4-Phenylbutyric acid may prevent mouse ovarian and uterine damage due to procymidone-induced alteration of circRNA Scar and circZc3h4 levels by controlling excessive unfolded protein response.

Procymidone (PCM) below the no-observed-adverse-effect-level (NOAEL) has previously been proven to induce ovarian and uterine damage in adolescent mice due to its raised circRNA Scar, decreased circZc3h4, and overactivated unfolded protein response (UPR). Also, 4-phenylbutyric acid (4-PBA) inhibits histone deacetylase and endoplasmic reticulum stress, reduces UPR, improves metabolism, and ensures homeostasis within the endoplasmic reticulum. In this study, 20, 40 and 80 mM of 4-PBA were utilized respectively to intervene the damage caused by 1.0 × 10-5 M PCM to ovaries and uterus in vitro culture. Besides, 100 mg/kg /d 4-PBA was intraperitoneally injected to female adolescent mice before, during and after oral administration of 100 mg/kg /d PCM for prevention and cure to observe tissue changes in the ovaries and uteri, and levels of circRNA Scar, circZc3h4 and UPR members. Our findings demonstrated that in vitro experiments, all doses of 4-PBA could inhibit ovarian and uterine damage caused by PCM, and the effect of 80 mM was especially noticeable. In the in vivo experiments, the best results were obtained when PCM was given with simultaneous 4-PBA intervention, i.e., minimal ovarian and uterine damage. Both in vivo and in vitro, 4-PBA in the ovary and uterus resulted in decreased circRNA Scar levels, increased circZc3h4 abundance, and moderately elevated levels of UPR members. So, it is suggested that 4-PBA moderately activates UPR, partially or completely antagonizing the elevated circRNA Scar and decreased circZc3h4 and consequently preventing PCM-induced ovarian and uterine damage effectively in adolescent mice.

Reduction of excessive unfolded protein response by 4-phenylbutyric acid may mitigate procymidone-induced testicular damage in mice by changing the levels of circRNA Scar and circZc3h4.

Procymidone (PCM) exposure below the no-observed-effect level triggers changes in circRNA Scar and circZc3h4 and overactivation of the unfolded protein response (UPR) in mice, culminating in testicular injury. The 4-phenyl butyric acid (4-PBA) is known to stabilize proteins and reduce the UPR. This study employed an in vitro system in which mouse testes were cultured with 1 × 10-5 M PCM and varying concentrations (0, 20, 40, and 80 mM) of 4-PBA; 4-week-old male mice were subsequently treated with 100 mg/kg/d PCM (suspended in corn oil) and/or 100 mg/kg/d 4-PBA for 21 d, consecutively. The treatments were as follows: the negative control (NC) group was orally administered corn oil; the positive control (PC) group was orally administered PCM; the 4-PBA group was intraperitoneally injected with 4-PBA; the 4-PBA-I group was orally administered PCM and 4-PBA simultaneously; the 4-PBA-II group received daily administration of 4-PBA 24 h prior to PCM; and the 4-PBA-III group was intraperitoneally injected with 4-PBA for 7 d after 21 d of PCM administration. However, the 4-PBA intervention groups showed no considerable changes in the overall or testicular appearance of mice. In vitro, 4-PBA inhibited the PCM-induced testicular injury, with the most significant effect observed at 80 mM. In vivo, the 4-PBA-III group exhibited the best in vivo effects. Our findings indicate that 4-PBA conferred testicular protection by decreasing PCM-induced circRNA Scar, elevating circZc3h4, and suppressing UPR both in vitro and in vivo. It has been hypothesized that 4-PBA mitigates testicular damage by reducing excessive UPR levels.

Rapidity and Energy Dependencies of Temperatures and Volume Extracted from Identified Charged Hadron Spectra in Proton-Proton Collisions at a Super Proton Synchrotron (SPS).

The standard (Bose-Einstein/Fermi-Dirac, or Maxwell-Boltzmann) distribution from the relativistic ideal gas model is used to study the transverse momentum (pT) spectra of identified charged hadrons (π-, π+, K-, K+, p¯, and p) with different rapidities produced in inelastic proton-proton (pp) collisions at a Super Proton Synchrotron (SPS). The experimental data measured using the NA61/SHINE Collaboration at the center-of-mass (c.m.) energies s=6.3, 7.7, 8.8, 12.3, and 17.3 GeV are fitted well with the distribution. It is shown that the effective temperature (Teff or T), kinetic freeze-out temperature (T0), and initial temperature (Ti) decrease with the increase in rapidity and increase with the increase in c.m. energy. The kinetic freeze-out volume (V) extracted from the π-, π+, K-, K+, and p¯ spectra decreases with the rapidity and increase with the c.m. energy. The opposite tendency of V, extracted from the p spectra, is observed to be increasing with the rapidity and decreasing with the c.m. energy due to the effect of leading protons.

[Change of the retinoic acid pathway in hypothalamus and pituitary damage induced by combined exposure to low-level Pb~(2+) and 1-nitropyrene in mice].

OBJECTIVE: To observe the expression of the retinoic acid(RA) pathway in hypothalamus and pituitary damage induced by combined exposure of low-level lead and 1-nitropyrene in mice, and to explore the relationship between the changes of RA pathway and hypothalamus and pituitary damage. METHODS: A total of 84 4-week-old ICR mice were randomly divided into the control group, Pb~(2+) tainted group(0.008 mg/L), 1-NP tainted group(0.1 mg/kg), low(0.008 mg/L Pb~(2+)+0.004 mg/kg 1-NP), medium(0.008 mg/L Pb~(2+)+0.02 mg/kg 1-NP), and high-dose co-toxicity group(0.008 mg/L Pb~(2+)+0.1 mg/kg 1-NP) according to body weight, with 14 mice in each group. Among them, Pb~(2+) was provided by lead acetate, added to deionized water and ingested by mice drinking freely, 1-NP was given by intraperitoneal injection, 1-NP was administered by intraperitoneal injection. Record daily water intake and food intake. After 21 consecutive days of exposure, body mass was measured, histological changes in the hypothalamus and pituitary were observed under an optical microscope, and lead content in brain tissue was measured by atomic absorption spectrometry. The real-time fluorescence quantitative PCR was used to detect the abundance of retinoic acid pathway members and c-Jun N-terminal kinases genes(Jnks), and the western blot method was used to detect expression levels of acetaldehyde dehydrogenase 2(ALDH2), cytochrome P450 family member 26A1(CYP26a1) proteins. RESULTS: There was no difference in the mean weekly water intake and food intake of the mice in each group. The body weight of the high-dose co-toxicity group mice((27.4±1.9)g) was lower than that of the control group((29.8±2.3)g)(P<0.05). The level of serum follicle-stimulating hormone(FSH) in the middle and high dose co-toxicity groups((265.01±2.99), (260.42±3.61)pg/mL, respectively) was lower than that in the control group((279.00±1.30)pg/mL, P<0.05). The content of Pb~(2+) in the brain of each group containing Pb~(2+) was higher than that of the control group. In the hypothalamic and pituitary tissues, the abundance of Adh1, Adh2, Rar and Rxr, and ALDH2 levels in the medium and high dose co-toxicity groups were higher than those in the control group(P<0.05). Cyp26a1 gene abundance and protein levels were lower in the medium and high dose co-toxicity groups than in the control group(P<0.05). The abundance of Jnks in the high-dose co-toxicity group was higher than that in the control group(P<0.05). CONCLUSION: Continuous exposure to 0.008 mg/L Pb~(2+)+0.1 mg/kg 1-NP for 21 days can cause damage to the hypothalamus and pituitary of mice, and activate the RA signaling pathway.

Combined effect of unfolded protein response and circZc3h4, circRNA Scar in mouse ovary and uterus damage induced by procymidone.

Procymidone (PCM) is a fungicide commonly used to prevent and control plant diseases, and it is also an environmental endocrine disruptor that has a typical anti-androgen effect on the function and/or structure of the vertebrate reproductive system. The activation of the unfolded protein response (UPR) will fold the protein correctly to ensure the cell's survival. PCM regulates GRP78 by affecting the level of hormones, and there is a regulatory relationship between the UPR, the circRNAs and the miRNAs. In vivo experiments, PCM (suspended in soybean oil) was orally administered to adolescent female mice for 21 days in 3 different doses of 50 mg kg-1 day-1 (low dose), 100 mg kg-1 day-1 (medium dose) and 200 mg kg-1 day-1 (high dose) to cause ovaries and uteruses damage, and in vitro experiments, various doses of PCM from 0.33 × 10-5 (low dose) to 1 × 10-5 (medium dose) then 3 × 10-5 M (high dose) were used to induce injury on the ovaries and uteri of the mice. We found out that both in vivo and in vitro, PCM caused dose-dependent damages to the ovaries and uteri, increased their circRNA Scar levels and decreased circZc3h4 abundance. Also, all UPR signaling pathways in the low-dose group and some in the middle-dose group were activated. It is speculated that UPR may antagonize the partial ovarian and uterine damage in adolescent mice induced by PCM at doses less than NOAEL via changes in circZc3h4 and circRNA Scar.

The joint action of unfolded protein response, circZc3h4, and circRNA Scar in procymidone-induced testicular injury in adolescent mice.

Procymidone (PCM) is a low toxicity fungicide, and an endocrine-disrupting chemical (EDC) that particularly damages the reproductive system of male vertebrates. In present study, adolescent mice in control, low-, medium-, and high-dose groups were orally administered 0 (equal volume of soybean oil), 50, 100, and 200 mg/kg/day PCM, respectively, for 21 days. Additionally, a three-dimensional culture of mouse testes was performed in vitro, and the control, low dose (0.33 × 10-5  M), medium dose (1 × 10-5  M), and high dose (3 × 10-5  M) PCM groups were established. We have found that, under both in vivo and in vitro conditions, all doses of PCM caused damage to mouse testes. Moreover, the levels of circZc3h4 RNA and Zc3h4 decreased while miR-212 increased in all treatment groups, with a corresponding rise in circRNA Scar and fall in Atp5b, compared to those in the control group, and all the changes showed a dose-response relationship. Besides, we have identified that low doses of PCM could activate the Ire1-Xbp1 pathway, whereas the medium and high doses activated the Perk-Elf2α-Atf4, Ire1-Xbp1, and Atf6 pathways. And it is, therefore, speculated that the unfolded protein response (UPR), circZc3h4 and circRNA Scar may have taken joint action in testicular injury in adolescent mice induced by PCM at the no observed adverse effect level (NOAEL, 100 mg/kg/day) and below NOAEL doses.

Flutamide induces uterus and ovary damage in the mouse via apoptosis and excessive autophagy of cells following triggering of the unfolded protein response.

Intrauterine exposure to flutamide not only causes abnormal development of the reproductive organs in male offspring, but also damages ovaries and uteri. The unfolded protein response (UPR) is believed to play an important role in embryo development and teratogenic processes. In the present study, pregnant mice were administered either flutamide (300mg kg-1 day-1, p.o.) on an equivalent volume of soybean oil (control) on Days 12-18 of gestation. Eight weeks after birth, female offspring in the flutamide-treated group had a lower bodyweight and lower ovarian and uterine weights, but there was no significant difference in uterine and ovarian weights normalised by bodyweight between the flutamide-treated and control groups. Furthermore, histopathological changes were observed in all uteri and ovaries in the flutamide-treated group, with fewer and less-developed follicles in the ovaries. In both the uteri and ovaries, flutamide increased the expression of UPR members, although the expression of cell cycle-related genes remained unchanged compared with the control group. Flutamide increased the expression of all autophagy- and apoptosis-related genes evaluated in the uterus, as well as some in the ovary. The results suggest that the in utero exposure of mice to flutamide may contribute to uterine and ovarian damage in the offspring, with endoplasmic reticulum stress possibly triggered by the UPR leading to the induction of excessive autophagy and apoptosis.

Analyzing Transverse Momentum Spectra of Pions, Kaons and Protons in p-p, p-A and A-A Collisions via the Blast-Wave Model with Fluctuations.

The transverse momentum spectra of different types of particles, π±, K±, p and p¯, produced at mid-(pseudo)rapidity in different centrality lead-lead (Pb-Pb) collisions at 2.76 TeV; proton-lead (p-Pb) collisions at 5.02 TeV; xenon-xenon (Xe-Xe) collisions at 5.44 TeV; and proton-proton (p-p) collisions at 0.9, 2.76, 5.02, 7 and 13 TeV, were analyzed by the blast-wave model with fluctuations. With the experimental data measured by the ALICE and CMS Collaborations at the Large Hadron Collider (LHC), the kinetic freeze-out temperature, transverse flow velocity and proper time were extracted from fitting the transverse momentum spectra. In nucleus-nucleus (A-A) and proton-nucleus (p-A) collisions, the three parameters decrease with the decrease of event centrality from central to peripheral, indicating higher degrees of excitation, quicker expansion velocities and longer evolution times for central collisions. In p-p collisions, the kinetic freeze-out temperature is nearly invariant with the increase of energy, though the transverse flow velocity and proper time increase slightly, in the considered energy range.

Excitation Functions of Tsallis-Like Parameters in High-Energy Nucleus-Nucleus Collisions.

The transverse momentum spectra of charged pions, kaons, and protons produced at mid-rapidity in central nucleus-nucleus (AA) collisions at high energies are analyzed by considering particles to be created from two participant partons, which are assumed to be contributors from the collision system. Each participant (contributor) parton is assumed to contribute to the transverse momentum by a Tsallis-like function. The contributions of the two participant partons are regarded as the two components of transverse momentum of the identified particle. The experimental data measured in high-energy AA collisions by international collaborations are studied. The excitation functions of kinetic freeze-out temperature and transverse flow velocity are extracted. The two parameters increase quickly from ≈3 to ≈10 GeV (exactly from 2.7 to 7.7 GeV) and then slowly at above 10 GeV with the increase of collision energy. In particular, there is a plateau from near 10 GeV to 200 GeV in the excitation function of kinetic freeze-out temperature.

[Expression of retinoic acid signaling pathway in uterus injury induced by procymidone in adolescent mice].

OBJECTIVE: To investigate the expression of key genes and proteins of retinoic acid signaling pathway in procymidone-induced uterine injury in adolescent mice, and analyze the relationship between the signaling pathway and female reproductive damage. METHODS: The 3-week age ICR mice were randomly divided into low, medium, and high-dose groups and one control group with 8 mice in each group by weight. The low, medium and high dose groups were respectively given 50, 100 and 200 mg/(kg·d) procymidone orally for 21 days continuously, while the control group was given equal volume of soybean oil. After the mice were sacrificed, the uterus was taken from both sides for observing the histological changes in the cross-sectional slices of the uterus, the detection of the expression abundance of genes which related to the retinoic acid signaling pathway by the real-time fluorescent quantitative PCR, and the measurement of ALDH2 and CYP26 a1 proteins expression by Western blot. RESULTS: The body weight of mice in low-dose, medium-dose and high-dose groups were(27.50±1.49) g, (27.72±1.40) g and(26.89±1.19) g, respectively, which were lower than those in control group(31.48±1.14) g(P<0.05). The density of uterine lining monolayer columnar epithelium and lamina propria tubular uterine glands gradually decreases, at the same time the uterine folds become less with the dose of procymidone increases. adh1, ad/2, aldh1a1 in each experimental group were higher than those in the control group(P<0.05); the expression levels of aldh1a2 and aldh1a3 genes in the middle and high dose groups were higher than those in the control group(P<0.05); the expression levels of retinoic acid nuclear receptor rarα, rarγ, rxrα and rxrß genes in the high-dose group were higher than those in the control(P<0.05); yet the expression levels of cyp26a2 and cyp26a3 in the high-dose group were lower than those in the control group(P<0.05); the jnk family in medium and high dose groups were higher than the control(P<0.05). The expression of ALDH2 in each experimental group was higher than that in the control group, and increased with the increase of the dose(P<0.05); the expression of CYP26 a1 in each experimental group was not significantly different from that of the control group. CONCLUSION: The retinoic acid signal pathway is activated in procymidone-induced uterine injury in mice, then regulates the increase of the expression of jnk family, leading to the damage.

[Injury of procymidone on testis and sperm in the male adolescent mice].

OBJECTIVE: To investigate the damage of procymidone to penile, testis and sperm in adolescent male mice. METHODS: 4-week-old male ICR mice were allocated randomly to the treatment groups and the control group, with 8 mice in each group. Procymidone was administered to mice by gavage with dose 50 mg/kg(low dose), 100 mg/kg and 200 mg/kg, while the control group was given only an equal volume of soybean oil. On the 11 th days, the mice were sacrificed by spinal dislocation, their body masses were weighed, and the anogenital distance(AGD), testicular volume and penis length were measured. Furthermore the weight of the testes, epididymis and penis were weighed, the organ coefficients were calculated, and then a testis on one side and 1/2 penis tissue were fixed in 4% paraformaldehyde and used for histology analysis. The testis on the other side and the remaining 1/2 penis were used to detect androgen content and Caspase-3, Caspase-9, Caspase-12 and Bax gene expression. At the same time, one epididymis was randomly selected to detect sperm motility, density and morphology. RESULTS: The weight, penis length and testicular volume of mice in each experimental group did not change significantly, while the weight of testes and epididymis and testicular and epididymal coefficients of mice in the high-dose group decreased significantly(P<0. 05). The testis seminiferous tubules of every treatment group showed different degrees of degeneration, spermatogenic cell damage, and decreased number of luminal sperm. Meanwhile, medium and high dose treatment groups showed hyperplasia of testicular stromal cells. However, there was no significant pathologic change in penile tissue in every treatment group. The sperm density of mice in the middle and high dose groups was lower than that of the control group(P<0. 05), and the sperm deformity rate in the two groups was significantly higher than that of the control group(P<0. 01), while the sperm motility of every dose treatment group was lower than that of the control(P<0. 05). The testosterone in the testis of the middle and high dose groups were high than the control(P<0. 001), while there was no statistically significant difference of the testosterone among all the groups in the penis(P>0. 05). In addition, the expression of pro-apoptotic genes Caspase-3, Caspase-9, Caspase-12 and Bax in testis tissues of the high-dose group were significantly increased(P<0. 05). CONCLUSION: Procymidone can cause damage to the structure and function of testes, reduce sperm quality, and increase the expression of certain pro-apoptotic genes in adolescent male mice.

[Role of Hippo signaling pathway in mice hypospadias induced by vinclozolin].

OBJECTIVE: To observe the role of Hippo signaling pathway in mice hypospadias induced by vinclozolin. METHODS: After 8 weeks of ICR mice were conceived, they were divided randomly into the treatment and the control groups(10 for each group). Vinclozolin was orally administraed to the pregnant mice in the treatment group with 400 mg/(kg·d) during gestation days 12-18, while those of the control group were treated with equal volume of soybean oil. About 60 days after birth, 20 penises of the mouse offspring were taken randomly from both of the two groups separately. And furthermore, the relative expression abundance of Hippo signaling pathway key genes(Mst1, Lats1, Taz, Yap), androgen receptor gene Ar of all the samples were measured by the real-time quantity reverse transcript polymerase chain reaction(qPCR). The Yes-related protein(Yap) and its phosphorylation in the downstream of Hippo signaling pathway were measured by Western blot. RESULTS: Compared with the male mice of the control group, the anal genital distances of the treatment group were significantly shortened((9. 2501±2. 5504) vs. (16. 1253±1. 3562) mm, P<0. 05), the quality of the penises was significantly less than((0. 0293±0. 0075) vs. (0. 4731±0. 004) g, P<0. 05), the length of the penises was shorter((5. 3875±0. 4524) vs. (12. 4688±1. 2290) mm, P<0. 05), and the diameters of the penises were also less than the control((1. 5513±0. 1158) vs. (2. 6013±0. 1469) mm, P<0. 05). All the genes in the penises of the control group were expressed. The Yap and Ar in the treatment group's penises were not expressed, the expression abundance of Mst1 and Lats1 was higher than that of the control(6. 6097±1. 3188 vs. 0. 3517±0. 1524, 5. 7071±2. 7210 vs. 0. 1235±0. 0658, P<0. 05), and the expression abundance of Taz was lower than that of the control(0. 3937±0. 1519 vs. 3. 2329±0. 4339, P<0. 05). The expression of Yap was decreased in the treatment group(0. 3348±0. 0639 vs. 0. 8023±0. 4275, P<0. 05), and the phosphorylation level of Yap was higher than that of the control group(3. 9940±0. 2177 vs. 0. 3128±0. 0867, P<0. 05). CONCLUSION: In the model of mice hypospadias induced by vinclozolin, the Ar was not expressed, the Hippo signaling pathway was activated and the phosphorylation of Yap was increased. This pathway may play an important role in the model.

Terpenoids from Euphorbia pekinensis.

Euphorpekone A (1) and euphorpekone B (2), two new diterpenoids, 3ß-hydroxy-25-methyloxylanosta-8,23-diene, a new triterpenoid (3), together with a known triterpenoid, 3ß,25-dihydroxylanosta-8,23-diene (4), were isolated from Euphorbia pekinensis Rupr. Their structures were elucidated on the basis of UV, IR, 1D ((1)H, (13)C, NOE) and 2D ((1)H-(1)H COSY, HSQC, HMBC) NMR, HR-ESI-MS, X-ray diffraction analysis, and CD method.

Determination of lithium ions by stripping voltammetry using single-crystal LiFePO4.

Determination of lithium ions is very important for extraction of lithium from salt lakes. Electrochemical sensor is an ideal choice, but it is not available so far. Here, a voltammetric sensor based on lithium iron phosphate (LiFePO4) was developed. Single-crystal LiFePO4 dominated by the (010) lattice plane was synthesized using hydrothermal method; it had good selectivity for lithium ions. Lithium ions were preferentially intercalated into LiFePO4 even if molar ratio of sodium ions, potassium ions, magnesium ions or calcium ions to lithium ions reached 10:1. The intercalation and deintercalation of interfering ions should be avoided because this reduced the selectivity of LiFePO4 for lithium ions. Lithium ion concentration of synthetic Uyuni Salt Lake solution was determined using the standard addition method. The measurement result was only 0.34 % higher than the theoretical value. The sensor provides a highly selective lithium ion analysis method at an extremely low cost, which was very promising to be widely used.

TT-10 may attenuate ibuprofen-induced ovarian injury in mice by activating COX2-PGE2 and inhibiting Hippo pathway.

Ibuprofen (IBU) is a non-steroidal anti-inflammatory drug that has been found in recent years to cause ovarian damage. The aim of this study is to explore the molecular mechanisms of IBU damage to the ovary and drugs to combat it. We established in vivo (IBU doses of 50, 100 and 200 mg/kg-day) and in vitro (IBU concentrations of 50, 100 and 200 µM in culture medium) models of ovarian damage in mice simulating clinical doses and found that IBU not only caused ovarian damage in mice in a dose-response relationship, but also decreased estradiol (E2) and prostaglandin E2 (PGE2) levels in serum/media with increasing IBU doses. In damaged ovaries, the cyclooxygenase 2 (COX2)-PGE2 pathway is inhibited, the Hippo pathway is activated, circPVT1 is decreased, and miR-149 is elevated. TT-10 is an activator of YES-associated protein (YAP)-transcriptional enhancer factor domain activity. Then, 100 µM IBU-induced ovarian damage model was selected for YAP activation (Hippo pathway inhibition) experiment, and TT-10 was found to interfere with IBU-induced ovarian damage and increase E2 level in the medium, and 10 µM of TT-10 had the best protective effect. TT-10 also inhibited the Hippo pathway, activated the COX2-PGE2 pathway, elevated circPVT1 expression, and decreased miR-149 expression in the ovary. It has been hypothesized that clinical doses of IBU damage mouse ovaries by inhibiting COX2-PGE2 and activating the Hippo pathway, whereas TT-10 protects the ovaries through the inverse regulation of these two pathways.

Short-chain chlorinated paraffins may induce thymic aging in mice by activating PERK-CHOP.

Humans indirectly consume approximately 0.02 mg/kg/day of short-chained chlorinated paraffins (SCCPs) through the environment; however, the thymic senescence/damage induced by SCCPs has not been assessed. In this study, 16 female mice (4-week-old) per group were orally administered 0, 0.01, 0.1, and 1 mg/kg/day of SCCPs for 21 days, and the phenotypes and levels of superoxide dismutase (SOD), malondialdehyde (MDA), Tß4, αß TCR, SA-ß-Gal, GRP78, PERK/CHOP, P53/P21, and CASPASE-1 of the thymus were assessed as indicators. Another group comprising 16 mice was killed at 4-week-old and these indicators were assessed. Thereafter, the thymuses cultured in vitro were exposed to 0, 14, 140, and 1400 µg/L SCCPs, respectively, and the above indicators were measured after 7-day. Based on the results, the oral administration of ≥0.01 mg/kg/day SCCPs to mice and ≥14 µg/L of SCCPs in medium caused thymic aging features, such as a decrease in the ratio of cortex to medulla, gradual blurring of the boundary between the cortex and medulla, dose-dependent oxidative stress (decreased SOD and increased MDA), and decreased levels of Tß4 and αß TCRs in the thymus. The oral administration of ≥1 mg/kg/day of SCCPs also impeded the growth and development of female mice and their thymuses. Exposure to the low levels of SCCPs activated PERK-CHOP in the mouse thymus, which modulated increases in SA-ß-Gal, IL-1ß, P53, and CASPASE-1 in vivo and in vitro. Overall, environmental levels and human blood concentrations (14.8-1400 µg/L) of SCCPs may induce mouse thymus senescence by activating PERK-CHOP in vivo and in vitro, respectively.

Accentuated Hippo pathway and elevated miR-132 and miR-195a lead to changes of uteri and ovaries in offspring mice following prenatal exposure to vinclozolin.

Vinclozolin (VCZ) has been identified as a broad-spectrum fungicide and an environmental endocrine disruptor. Also, the Hippo signaling pathway controls organ size by regulating cell proliferation and apoptosis, and moreover, overexpression of microRNA-132 (miR-132) and microRNA-195 (miR-195) inhibits cell proliferation and promotes apoptosis. So, in this study, the experimental mice were orally given 400 mg/kg/day VCZ (suspended in corn oil) at gestational day 12-18, while those of the control group were fed with corn oil of equal volume. Then unilateral ovaries and mid-uteri were isolated from 10 randomly-selected mice at the postnatal 1st week (7 days), 3rd week (20-21 days), and 7th week (48-49 days) respectively to observe gene levels, while 6 of the contralateral ovaries and uteri were subsequently examined for proteins respectively. Besides, 16 from both groups were determined with serum estradiol (E2) at week 7, of which 6 were randomized for histological observation. Here we found the levels of E2 reduced in VCZ-group at week 7, with fewer follicles and injured endometrium. Meanwhile, in VCZ mice of all ages, increased miR-132 and miR-195a, decreased G protein-coupled estrogen receptor (GPER), elevated phosphorylated large tumor suppressor (pLATS) and phosphorylated yes-associated protein (pYAP), and decreased yes-associated protein (YAP) were observed in their ovaries and uteri. These findings suggested ovarian and uterine dysplasia in the offspring induced by gestational VCZ-exposure were mainly attributed to higher miR-132 and miR-195a and accentuated Hippo-pathway.

TT-10 may elevate YAP and repair mouse uterine damage resulting from the inhibition effect of ibuprofen on COX2-PGE2 and YAP.

Ibuprofen (IBU) is an emerging environmental contaminant that, in high doses, can damage reproductive organs in humans and other mammals. Recently, its effects on the uterus have been investigated. It is known that the COX2-PGE2 pathway and Yes-associated protein (YAP) are involved in female reproductive organ development and form a COX2-PGE2-EP2-Gas-ß-catenin-YAP-COX2 positive feedback loop, in addition, TT-10, a pharmacological product, has been found to increase YAP. In this study, IBU was orally administrated to female mice for 7 d at doses of 0, 50, 100, and 200 mg/kg·bw/day (control, low, medium, and high doses, respectively). In addition, 0, 50, 100, and 200 µmol/L IBU was added in vitro to cultured uterine cells for 7 d at control, low, medium, and high doses, respectively; then, 0, 5, 10, and 20 µmol/L TT-10 were given to the in vitro uterine culture containing 100 µmol/L IBU to observe the effect of YAP activation. The results showed that medium and high doses of IBU inhibited the COX2-PGE2 pathway, decreasing YAP and increasing pYAP, leading to reduced circPVT1, elevated miR-149, and increased apoptosis, ultimately damaging the uterus. Conversely, 10 µmol/L TT-10 maximally enhanced YAP, which regulated COX2-PGE2 pathway activation, increased circPVT1, and decreased miR-149, and promoted cell proliferation, preventing uterine damage. This suggests that IBU may cause uterine damage by inhibiting the COX2-PGE2 pathway and YAP, and that appropriate doses of TT-10 may repair this damage by elevating YAP and stimulating COX2 via the feedback loop.

Two-Dimensional Materials Applied in Membranes of Redox Flow Battery.

Redox flow batteries (RFBs) are one of the most promising techniques to store and convert green and renewable energy, benefiting from their advantages of high safety, flexible design and long lifespan. Membranes with fast and selective ions transport are required for the advances of RFBs. Remarkably, two-dimensional (2D) materials with high mechanical and chemical stability, strict size exclusion and abundantly modifiable functional groups, have attracted extensive attentions in the applications of energy fields. Herein, the improvements and perspectives of 2D materials working for ionic transportation and sieving in RFBs membranes are presented. The characteristics of various materials and their advantages and disadvantages in the applications of RFBs membranes particularly are focused. This review is expected to provide a guidance for the design of membranes based on 2D materials for RFBs.

A Stable and Energy-Dense Polysulfide/Permanganate Flow Battery.

Redox flow batteries (RFBs) as promising technologies for energy storage have attracted burgeoning efforts and have achieved many advances in the past decades. However, for practical applications, the exploration of high-performance RFB systems is still of significance. In this work, inspired by the high solubility and low cost of both polysulfides and permanganates, the S/Mn RFBs with S42-/S22- and MnO4-/MnO42- as negative and positive redox pairs are demonstrated. Moreover, to solve the poor cycling performance caused by the sluggish kinetics of polysulfide-involved redox reactions and instability of the carbon felt (CF) electrode in the strong oxidative and corrosive catholyte, both the anode and cathode are designed to obtain high performance. Herein, the NiSx/Ni foam exhibiting electrocatalysis activity toward polysulfide ions is prepared and works as the anode while the graphene-modified carbon felt (G/CF) with high stability is fabricated and utilized as the cathode. Additionally, NaMnO4 with a high solubility limit (3.92 M) in the alkaline supporting electrolyte is preferred to KMnO4 as the redox-active molecule in the catholyte. The resulting S/Mn RFB cells show outstanding cell performance, such as high energy density (67.8 Wh L-1), long cycling lifetime with a temporal capacity fade of 0.025% h-1, and low chemical cost of electrolytes (17.31 $ kWh-1). Moreover, a three-cell stack shows good cycling stability over 100 cycles (226.8 h) with high performance, verifying the good scalability of the proposed S/Mn RFB system. Therefore, the present strategy provides a reliable candidate for stable, energy-dense, and cost-effective devices for future energy storage applications.