variation of maize SIOS tolerance, which boosts the genetic improvement of maize salt tolerance, and demonstrates a metabolomics-based approach for mining crop genes associated with this complex agronomic trait.
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http://dx.doi.org/10.1111/nph.17323DOI Listing
March 2021

Maipomycin A, a Novel Natural Compound With Promising Anti-biofilm Activity Against Gram-Negative Pathogenic Bacteria.

Front Microbiol 2020 12;11:598024. Epub 2021 Jan 12.

Shenzhen Key Laboratory of Marine Bioresource and Eco-Environmental Science, Shenzhen Engineering Laboratory for Marine Algal Biotechnology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.

Pathogenic bacterial biofilms play an important role in recurrent nosocomial and medical device-related infections. Once occurred, the complex structure of the biofilm promotes the development of antibiotic resistance and becomes extremely difficult to eradicate. Here we describe a novel and effective anti-biofilm compound maipomycin A (MaiA), which was isolated from the metabolites of a rare actinomycete strain XY-R10. Its structure was deduced from analyses of spectral data and confirmed by single-crystal X-ray crystallography. This natural product demonstrated a broad spectrum of anti-biofilm activities against Gram-negative bacteria. Interestingly, the addition of Fe(II) or Fe(III) ions could block the biofilm inhibition activity of MaiA because it is an iron chelator. However, not all iron chelators showed biofilm inhibition activity, suggesting that MaiA prevents biofilm formation through a specific yet currently undefined pathway. Furthermore, MaiA acts as a synergist to enhance colistin efficacy against . Our results indicate that MaiA may potentially serve as an effective antibiofilm agent to prevent Gram-negative biofilm formation in future clinical applications.
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http://dx.doi.org/10.3389/fmicb.2020.598024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835661PMC
January 2021

Development and validation of a model for individualized prediction of cervical insufficiency risks in patients undergoing IVF/ICSI treatment.

Reprod Biol Endocrinol 2021 Jan 7;19(1). Epub 2021 Jan 7.

Reproductive Medicine Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.

Background: Women who conceived with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) are more likely to experience adverse pregnancy outcomes than women who conceived naturally. Cervical insufficiency (CI) is one of the important causes of miscarriage and premature birth, however there is no published data available focusing on the potential risk factors predicting CI occurrence in women who received IVF/ICSI treatment. This study aimed to identify the risk factors that could be integrated into a predictive model for CI, which could provide further personalized and clinically specific information related to the incidence of CI after IVF/ICSI treatment.

Patients And Methods: This retrospective study included 4710 patients who conceived after IVF/ICSI treatment from Jan 2011 to Dec 2018 at a public university hospital. The patients were randomly divided into development (n = 3108) and validation (n = 1602) samples for the building and testing of the nomogram, respectively. Multivariate logistic regression was developed on the basis of pre-pregnancy clinical covariates assessed for their association with CI occurrence.

Results: A total of 109 patients (2.31%) experienced CI among all the enrolled patients. Body mass index (BMI), basal serum testosterone (T), gravidity and uterine length were associated with CI occurrence. The statistical nomogram was built based on BMI, serum T, gravidity and uterine length, with an area under the curve (AUC) of 0.84 (95% confidence interval: 0.76-0.90) for the developing cohort. The AUC for the validation cohort was 0.71 (95% confidence interval: 0.69-0.83), showing a satisfactory goodness-of-fit and discrimination ability in this nomogram.

Conclusion: The user-friendly nomogram which graphically represents the risk factors and a pre-pregnancy predicted tool for the incidence of CI in patients undergoing IVF/ICSI treatment, provides a useful guide for medical staff on individualized decisions making, where preventive measures could be carried out during the IVF/ICSI procedure and subsequent pregnancy.
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http://dx.doi.org/10.1186/s12958-020-00693-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789534PMC
January 2021

Clinical outcomes after single-versus double-embryo transfers in women with adenomyosis: a retrospective study.

Arch Gynecol Obstet 2021 Jan 2. Epub 2021 Jan 2.

Reproductive Medicine Center, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510655, China.

Background: Adenomyosis affects the outcomes of spontaneous fertility and assisted reproductive technology. The single blastocyst embryo transfer (SBT) policy is an effective strategy known to minimize the risk of multiple pregnancy for non-adenomyosis women. However, little is known about its applicability to women with adenomyosis. The purpose of this study is to compare pregnancy outcomes between SBT, double-blastocyst embryo transfer (DBT), single-cleavage-stage embryo transfer (SET) and double-cleavage-stage embryo transfer (DET) in the frozen-thawed embryo transfer cycles among adenomyosis patients.

Methods: This retrospective study was conducted in all frozen-thawed autologous embryo transfer cycles. 393 frozen-thawed embryo transfer cycles performed in adenomyosis patients were enrolled. The major clinical outcomes were implantation rate (IR), clinical pregnancy rate (CPR), miscarriage rate (MR), multiple pregnancy rate (MPR) and live birth rate (LBR).

Results:  The SBT and DBT groups achieved higher IR (P < 0.001), CPR (P = 0.017), LBR (P = 0.040) and lower MR (P = 0.020) than the SET and DET groups. But the SBT and DBT groups achieved similar CPR and LBR. The SBT and SET groups achieved lower MPR (P < 0.001) than the DBT and DET groups. The average birth weight (BW) of SBT groups was higher than the DBT and DET groups (P = 0.016). When compared with SBT group, low-birth-weight infants were significantly higher with DBT and DET.

Conclusions: When performing frozen-thawed embryo transfer cycles among adenomyosis patients, the SBT group has similar IR, CPR, MR, LBR but lower MPR compared to the DBT group. Therefore, SBT might be offered as standard practice.
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http://dx.doi.org/10.1007/s00404-020-05924-5DOI Listing
January 2021

Transferrin and antioxidants partly prevented mouse oocyte oxidative damage induced by exposure of cumulus-oocyte complexes to endometrioma fluid.

J Ovarian Res 2020 Nov 26;13(1):139. Epub 2020 Nov 26.

Center for Reproductive Medicine, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

Background: Exposure of oocytes to the endometrioma fluid has an adverse effect on embryonic quality. To determine whether adding transferrin and antioxidants to culture medium could counteract detrimental effects on mouse cumulus-oocyte complexes (COCs) induced by exposure to endometrioma fluid or not, we conducted an in vitro cross-sectional study using human and mouse COCs.

Methods: Eighteen women who had their oocytes exposed to endometrioma fluid during oocyte retrieval were enrolled. COCs from superovulated ICR female mice were collected. They were first exposed to human endometrioma fluid and then treated by transferrin and/or antioxidants (cysteamine + cystine). Subsequently, COCs function was assessed by molecular methods.

Results: This study observed that human COCs inadvertently exposed to endometrioma fluid in the in vitro fertilization (IVF) group led to a lower good quality embryo rate compared to intracytoplasmic sperm injection (ICSI) group. Exposure of mouse COCs to endometrioma fluid accelerated oocyte oxidative damage, evidenced by significantly reduced CCs viability, defective mitochondrial function, decreased GSH content and increased ROS level, associated with the significantly higher pro-portion of abnormal spindles and lower blastocyst formation (p < 0.05, respectively). This damage could be recovered partly by treating COCs with transferrin and antioxidants (cysteamine + cystine).

Conclusions: Transferrin and antioxidants could reduce the oxidative damage caused by COCs exposure to endometrioma fluid. This finding provides a promising new possibility for intervention in the human oocyte oxidative damage process induced by endometrioma fluid during oocyte pick-up.
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http://dx.doi.org/10.1186/s13048-020-00738-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690000PMC
November 2020

The prevalence of cervical insufficiency in Chinese women with polycystic ovary syndrome undergone ART treatment accompanied with negative prognosis: a retrospective study.

J Obstet Gynaecol 2020 Nov 24:1-5. Epub 2020 Nov 24.

Reproductive Medicine Center, The Six Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.

The objective of this study was to explore the correlation between cervical insufficiency (CI) and polycystic ovary syndrome (PCOS) in Chinese women undergoing assisted reproductive technology (ART) treatment. The retrospective study enrolled 2978 women including 1489 with PCOS and 1489 without PCOS, among which 34 women were diagnosed with CI (1.14%). The prevalence of CI in PCOS women was statistically higher than that in women without PCOS. Among those women with CI, 23 cases exhibited PCOS, and those cases had an average gestational age of 26.09 ± 5.91 weeks at the end of pregnancy, which was earlier than that of women without PCOS, and the pregnancy outcomes were worse than in the non-PCOS group though not statistically significant. Multivariable logistic regression showed that PCOS status (odds ratio: 2.050, 95% confidence interval: 1.009-4.206) were associated with increased risk of CI. Our study revealed that among those Chinese women who conceived by ART treatment, the prevalence of CI in women with PCOS was higher than that in women without PCOS. Co-morbidity of CI with polycystic ovarian syndrome negatively impacts prognosis.Impact statement Women with PCOS have a higher rate of adverse obstetrical outcomes than women without PCOS. Women with PCOS were more likely to have pregnancies complicated with CI. Co-morbidity of cervical incompetence with PCOS negatively impacts prognosis. Given these results, close surveillance of cervical changes during the second trimester in women with PCOS is necessary for reducing the risk of miscarriage related to CI.
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http://dx.doi.org/10.1080/01443615.2020.1819212DOI Listing
November 2020

The relationship between the oxidative stress reaction and the microbial community by a combinative method of PA and CCA.

Sci Total Environ 2021 Apr 16;763:143042. Epub 2020 Oct 16.

College of Resources and Environmental Science, Northeast Agricultural University, Harbin 150030, China. Electronic address:

Earthworms, as the first choice for soil monitoring and bio-remediation of cadmium (Cd)-contaminated soil, need to identify its mechanism under Cd stress. In this study, an artificial soil test method was used to determine the oxidative stress reaction indices, amino acid composition, and microbial community changes in earthworms under different stress durations and concentrations. For the first time, the canonical correlation analysis model and path analysis model were innovatively introduced into the data analysis to determine the mechanism that drives earthworm physiological functions after Cd stress. The results showed that in the low-stress concentration treatments (50-125 mg.kg DW), there was a driving relationship between oxidative stress reaction and microbial community in earthworm, and the driving factor was glycyl-L-glutamic acid at 50 mg.kg DW. With the increase of Cd stress intensity, the enzymes of oxidative stress promoted the survival microbes to begin to proliferate, and SOD became the main driving factor under 125 mg.kg DW Cd stress. In the high-stress concentration treatments (250-500 mg.kg DW), the driving effects were weakened or disappeared; while Cd-resistant microbial population appeared. This study provides a theoretical basis for the driving mechanism between oxidative stress effect and microbial community after Cd stress.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143042DOI Listing
April 2021

Granulosa cells apoptosis and follicular fluid hormones: comparison of progestin-primed ovarian stimulation versus GnRH antagonist protocols.

Gynecol Endocrinol 2020 Oct 23:1-5. Epub 2020 Oct 23.

Reproductive Medicine Research Center, Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China.

Objective: To explore the effect of progestin-primed ovarian stimulation protocol (PPOS) on mural granulosa cells (GCs) apoptosis and hormonal profiles in follicular fluid (FF) and efficacy over GnRH antagonist (GnRH-A) protocols.

Methods: We performed a prospective cohort study from June through August 2017 at a tertiary teaching hospital. 63 Patients meeting our criteria were recruited in this prospective study voluntarily and stratified to PPOS or GnRH-A group randomly. Mural GCs and FF were collected during oocyte retrieval. Apoptosis of GCs was assessed using the Annexin V-affinity assay by flow cytometry and hormonal profiles in FF were measured using electrochemiluminescence.

Results: A total of 63 women were assessed for eligibility, with 25 cases in PPOS group and 38 in GnRH-A group. Difference of early stage apoptosis rate, late stage apoptosis rate, and total apoptosis rate did not reach statistical significance between groups. Meanwhile, concentrations of hormones in FF were comparable in two groups. No statistically significant differences were observed in number of oocytes retrieved, mature oocyte rate, fertilization rate, and top-quality embryos rate. No patients experienced premature LH surge in both groups during the study.

Conclusion: Compared to GnRH antagonist protocol, PPOS had comparable laboratory outcomes, GCs apoptosis rate and hormonal profiles in FF. PPOS is an effective and safe alternative option to provide controlled ovarian hyperstimulation (COH).
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http://dx.doi.org/10.1080/09513590.2020.1822802DOI Listing
October 2020

Progress in deciphering trophoblast cell differentiation during human placentation.

Curr Opin Cell Biol 2020 12 18;67:86-91. Epub 2020 Sep 18.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; Innovation Academy for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

The maintenance of gestational well-being requires the proper development of both the embryo and the placenta. Placental trophoblast cells are the major building blocks of the developing placenta. Abnormal trophoblast differentiation underpins placental-based pregnancy complications. However, the mechanisms that govern trophoblast differentiation remain largely unclear. Recent studies shed light on several proteins and regulators that are involved in governing trophoblast differentiation. The advancement of new tools and novel technologies, such as the human trophoblast stem cell culture system, 3D placental organoids and single-cell multi-omics, has brought incredible insights to the field. Here we review the current literature, paying particular attention to articles published between 2017 and 2019 that have promoted our understanding of human trophoblast cell differentiation and its roles in pregnancy and its complications. At the same time, we address challenges and questions arising in the field of human placental development and disease.
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http://dx.doi.org/10.1016/j.ceb.2020.08.010DOI Listing
December 2020

Impact on using cryopreservation of testicular or epididymal sperm upon intracytoplasmic sperm injection outcome in men with obstructive azoospermia: a systematic review and meta-analysis.

J Assist Reprod Genet 2020 Nov 15;37(11):2643-2651. Epub 2020 Sep 15.

Reproductive Centre, The Sixth Affiliated Hospital, Sun Yat-sen University, No. 58 Zhong shan 2nd Rd., Yuexiu District, Guangzhou, 510080, China.

Purpose: To determine whether there was a significant impact on using cryopreservation of testicular or epididymal sperm upon the outcomes of intracytoplasmic sperm injection (ICSI) in patients with obstructive azoospermia (OA).

Method: Systematic review and meta-analysis of 20 retrospective studies in databases from January 1, 1995, to June 1, 2020.

Result: Twenty articles were included in this study. A total of 3602 (64.1%) of 5616 oocytes injected with fresh epididymal sperm were fertilized, compared with 2366 (61.2%) of 3862 oocytes injected with cryopreserved sperm (relative risk ratio (RR) 0.96, 95% confidence interval (CI) (0.90, 1.02), P > 0.05). A total of 303 (44.1%) of 687 ICSI cycles using fresh epididymal sperm resulted in a clinical pregnancy, compared with 150 (36.6%) of 410 ICSI cycles using cryopreserved epididymal sperm (RR 0.84, 95% CI (0.72, 0.97), P < 0.05). In the testis, a total of 2147 (68.7%) of 3125 oocytes injected with fresh sperm were fertilized, compared with 1623 (63.5%) of 2557 oocytes injected with cryopreserved sperm (RR 0.97, 95% CI (0.90, 1.06), P > 0.05). A total of 151 (47.8%) of 316 ICSI cycles using fresh testicular sperm resulted in a clinical pregnancy, compared with 113 (38.2%) of 296 ICSI cycles using cryopreserved sperm (RR 0.87, 95% CI (0.72, 1.05), P > 0.05).

Conclusions: In men with OA, there was a statistical lower clinical pregnancy rate (CPR) by using frozen epididymal sperm compared with fresh epididymal sperm, but showing no difference on fertilization rate (FR). Additionally, FR and CPR were not affected by whether the retrieved testicular sperm was frozen or fresh.
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http://dx.doi.org/10.1007/s10815-020-01940-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642125PMC
November 2020

A panel of extracellular vesicle long noncoding RNAs in seminal plasma for predicting testicular spermatozoa in nonobstructive azoospermia patients.

Hum Reprod 2020 11;35(11):2413-2427

Reproductive Medicine Center, The Sixth Affiliated Hospital, Sun Yat-sen University, 510655 Guangzhou, China.

Study Question: Whether the testis-specific extracellular vesicle (EV) long noncoding RNAs (lncRNAs) in seminal plasma could be utilized to predict the presence of testicular spermatozoa in nonobstructive azoospermia (NOA) patients?

Summary Answer: Our findings indicate that the panel based on seminal plasma EV lncRNAs was a sensitive and specific method in predicting the presence of testicular spermatozoa and may improve clinical decision-making of NOA.

What Is Known Already: The adoption of sperm retrieval techniques, especially microdissection testicular sperm extraction (mTESE), in combination with ICSI has revolutionized treatment for NOA. However, there are no precise and noninvasive methods for predicting whether there are testicular spermatozoa in NOA patients before mTESE.

Study Design, Size, Duration: RNA sequencing was performed on seminal plasma EVs from 6 normozoospermic men who underwent IVF due to female factor and 5 idiopathic NOA patients who failed to obtain testicular spermatozoa by mTESE and were diagnosed as having Sertoli cell-only syndrome by postoperative pathology. A biomarker panel of lncRNAs was constructed and verified in 96 NOA patients who underwent mTESE. Decision-making process was established based on the panel in seminal plasma EVs from 45 normozoospermia samples, 43 oligozoospermia samples, 62 cryptozoospermia samples, 96 NOA samples.

Participants/materials, Setting, Methods: RNA sequencing was done to examine altered profiles of EV lncRNAs in seminal plasma. Furthermore, a panel consisting of EV lncRNAs was established and evaluated in training set and validation sets.

Main Results And The Role Of Chance: A panel consisting of nine differentially expressed testis-specific lncRNAs, including LOC100505685, SPATA42, CCDC37-DT, GABRG3-AS1, LOC440934, LOC101929088 (XR_927561.2), LOC101929088 (XR_001745218.1), LINC00343 and LINC00301, was established in the training set and the AUC was 0.986. Furthermore, the AUC in the validation set was 0.960. Importantly, the panel had a unique advantage when compared with models based on serum hormones from the same group of NOA cases (AUC, 0.970 vs 0.723; 0.959 vs 0.687, respectively). According to the panel of lncRNAs, a decision-making process was established, that is when the score of an NOA case exceeds 0.532, sperm retrieval surgery may be recommended.

Limitations, Reasons For Caution: In the future, the sample size needs to be further expanded. Meanwhile, the regulatory functions and mechanism of lncRNAs in spermatogenesis also need to be elucidated.

Wider Implications Of The Findings: When the score of our panel is below 0.532, subjecting the NOA patients to ineffective surgical interventions may not be recommended due to poor sperm retrieval rate.

Study Funding/competing Interest(s): This work was supported by the National Natural Science Foundation of China (81871110, 81971314 and 81971759); the Guangdong Special Support Plan-Science and Technology Innovation Youth Top Talents Project (2016TQ03R444); the Science and Technology Planning Project of Guangdong Province (2016B030230001 and 201707010394); the Key Scientific and Technological Program of Guangzhou City (201604020189); the Pearl River S&T Nova Program of Guangzhou (201806010089); the Transformation of Scientific and Technological Achievements Project of Sun Yat-sen University (80000-18843235) and the Youth Teacher Training Project of Sun Yat-sen University (17ykpy68 and 18ykpy09). There are no competing interests related to this study.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deaa184DOI Listing
November 2020

Intrauterine infusion of platelet-rich plasma is a treatment method for patients with intrauterine adhesions after hysteroscopy.

Int J Gynaecol Obstet 2020 Dec 21;151(3):362-365. Epub 2020 Sep 21.

Reproductive Medicine Research Center, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Objective: To evaluate the efficacy of an intrauterine infusion of platelet-rich plasma (PRP) in patients with intrauterine adhesions (IUAs).

Methods: A retrospective study was conducted from April 2018 to December 2019 to compare the efficacy of intrauterine infusion of PRP with balloon for patients with IUAs. All patients had moderate or severe IUAs, including 28 patients with intrauterine infusion of PRP (group A), 22 patients with intrauterine balloon (group B), and 20 patients with both intrauterine infusion of PRP and balloon in the first operative hysteroscopy. American Fertility Society (AFS) score and rates of chemical pregnancy were compared.

Results: The AFS score decreased with an average of 5.18 ± 3.93, 4.91 ± 4.39, and 5.15 ± 3.17 comparing the third hysteroscopy with the first operative hysteroscopy in group A, group B, and group C, respectively. No significant differences were found among these groups (P=0.734). The rates of chemical pregnancy were 40.0% in group A, 38.9% in group B, and 33.3% in group C without significant differences (P=0.944).

Conclusion: There were no significant differences between intrauterine infusion of PRP and balloon. PRP is a treatment method for IUAs.
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http://dx.doi.org/10.1002/ijgo.13353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756367PMC
December 2020

In-house beam-splitting pulse compressor for high-energy petawatt lasers.

Opt Express 2020 Jul;28(15):22978-22991

One of the most significant bottlenecks in achieving kilojoule-level high-energy petawatt (PW) to hundreds-petawatt (100PW) lasers is the requirement of as large as meter-sized gratings so as to avoid the laser-induced damage in the compressor. High-quality meter-sized gratings have so far been difficult to manufacture. This paper proposes a new in-house (intra-) beam-splitting compressor based on the property that the damage threshold of gratings depends on the pulse duration. The proposed scheme will simultaneously improve the stability, save on expensive gratings, and simplify compressor size because the split beams share the first two parallel gratings. Furthermore, as the transmitted wavefront of a glass plate can be better and more precisely controlled than the diffraction wavefront of a large grating, we propose glass plates with designed transmitted wavefront to compensate for the wavefront distortion introduced by the second and third gratings, and other in-house optics, such as the beam splitter. This simple and economical method can compensate for the space-time distortion in the compressor, and thus improve focal intensity, which otherwise cannot be compensated by a deformable mirror outside the compressor. Together with a multi-beam tiled-aperture combining scheme, the proposed novel compressor provides a new scheme for achieving high-energy PW-100PW lasers or even exawatt lasers with relatively small gratings in the future.
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http://dx.doi.org/10.1364/OE.398668DOI Listing
July 2020

Mitochondrial DNA mutation exacerbates female reproductive aging via impairment of the NADH/NAD redox.

Aging Cell 2020 09 3;19(9):e13206. Epub 2020 Aug 3.

CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Hefei Institute of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.

Mammals' aging is correlated with the accumulation of somatic heteroplasmic mitochondrial DNA (mtDNA) mutations. Whether and how aging accumulated mtDNA mutations modulate fertility remains unknown. Here, we analyzed oocyte quality of young (≤30 years old) and elder (≥38 years old) female patients and show the elder group had lower blastocyst formation rate and more mtDNA point mutations in oocytes. To test the causal role of mtDNA point mutations on infertility, we used polymerase gamma (POLG) mutator mice. We show that mtDNA mutation levels inversely correlate with fertility, interestingly mainly affecting not male but female fertility. mtDNA mutations decrease female mice's fertility by reducing ovarian primordial and mature follicles. Mechanistically, accumulation of mtDNA mutations decreases fertility by impairing oocyte's NADH/NAD redox state, which could be rescued by nicotinamide mononucleotide treatment. For the first time, we answer the fundamental question of the causal effect of age-accumulated mtDNA mutations on fertility and its sex dependence, and show its distinct metabolic controlling mechanism.
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http://dx.doi.org/10.1111/acel.13206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511885PMC
September 2020

A prospective cohort study of home blood pressure monitoring based on an intelligent cloud platform (the HBPM-iCloud study): rationale and design.

Ther Adv Chronic Dis 2020 10;11:2040622320933108. Epub 2020 Jun 10.

Department of Cardiology, Shunde hospital, Southern Medical University, Jiazi Road 1, Lunjiao Town, Shunde District, Foshan, Guangdong 523808, China The George Institute for Global Health, NSW 2042 Australia.

Background: Hypertension, as a predominant risk factor for cardiovascular disease, is a severe public health burden in China. Home blood pressure monitoring (HBPM) is an important tool in the detection and management of hypertension. However, there is a lack of HBPM data from prospective cohorts in China. Hence, we designed this study to investigate the impact of HBPM on major health outcomes in Chinese population participating in regular health check-ups.

Methods: Leveraging telemedicine technology, the open prospective, multicenter, HBPM-iCloud (Home Blood Pressure Monitoring Based on an Intelligent Cloud Platform) cohort study will recruit participants from three participating health check-up centers in southern China to participate in cloud-based HBPM for 1 week. The prevalence of sustained hypertension, white coat hypertension (WCH), masked hypertension (MH), white coat uncontrolled hypertension (WUCH), and masked uncontrolled hypertension (MUCH) will be defined by a combination of average readings of home-based and office-based blood pressure (BP). Cardiovascular risk factors and subclinical target organ damage will be recorded. Participants will be followed-up for 5 years to examine the incidence and associated risk factors of composite major adverse cardiovascular and cerebrovascular event.

Conclusion: The study will help to determine the best way to implement telemedicine technology in BP control for better prevention and treatment of hypertension. Results will provide data for a Chinese population to aid in the construction of screening, risk stratification, and intervention strategies for abnormal BP phenotypes, including WCH, MH, WUCH, and MUCH.
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http://dx.doi.org/10.1177/2040622320933108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288800PMC
June 2020

Wavelength shift with a diode-pumped continuous-wave Yb:CALGO laser.

Appl Opt 2020 Mar;59(7):2097-2100

The dependence of an emission wavelength on the crystal temperature was first investigated for a diode-pumped continuous-wave ${{\rm Yb}^{3 + }}$Yb-doped ${{\rm CaGdAlO}_4}$CaGdAlO (Yb:CALGO) laser. A maximum output power of 11 W was obtained, corresponding to a slope efficiency of 19.8%. The output wavelength varied from 1051.10 nm to 1054.72 nm with increased absorbed pump power. This wavelength shift is attributed to a change in the crystal temperature. This observation is, to our best knowledge, an original conclusion about this phenomenon in a Yb:CALGO laser. We use a temperature-dependent model to explain the emission wavelength shifts that can be generalized to any such quasi-three-level materials.
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http://dx.doi.org/10.1364/AO.385337DOI Listing
March 2020

Mild stimulation protocol vs conventional controlled ovarian stimulation protocol in poor ovarian response patients: a prospective randomized controlled trial.

Arch Gynecol Obstet 2020 05 24;301(5):1331-1339. Epub 2020 Mar 24.

Reproductive Medicine Research Center, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510655, China.

Purpose: To compare the efficacy of mild ovarian stimulation protocol and conventional controlled ovarian stimulation (COS) protocol for poor ovarian response (POR) patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).

Methods: This single-center prospective randomized controlled trial conducted from September 2013 to September 2015, including 191 patients who met the Bologna criteria of POR. Ninety-seven patients allocated to the mild ovarian stimulation group (MS group) were stimulated according to the letrozole/antagonist protocol, while 94 patients in the controlled ovarian stimulation group (COS group) were stimulated according to a high dose of gonadotropin (Gn) combined with gonadotropin-releasing hormone agonist (GnRH-a) stop protocol. The cumulative live birth rate was the primary outcome. Chinese clinical trial number ChiCTR-TRC-13003454.

Results: Comparing with the COS group, both the stimulation duration and the total gonadotropin dose were significantly shorter and lower in the MS group (P < 0.001). A higher number of retrieved oocytes (P = 0.003) and transferrable embryos (P = 0.029) were obtained in the COS group. The cumulative live birth rates (OR 1.103; 95% CI 0.53 to 2.28; P = 0.791) were comparable between the two groups.

Conclusions: The increase of Gn dose during ovulation stimulation was associated with a higher number of transferrable embryos for POR patients, but this increase did not lead to a concomitant improvement of reproductive outcome, especially in terms of the cumulative live birth rate. Using a mild stimulation protocol was economically preferential while it was as effective as higher doses of Gn stimulation protocol in reproductive outcome for POR patients.
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http://dx.doi.org/10.1007/s00404-020-05513-6DOI Listing
May 2020

Inhibiting Necroptosis of Spermatogonial Stem Cell as a Novel Strategy for Male Fertility Preservation.

Stem Cells Dev 2020 04 9;29(8):475-487. Epub 2020 Mar 9.

Reproductive Centre, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Fertility preservation is a common concern for male cancer survivors of reproductive age. However, except for testicular tissue cryopreservation, which is not very effective, there is no feasible and precise therapy capable of protecting spermatogenesis for prepubertal boys before or during gonadotoxic treatment. This study aims to investigate the effects of inhibiting necroptosis of spermatogonial stem cell (SSC) in fertility preservation. Male mice 12 weeks of age were used to establish gonadotoxicity with two intraperitoneal injections of busulfan at a total dose of 40 mg kg. The mouse model and the primary cultured mouse SSCs were used to characterize the relationship between necroptosis of SSC and gonadotoxicity. Meanwhile, the effects of an inhibitor of necroptosis pathway, RIPA-56, were observed on day 36 in the mouse model of busulfan-induced gonadotoxicity. We found that the number of SSCs was decreased, but the level of necroptosis was upregulated on day 18 after busulfan treatment in testes from gonadotoxic mice. Further experiments in primary cultured cells showed that the necroptosis caused cell death in busulfan-treated SSCs and could be inhibited by RIPA-56. After suppressing the necroptosis of SSCs, the busulfan-induced mice had a decreased loss of spermatogenic cells as shown by histology and an increased Johnsen's score. Moreover, the quantities of SSCs and epididymal spermatozoa were restored after intervention with RIPA-56, indicating a series of beneficial effects by targeting the necroptosis of SSCs in mice undergoing busulfan treatment. In conclusion, our findings reveal that the necroptosis of SSCs plays a critical role in busulfan-induced gonadotoxicity and may be a potential target for male fertility preservation.
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http://dx.doi.org/10.1089/scd.2019.0220DOI Listing
April 2020

FOXO4-DRI alleviates age-related testosterone secretion insufficiency by targeting senescent Leydig cells in aged mice.

Aging (Albany NY) 2020 01 20;12(2):1272-1284. Epub 2020 Jan 20.

Reproductive Medicine Research Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China.

Male late-onset hypogonadism is an age-related disease, the core mechanism of which is dysfunction of senescent Leydig cells. Recent studies have shown that elimination of senescent cells can restore proper homeostasis to aging tissue. In the present study, we found that the fork head box O (FOXO) transcription factor FOXO4 was specially expressed in human Leydig cells and that its translocation to the nucleus in the elderly was related to decreased testosterone synthesis. Using hydrogen peroxide-induced senescent TM3 Leydig cells as an model, we observed that FOXO4 maintains the viability of senescent Leydig cells and suppresses their apoptosis. By disrupting the FOXO4-p53 interaction, FOXO4-DRI, a specific FOXO4 blocker, selectively induced p53 nuclear exclusion and apoptosis in senescent Leydig cells. In naturally aged mice, FOXO4-DRI improved the testicular microenvironment and alleviated age-related testosterone secretion insufficiency. These findings reveal the therapeutic potential of FOXO4-DRI for the treatment of male late-onset hypogonadism.
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http://dx.doi.org/10.18632/aging.102682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053614PMC
January 2020

Thermosensitive Hydrogel Based on Poly(2-Ethyl-2-Oxazoline)-Poly(D,L-Lactide)-Poly(2-Ethyl-2-Oxazoline) for Sustained Salmon Calcitonin Delivery.

AAPS PharmSciTech 2020 Jan 17;21(2):71. Epub 2020 Jan 17.

College of Pharmacy, Xi'an Medical University, Xi'an, 710072, Shaanxi, People's Republic of China.

This study developed a thermosensitive hydrogel based on poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)-poly(2-ethyl-2-oxazoline) (PPP) for the delivery of salmon calcitonin to improve the hypocalcemic effect. The tube inversion and rheological tests revealed that the copolymer solution underwent temperature-dependent sol-gel-sol transitions. Observation by scanning electron microscopy (SEM) showed that the hydrogel exhibited a porous three-dimensional network. The swelling test demonstrated that there was a maximum swelling ratio at low temperature (25°C) as compared with the high temperature (37°C). In vitro release revealed that the PPP hydrogel were capable of sustained release of salmon calcitonin (sCT). The in vivo biodegradability study indicated the good degradability of PPP hydrogel. More importantly, the in vivo retention time of the hydrogel in situ was significantly prolonged after subcutaneous injection of the PPP hydrogel compared to the F127 hydrogel. In vivo pharmacodynamics analysis showed that the hypocalcemic effect of both PPP and F127 hydrogel was significantly greater than that of sCT solution, and the mean serum Ca reduction effect could be maintained for 24 h of PPP hydrogel, indicating that PPP hydrogel could achieve a significant enhanced hypocalcemic effect. In conclusion, the PPP hydrogel has been shown to be prospective as a controlled release carrier for injection delivery of protein drugs.
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http://dx.doi.org/10.1208/s12249-020-1619-1DOI Listing
January 2020

Natural variation of an EF-hand Ca-binding-protein coding gene confers saline-alkaline tolerance in maize.

Nat Commun 2020 01 10;11(1):186. Epub 2020 Jan 10.

State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing, 100094, China.

Sodium (Na) toxicity is one of the major damages imposed on crops by saline-alkaline stress. Here we show that natural maize inbred lines display substantial variations in shoot Na contents and saline-alkaline (NaHCO) tolerance, and reveal that ZmNSA1 (Na Content under Saline-Alkaline Condition) confers shoot Na variations under NaHCO condition by a genome-wide association study. Lacking of ZmNSA1 promotes shoot Na homeostasis by increasing root Na efflux. A naturally occurred 4-bp deletion decreases the translation efficiency of ZmNSA1 mRNA, thus promotes Na homeostasis. We further show that, under saline-alkaline condition, Ca binds to the EF-hand domain of ZmNSA1 then triggers its degradation via 26S proteasome, which in turn increases the transcripts levels of PM-H-ATPases (MHA2 and MHA4), and consequently enhances SOS1 Na/H antiporter-mediated root Na efflux. Our studies reveal the mechanism of Ca-triggered saline-alkaline tolerance and provide an important gene target for breeding saline-alkaline tolerant maize varieties.
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http://dx.doi.org/10.1038/s41467-019-14027-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954252PMC
January 2020

A HAK family Na transporter confers natural variation of salt tolerance in maize.

Nat Plants 2019 12 9;5(12):1297-1308. Epub 2019 Dec 9.

State Key Laboratory of Plant Physiology and Biochemistry, College of Biological Sciences, China Agricultural University, Beijing, China.

Excessive sodium ion (Na) concentrations in cultivated land alter crop yield and quality worldwide. Previous studies have shown that shoot Na exclusion is essential in most crops for salt tolerance. Here, we show by a genome-wide association study that Zea may L. Na content 2 (ZmNC2), encoding the HAK family ion transporter ZmHAK4, confers the natural variation of shoot Na exclusion and salt tolerance in maize. The ZmHAK4 locus accounts for ~11% of the shoot Na variation, and a natural ZmHAK4-deficient allele displays a decreased ZmHAK4 expression level and an increased shoot Na content. ZmHAK4 is preferentially expressed in the root stele and encodes a novel membrane-localized Na-selective transporter that mediates shoot Na exclusion, probably by retrieving Na from xylem sap. ZmHAK4 orthologues were identified in other plant species, and the orthologues of ZmHAK4 in rice and wheat show identical expression patterns and ion transport properties, suggesting that ZmHAK4 orthologues mediate an evolutionarily conserved salt-tolerance mechanism. Finally, we show that ZmHAK4 and ZmHKT1 (a HKT1 family Na-selective transporter) confer distinct roles in promoting shoot Na exclusion and salt tolerance, indicating that the combination of the favourable alleles of ZmHKT1 and ZmHAK4 can facilitate the development of salt-tolerant maize varieties.
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http://dx.doi.org/10.1038/s41477-019-0565-yDOI Listing
December 2019

Correction to: Endometrium metabolomic profiling reveals potential biomarkers for diagnosis of endometriosis at minimal-mild stages.

Reprod Biol Endocrinol 2019 11 6;17(1):89. Epub 2019 Nov 6.

School of Pharmaceutical Sciences in Sun Yat-sen University, 132# Waihuandong Road, Guangzhou, University City, Guangzhou, 510006, People's Republic of China.

The authors regret that the incorrect identification of "omega-3 arachidonic acid" published in the original manuscript [1].
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http://dx.doi.org/10.1186/s12958-019-0532-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833161PMC
November 2019

Transplantation of Human Urine-Derived Stem Cells Ameliorates Erectile Function and Cavernosal Endothelial Function by Promoting Autophagy of Corpus Cavernosal Endothelial Cells in Diabetic Erectile Dysfunction Rats.

Stem Cells Int 2019 9;2019:2168709. Epub 2019 Sep 9.

Reproductive Medicine Research Center, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China.

Aims: Cavernosal endothelial dysfunction is one of the factors in developing diabetic erectile dysfunction (DED), but the mechanism of cavernosal endothelial dysfunction is unclear. The present study is aimed at determining the contribution of autophagy in cavernosal endothelial dysfunction of DED rats and explaining the therapeutic effect of urine-derived stem cells (USCs).

Methods: After rat corpus cavernosal vascular endothelial cells (CCECs) were isolated and cultured , CCECs were treated with advanced glycation end products (AGEs) to mimic the diabetic situation. Autophagy flux, proliferation, and apoptosis of CCECs were determined by mRFP-GFP-LC3 adenovirus infection combined with fluorescence observation and western blot analysis. USCs were isolated from the urine of six healthy male donors, and coculture systems of USCs and CCECs were developed to assess the protective effect of USCs for CCECs . The contribution of autophagy to the cellular damage in CCECs was evaluated by the autophagic inhibitor, 3-methyladenine (3-MA). Then, DED rats were induced by streptozotocin (50 mg/kg) and screened by apomorphine test (100 g/kg). In DED rats, USCs or PBS as vehicle was administrated by intracavernous injection ( = 15 per group), and another 15 normal rats served as normal controls. Four weeks after injection, erectile function was evaluated by measuring the intracavernosal pressure (ICP) and mean arterial pressure (MAP). Cavernosal endothelial function and autophagic activity were examined by western blot, immunofluorescence, and transmission electron microscopy.

Results: , AGE-treated CCECs displayed fewer LC3 puncta formation and expressed less LC3-II, Beclin1, and PCNA but expressed more p62 and cleaved-caspase3 than controls ( < 0.05). Coculture of USCs with CCECs demonstrated that USCs were able to protect CCECs from AGE-induced autophagic dysfunction and cellular damage, which could be abolished by 3-MA ( < 0.05). DED rats showed lower ratio of ICP/MAP, reduced expression of endothelial markers, and fewer autophagic vacuoles in the cavernosal endothelium when compared with normal rats ( < 0.05). Intracavernous injection of USCs improved erectile function and cavernosal endothelial function of DED rats ( < 0.05). Most importantly, our data showed that the repaired erectile function and cavernosal endothelial function were the result of restored autophagic activity of the cavernosal endothelium in DED rats ( < 0.05).

Conclusions: Impaired autophagy is involved in the cavernosal endothelial dysfunction and erectile dysfunction of DED rats. Intracavernous injection of USCs upregulates autophagic activity in the cavernosal endothelium, contributing to ameliorating cavernosal endothelial dysfunction and finally improving the erectile dysfunction induced by diabetes.
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http://dx.doi.org/10.1155/2019/2168709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754951PMC
September 2019