Plasticity in single-crystalline Mg3Bi2 thermoelectric material.

Most of the state-of-the-art thermoelectric materials are inorganic semiconductors. Owing to the directional covalent bonding, they usually show limited plasticity at room temperature1,2, for example, with a tensile strain of less than five per cent. Here we discover that single-crystalline Mg3Bi2 shows a room-temperature tensile strain of up to 100 per cent when the tension is applied along the (0001) plane (that is, the ab plane). Such a value is at least one order of magnitude higher than that of traditional thermoelectric materials and outperforms many metals that crystallize in a similar structure. Experimentally, slip bands and dislocations are identified in the deformed Mg3Bi2, indicating the gliding of dislocations as the microscopic mechanism of plastic deformation. Analysis of chemical bonding reveals multiple planes with low slipping barrier energy, suggesting the existence of several slip systems in Mg3Bi2. In addition, continuous dynamic bonding during the slipping process prevents the cleavage of the atomic plane, thus sustaining a large plastic deformation. Importantly, the tellurium-doped single-crystalline Mg3Bi2 shows a power factor of about 55 microwatts per centimetre per kelvin squared and a figure of merit of about 0.65 at room temperature along the ab plane, which outperforms the existing ductile thermoelectric materials3,4.

Scale Effect of Surface Asperities on Stick-Slip Behavior of Zinc-Coated Steel.

Stick-slip behavior between friction pairs causes severe vibration problems such as abrasion and noise pollution, leading to material loss and deterioration in human health. This phenomenon is extremely complex because the surfaces of friction pairs have various asperities with different sizes. Therefore, it is of importance to understand the scale effect of asperities on the stick-slip behavior. Here, we selected four kinds of zinc-coated steels with multiscale surface asperities as a presentative example to reveal what types of asperities play the key role in affecting the stick-slip behavior. It is discovered that the stick-slip behavior is dominated by the density of small-scale asperities rather than large-scale asperities. High-density small-scale asperity increases the potential energy between asperities of the friction pairs, which leads to stick-slip behavior. It is suggested that decreasing the density of small-scale asperity on the surface significantly suppresses the stick-slip behavior. The present study reveals the scale effect of surface asperities on the stick-slip behavior and thus could offer a pathway to tailoring the surface topography of a wide range of materials for suppressing the stick-slip behavior.

Circadian clock regulates granulosa cell autophagy through NR1D1-mediated inhibition of ATG5.

Autophagy of granulosa cells (GCs) is involved in follicular atresia, which occurs repeatedly during the ovarian development cycle. Several circadian clock genes are rhythmically expressed in both rodent ovarian tissues and GCs. Nuclear receptor subfamily 1 group D member 1 (NR1D1), an important component of the circadian clock system, is involved in the autophagy process through the regulation of autophagy-related genes. However, there are no reports illustrating the role of the circadian clock system in mouse GC autophagy. In the present study, we found that core circadian clock genes (Bmal1, Per2, Nr1d1, and Dbp) and an autophagy-related gene (Atg5) exhibited rhythmic expression patterns across 24 h in mouse ovaries and primary GCs. Treatment with SR9009, an agonist of NR1D1, significantly reduced the expression of Bmal1, Per2, and Dbp in mouse GCs. ATG5 expression was significantly attenuated by SR9009 treatment in mouse GCs. Conversely, Nr1d1 knockdown increased ATG5 expression in mouse GCs. Decreased NR1D1 expression at both the mRNA and protein levels was detected in the ovaries of Bmal1-/- mice, along with elevated expression of ATG5. Dual-luciferase reporter assay and electrophoretic mobility shift assay showed that NR1D1 inhibited Atg5 transcription by binding to two putative retinoic acid-related orphan receptor response elements within the promoter. In addition, rapamycin-induced autophagy and ATG5 expression were partially reversed by SR9009 treatment in mouse GCs. Taken together, our current data demonstrated that the circadian clock regulates GC autophagy through NR1D1-mediated inhibition of ATG5 expression, and thus, plays a role in maintaining autophagy homeostasis in GCs.

Two Novel Three-Dimensional Tetraphenylethylene-Based Rare Earth MOFs with Ultra-High Proton Conductivity and Performance Stability.

Invited for the cover of this issue are the groups of Lin Du and Qi-Hua Zhao at Yunnan University. The image depicts astronauts as protons moving along the hydrogen-bond network in the channel of Eu-ETTB/Gd-ETTB. Read the full text of the article at 10.1002/chem.202202154.

Two Novel Three-Dimensional Tetraphenylethylene-Based Rare Earth MOFs with Ultra-High Proton Conductivity and Performance Stability.

In this work, the two example rare earth-based metal-organic frameworks (LaIII -based MOFs), Eu-ETTB and Gd-ETTB, were obtained by self-assembly. Both materials showed extremely high proton conductivity, with the proton conductivity of Eu-ETTB being 1.53×10-2  S cm-1 at 98 % relative humidity (RH) and 85 °C and that of Gd-ETTB being 2.63×10-2  S cm-1 at 98 % RH and 75 °C. This was almost the best performance observed for three-dimensional porous MOFs without post-synthetic modification and was based on milder conditions than for most materials. Furthermore, cycle test experiments and continuous work tests showed that both materials had excellent performance both in terms of stability and durability. Water vapor adsorption experiments showed that a large number of water molecules are adsorbed the hydrogen-bond network's being rebuilt by the adsorbed water molecules in the pore channel and thus optimizing the channels for proton transfer explained the MOF's high performance.

Effect of Wear-Induced Surface Deformation on Stick-Slip Friction of Galvanized Automotive Steels.

This study examined the influence of worn surfaces on the stick-slip friction of galvanized automotive steel and revealed the intrinsic role of surface topography parameters in the stick-slip friction with wear. The results show that the surface deformation induced by wear significantly affects the stick-slip friction. The stick-slip friction can be suppressed by increasing the vertical area of the surface deformation because of reductions in the difference between the static and kinetic friction coefficients. The friction behavior changes from stick-slip friction to smooth sliding when the skewness exceeds a critical value, thus suggesting that this parameter can be used as an effective surface topography parameter to describe the stick-slip friction of galvanized automotive steel with worn surfaces. The findings can help improve the understanding of the mechanism of the stick-slip friction of materials with worn surfaces and provide an approach to suppress the noise and vibration caused by the stick-slip friction of galvanized automotive steel.

Anion-Controlled Assembly of a Silver-Responsive Bifunctional Coordination Polymer with Detection and Large Adsorption Capacity.

The recognition and adsorption of silver ions (Ag+) from industrial wastewater are necessary but still challenging. Herein, we constructed four Zn(II)-based coordination polymers (CPs), namely, [Zn(btap)2(NO3)2]n (1), [Zn(btap)(SO4)(H2O)3]n (2), {[Zn(btap)2(H2O)2]·(ClO4)2}n (3), and [Zn(btap)Cl2]n (4), by using 3,5-bis(triazol-1-yl)pyridine (btap) with different anionic Zn(II) salts. The crystal structures of 1-4, varying from one-dimensional beaded (1) and zigzag chain (2) to two-dimensional sql (3) and bex (4) typologies, were regulated by the coordination modes of btap and the counter-anions. The water stability, pH stability, thermostability, and luminescent properties of the CPs were investigated. The luminescence performances in a series of cations and anions were also explored. Considering the high density of chloride groups in the structure, 4 showed luminescence sensing for Ag+ [KSV = 9188.45 M-1 and a limit of detection (LOD) of 4.9 µM], as well as an excellent ability for Ag+ adsorption in aqueous solution (maximum adsorption capacity, 653.3 mg/g). Additionally, anti-interference experiments revealed that 4 had excellent recognition and adsorption capacities for Ag+ even when multiple ions coexisted. Moreover, XRD, EDS, and XPS analyses confirmed that the coordination of Ag+ with chloride groups in 4 resulted in excellent adsorption capacity and prevented ligand-to-ligand electron transfer, showing excellent detection ability. Suitable coordination sites were introduced to interact strongly with Ag+, along with detection and large adsorption capacity. Our strategy can effectively design and develop multifunctional CP-based materials, which are applicable in removal processes and environmental protection, by regulating anions in the self-assembly and introducing CP functional groups.

Circadian clock gene BMAL1 controls testosterone production by regulating steroidogenesis-related gene transcription in goat Leydig cells.

Testosterone is produced by Leydig cells (LCs) and undergoes diurnal changes in serum levels in rats, mice, and humans, but little is known in goats. The present study revealed that goat serum testosterone levels displayed diurnal rhythmic changes (peak time at ZT11.2). Immunohistochemical staining showed that BMAL1, a circadian clock protein, is highly expressed in goat LCs. ELISA revealed that both hCG (0-5 IU/ml) and 22R-OH-cholesterol (0-30 µM) addition stimulated testosterone synthesis in primary goat LCs in a dose-dependent manner. Treating goat LCs with hCG (5 IU/ml) significantly increased intracellular cAMP levels. Additionally, real-time quantitative polymerase chain reaction (PCR) analysis revealed that the circadian clock (BMAL1, PER1, PER2, DBP, and NR1D1) and steroidogenesis-related genes (SF1, NUR77, StAR, HSD3B2, CYP17A1, CYP11A1, and HSD17B3) showed rhythmic expression patterns in goat LCs following dexamethasone synchronization. Several Bmal1-Luc circadian oscillations were clearly observed in dexamethasone-treated goat LCs transfected with the pLV6-Bmal1-Luc plasmid. BMAL1 knockdown significantly downregulated mRNA levels of PER2, NR1D1, DBP, StAR, HSD3B2, SF1, NUR77, and GATA4, and dramatically decreased StAR and HSD3B2 protein levels and testosterone production. In contrast, BMAL1 overexpression significantly increased the mRNA and protein expression levels of StAR and HSD17B3 and enhanced testosterone production. Reporter assays revealed that goat BMAL1, or in combination with mouse CLOCK, activated goat HSD17B3 transcription in vitro. These data indicate that BMAL1 contributes to testosterone production by regulating transcription of steroidogenesis-related genes in goat LCs, providing a basis for further exploring the underlying mechanism by which the circadian clock regulates ruminant reproductive capability.

Bmal1 promotes prostaglandin E2 synthesis by upregulating Ptgs2 transcription in response to increasing estradiol levels in day 4 pregnant mice.

Prostaglandin G/H synthase 2 (PTGS2) is a rate-limiting enzyme in prostaglandin synthesis. The present study assessed the role of the uterine circadian clock on Ptgs2 transcription in response to steroid hormones during early pregnancy. We demonstrated that the core clock genes (Bmal1, Per2, Nr1d1, and Dbp), Vegf, and Ptgs2, and their encoded proteins, have rhythmic expression in the mouse uterus from days 3.5 to 4.5 (D3.5-4.5) of pregnancy. Progesterone (P4) treatment of cultured uterus endometrial stromal cells (UESCs) isolated from mPer2Luciferase reporter gene knock-in mice on D4 induced a phase shift in PER2::LUCIFERASE oscillations. This P4-induced phase shift of PER2::LUCIFERASE oscillations was significantly attenuated by the P4 antagonist RU486. Additionally, the amplitude of PER2::LUCIFERASE oscillations was increased by estradiol (E2) treatment in the presence of P4. Consistently, the mRNA levels of clock genes (Bmal1 and Per2), Vegf, and Ptgs2 were markedly increased by E2 treatment of UESCs in the presence of P4. Treatment with E2 also promoted prostaglandin E2 (PGE2) synthesis by UESCs. Depletion of Bmal1 in UESCs by small-interfering RNA (siRNA) decreased the transcript levels of clock genes (Nr1d1 and Dbp), Vegf, and Ptgs2 compared with nonsilencing siRNA treatment. Bmal1 knockdown also inhibited PGE2 synthesis. Moreover, the mRNA expression levels of clock genes (Nr1d1 and Dbp), Vegf, and Ptgs2, and their respective proteins were significantly decreased in the uterus of Bmal1-/- mice. Thus, these data suggest that Bmal1 in mice promotes PGE2 synthesis by upregulating Ptgs2 in response to increases in E2 on D4 of pregnancy.NEW & NOTEWORTHY Rhythmic expression of Bmal1 and Ptgs2 was observed in the uterus isolated from D3.5-4.5 of pregnant mice. E2 increased the expression of Bmal1 and Ptg2 in UESCs isolated from mice on D4. The expression of Ptgs2 was significantly decreased in Bmal1-siRNA treated UESCs. Bmal1 knockdown also inhibited PGE2 synthesis. Thus, these data suggest that Bmal1 in mice promotes PGE2 synthesis by upregulating Ptgs2 in response to increases in E2 on D4 of pregnancy.

Multiple Strategies to Fabricate a Highly Stable 2D CuIICuI-Organic Framework with High Proton Conductivity.

Using multifunctional organic ligands with multiple acidic groups (carboxylate and sulfonate groups) to synthesize metal-organic frameworks (MOFs) bearing effective H-bond networks is a promising strategy to obtain highly proton conductive materials. In this work, a highly stable two-dimensional MOF, [CuII5CuI2(µ3-OH)4(H2O)6(L)2(H2L)2]·3H2O (denoted as YCu161; H3L = 6-sulfonaphthalene-1,4-dicarboxylic acid) containing mixed-valence [CuII5CuI2(µ3-OH)4]8+ subunits, was successfully prepared. It exhibited excellent stability and temperature- and humidity-dependent proton conduction properties. Its optimal proton conductivity reached 1.84 × 10-3 S cm-1 at 90 °C and 98% relative humidity. On the basis of a crystal structure analysis, water vapor adsorption test results, and activation energy calculations, we deduced the proton conduction pathway and mechanism. Apparently, uncoordinated sulfonic and carboxyl groups and a network of abundant H-bonds inside the framework were responsible for the efficient proton transfer. Therefore, the strategy of selecting suitable bifunctional ligands to construct two-dimensional Cu-cluster-based MOFs with excellent proton conductivity is feasible.

Zearalenone perturbs the circadian clock and inhibits testosterone synthesis in mouse Leydig cells.

Zearalenone (ZEA), a mycotoxin, is known to impair reproductive capability by disrupting the synthesis and secretion of testosterone by Leydig cells (LCs), although the mechanism is unknown. Robust rhythmicity of circadian clock and steroidogenic genes were identified in LCs. The aim of this study was to examine whether ZEA significantly attenuated the transcription of core clock genes (Bmal1, Dbp, Per2, and Nr1d1) as well as steroidogenic genes (StAR, Hsd3b2, and Cyp11a1) in mouse testis Leydig cell line (TM3). Western blotting confirmed declines in BMAL1, NR1D1, and StAR protein levels. ZEA also suppressed secreted testosterone levels. In primary LCs, isolated from PER2::LUCIFERASE reporter gene knock in mice, ZEA diminished the amplitude of PER2::LUC expression, and induced a phase shift and period extension. In primary LCs, ZEA also suppressed the expression levels of core clock and steroidogenic genes, reduced protein levels of BMAL1, and decreased testosterone secretion. In vivo expression of core clock and steroidogenic genes were reduced in testes of mice exposed to ZEA for 1 week leading to decreased serum testosterone levels. In summary, data suggest that ZEA may impair testosterone synthesis through attenuation of the circadian clock in LCs culminating in reproductive dysfunction in male mammals .

Focused Ion Beam-Induced Displacive Phase Transformation From Austenite to Martensite during Fabrication of Quenched and Partitioned Steel Micro-Pillar.

We report evidence of a displacive phase transformation from retained austenite to martensite during preparation of quenched and partitioned steel micro-pillars by using a focused ion beam (FIB) technique. The BCC phase produced by the FIB damage was identified as martensite. The invariant-plane strain surface relief associated with the martensitic transformation was observed in the retained austenite phase immediately after a FIB scan of the surface with the Ga+ ion beam. Use of a low acceleration voltage appears to lower the probability of the phase transformation, while a decrease of the acceleration voltage will result in an increase of the total milling time required to prepare a micro-pillar. This report addresses challenges related to the preparation of austenite micro-pillars by a conventional FIB technique.

Inhibitory role of REV-ERBα in the expression of bone morphogenetic protein gene family in rat uterus endometrium stromal cells.

Uterus circadian rhythms have been implicated in the gestation processes of mammals through entraining of the clock proteins to numerous downstream genes. Bone morphogenetic proteins (BMPs), having clock-controlled regulatory sites in their gene promoters, are expressed in the uterus during decidualization, but the regulation of the Bmp gene expression is poorly understood. The present study was designed to dissect the physiological roles of the uterus oscillators in the Bmp expression using the uterus endometrial stromal cells (UESCs) isolated from Per2-dLuc transgenic rats on day 4.5 of gestation. The in vitro decidualization of UESCs was induced by medroxyprogesterone acetate and 2-O-dibutyryl cAMP. A significant decline of Per2-dLuc bioluminescence activity was induced in decidual cells, and concomitantly, the expression of canonical clock genes was downregulated. Conversely, the expression of the core Bmp genes Bmp2, Bmp4, Bmp6, and Bmp7 was upregulated. In UESCs transfected with Bmal1-specific siRNA, in which Rev-erbα expression was downregulated, Bmp genes, such as Bmp2, Bmp4, and Bmp6 were upregulated. However, Bmp1, Bmp7, and Bmp8a were not significantly affected by Bmal1 silencing. The expression of all Bmp genes was enhanced after treatment with the REV-ERBα antagonist (SR8278), although their rhythmic profiles were differed from each other. The binding of REV-ERBα to the proximal regions of the Bmp2 and Bmp4 promoters was revealed by chromatin immunoprecipitation-PCR analysis. Collectively, these results indicate that the Bmp genes are upregulated by the attenuation of the cellular circadian clock; in particular, its core component REV-ERBα functions as a transcriptional silencer in the Bmp gene family.

Removal of Rev-erbα inhibition contributes to the prostaglandin G/H synthase 2 expression in rat endometrial stromal cells.

The rhythmic expression of clock genes in the uterus is attenuated during decidualization. This study focused on Ptgs2, which is essential for decidualization, as a putative clock-controlled gene, and aimed to reveal the functions of clock genes in relation to Ptgs2 during decidualization. We compared the transcript levels of clock genes in the rat uterus on days 4.5 (D4.5) and 6.5 of pregnancy. The transcript levels of clock genes (Per2, Bmal1, Rorα, and Rev-erbα) had decreased at implantation sites on day 6.5 (D6.5e) compared with those on D4.5, whereas Ptgs2 transcripts had increased on D6.5e. Similar observations of Rev-erbα and Ptgs2 were also obtained in the endometrium on D6.5e by immunohistochemistry. In the decidual cells induced by medroxyprogesterone and 2-O-dibutyryl-cAMP, the rhythmic expression levels of clock genes were attenuated, whereas Ptgs2 transcription was induced. These results indicate that decidualization causes the attenuation of clock genes and the induction of Ptgs2. Furthermore, in the experiment of Bmal1 siRNA, the rhythmic expression of clock genes and Ptgs2 was attenuated by the siRNA. Transcript levels of Ptgs2 and prostaglandin (PG)E2 production were increased by treatment with the Rev-erbα antagonist, suggesting the contribution of the nuclear receptor Rev-erbα to Ptgs2 expression. Moreover, Rev-erbα knockdown enhanced the induction of Ptgs2 transcription and PGE2 production by forskolin. Chromatin immunoprecipitation-PCR analysis revealed that Rev-erbα could directly bind to a proximal RORE site of Ptgs2. Collectively, this study demonstrates that the attenuation of the circadian clock, especially its core component Rev-erbα, contributes to the induction of Ptgs2 during decidualization.

Effect of dipeptidyl peptidase-4 inhibitors on tumor necrosis factor alpha levels in patients with type 2 diabetes mellitus.

AIMS: Dipeptidyl peptidase-4 inhibitors (DPP-4i) served as oral antidiabetic agents for treatment of type 2 diabetes mellitus (T2DM). Although an action on glucose homeostasis was identified, no well-rounded illustration had been established on the changes of tumor necrosis factor alpha (TNF-alpha) levels during DPP-4i treatment. This study aimed to explore the anti-inflammatory effect of DPP-4i on TNF-alpha in patients with T2DM. METHODS: PubMed, Embase and Cochrane Library were systematically searched from inception to May 31, 2024. Randomized controlled trials exploring the impact of DPP-4i on TNF-alpha levels were identified. Risk of bias was assessed according to the Cochrane criteria. A fixed or random-effects model was selected to pool estimate on whether the heterogeneity was present. Subgroup analysis were performed to explore the potential factors that influenced heterogeneity. Related meta-analysis was conducted with the software of Revman 5.3 and STATA 12.0. RESULTS: Eleven trials involving 884 participants with T2DM were included. Pooled estimates suggested that DPP-4i did not significantly modulate TNF-alpha levels (WMD, - 0.70, 95% CI - 1.94 to 0.53, P = 0.26) in T2DM. DPP-4i produced a significant effect on TNF-alpha (WMD, - 4.50 pg/mL, 95% CI - 4.68 to - 4.32, P < 0.00001) when compared to placebo, and a comparable effect was demonstrated on TNF-alpha (WMD, 0.10 pg/mL, 95% CI - 0.11 to 0.30, P = 0.35) in comparison with active agents. Estimate was stable according to the sensitivity test. Subgroup analysis revealed that heterogeneity might not correlate with baseline glycated hemoglobin (HbA1c), age or treatment duration. CONCLUSIONS: A significant effect of DPP-4i on TNF-alpha levels was present in T2DM when compared to placebo. Administration of DPP-4i produced no significant effect on TNF-alpha in comparison with active comparators. Further studies with large samples should be performed to illustrate the impact of DPP-4i on TNF-alpha levels in T2DM. Trial registration International Prospective Register for Systematic Review (PROSPERO) number: CRD42020185479.

Downregulation of core clock gene Bmal1 attenuates expression of progesterone and prostaglandin biosynthesis-related genes in rat luteinizing granulosa cells.

Ovarian circadian oscillators have been implicated in the reproductive processes of mammals. However, there are few reports regarding the detection of ovarian clock-controlled genes (CCGs). The present study was designed to unravel the mechanisms through which CCG ovarian circadian oscillators regulate fertility, primarily using quantitative RT-PCR and RNA interference against Bmal1 in rat granulosa cells. Mature granulosa cells were prepared from mouse Per2-destabilized luciferase (dLuc) reporter gene transgenic rats. A real-time monitoring system of Per2 promoter activity was employed to detect Per2-dLuc oscillations. The cells exposed to luteinizing hormone (LH) displayed clear Per2-dLuc oscillations and a rhythmic expression of clock genes (Bmal1, Per1, Per2, Rev-erbα, and Dbp). Meanwhile, the examined ovarian genes (Star, Cyp19a1, Cyp11a1, Ptgs2, Lhcgr, and p53) showed rhythmic transcript profiles except for Hsd3b2, indicating that these rhythmic expression genes may be CCGs. Notably, Bmal1 small interfering (si)RNA treatment significantly decreased both the amplitude of Per2-dLuc oscillations and Bmal1 mRNA levels compared with nonsilencing RNA treatment in luteinizing granulosa cells. Depletion of Bmal1 by siRNA decreased the transcript levels of clock genes (Per1, Per2, Rev-erbα, and Dbp) and examined ovarian genes (Star, Cyp19a1, Cyp11a1, Ptgs2, Hsd3b2, and Lhcgr). Accordingly, knockdown of Bmal1 also inhibited the synthesis of progesterone and prostaglandin E2, which are associated with crucial reproductive processes. Collectively, these data suggest that ovarian circadian oscillators regulate the synthesis of steroid hormones and prostaglandins through ovarian-specific CCGs in response to LH stimuli. The present study provides new insights into the physiologic significance of Bmal1 related to fertility in ovarian circadian oscillators.

FSH induces the development of circadian clockwork in rat granulosa cells via a gap junction protein Cx43-dependent pathway.

The present study was designed to assess the relationship between gap junctions and the maturation of a clock system in rat granulosa cells stimulated by follicle-stimulating hormone (FSH). Immature and mature granulosa cells were prepared by puncturing the ovaries of diethylstilbestrol- and equine chorionic gonadotropin (eCG)-treated mouse Period2 (Per2)-dLuc reporter gene transgenic rats, respectively. Mature granulosa cells exposed to dexamethasone (DXM) synchronization displayed several Per2-dLuc oscillations and a rhythmic expression of clock genes. Intriguingly, we observed clear evidence that the FSH stimulation significantly increased the amplitude of Per2 oscillations in the granulosa cells, which was confirmed by the elevation of the Per2 and Rev-erbα (Nr1d1) mRNA levels. FSH also induced a major phase-advance shift of Per2 oscillations. The mature granulosa cells cultured for 2 days with FSH expressed higher mRNA levels of Per2, Rev-erbα, Bmal1 (Arnt1), Lhcgr, and connexin (Cx) 43 (Gja1) compared with the immature granulosa cells. Consistently, our immunofluorescence results revealed abundant Cx43 protein in antral follicles stimulated with eCG and weak or no fluorescence signal of Cx43 in primary and preantral follicles. Similar results were confirmed by Western blotting analysis. Two gap junction blockers, lindane and carbenoxolone (CBX), significantly decreased the amplitude of Per2 oscillations, which further adhered significant decreases in Per2 and Rev-erbα transcript levels. In addition, both lindane and CBX induced a clear phase-delay shift of Per2 oscillations. These findings suggest that FSH induces the development of the clock system by increasing the expression of Cx43.

Photo- and Thermal-Induced Ion Migration and Phase Separation in Mn-Doped Two-Dimensional PEA2PbX4 Perovskite.

Ion migration and phase separation in perovskite materials have negatively affected the solid-state lighting and display. Studying photo- and thermal-induced degradation is considered as a promising approach to understanding the luminescence mechanism and promoting practical applications. Herein, the Mn-doped two-dimensional PEA2PbX4 (X = Cl, Br, I) microcrystals with changing halogen composition were synthesized by an acid-assisted post-processing strategy. Then, photo- and thermal-induced degradation was studied by using steady-state and time-resolved photoluminescence (PL) spectroscopy. The band edge exciton PL peak of Mn-doped 2D PEA2PbX4 microcrystals was adjusted from 397 to 500 nm. The reduced Mn PL lifetime (1.37 to 0.21 ms) was monitored under ion exchange from Cl to Br to I. The degradation mechanism could be divided into two cases: (i) The halide ion migration in Mn-doped 2D perovskite under continuous illumination was revealed, suggesting that the migration of Cl ions was more accessible than that of Br and I. (ii) The PL redshift and lifetime reduction were observed after annealing at 420 K, which means that thermally induced aggregation of Mn ions resulted in the formation of Mn2+-Mn2+ dimers. In addition, the experimental results indicated that the induced B-site phase separation at high temperature annealing made the mixed perovskite phase of Pb and Mn ultimately transform into pure PEA2PbBr4 and PEA2MnBr4.

Autophagy activation attenuates the circadian clock oscillators in U2OS cells via the ATG5 pathway.

The circadian clock and autophagy are essential biological mechanisms involved in regulating many physiological processes. Accumulating evidence has revealed that autophagic activity is regulated by the circadian clock system. However, whether autophagy regulates the circadian clock system remains unclear. In this study, rapamycin and AICAR, two classical activators of autophagy, were used to create autophagy activation models in BMAL1-dLuc U2OS cell line. The results showed that the mRNA expression of MAP1LC3B and ATG5 were significantly upregulated after autophagy activation, whereas the mRNA expression of circadian clock genes (BMAL1, PER2, REV-ERBα, and DBP) were significantly decreased. Consistent with these data, the relative ratio of LC3-II/LC3-I and the protein level of ATG5 were increased after rapamycin or AICAR treatment. In contrast, BMAL1 and REV-ERBα levels were decreased. Notably, the mRNA expression of circadian clock genes (BMAL1, PER2, REV-ERBα, and DBP) and autophagy-related genes (MAP1LC3B and ATG5) showed rhythmic expression patterns in both untreated and rapamycin/AICAR-treated U2OS cells. Moreover, the autophagy inhibitor 3-methyladenine partially reversed the inhibitory effects of autophagy on circadian clock genes expression and BMAL1-Luc oscillations. Another critical finding was that ATG5 knockout alleviates the inhibitory effect of rapamycin-mediated autophagy activation on the circadian clock oscillators in U2OS cells. Collectively, our data indicate that autophagy activation attenuates the circadian clock oscillators in U2OS cells via the ATG5 pathway.

Rev-erbα regulates circadian rhythms and StAR expression in rat granulosa cells as identified by the agonist GSK4112.

The Rev-erbα gene is regarded as a circadian clock gene and clock-regulated gene which regulates the circadian transcriptional/translational loop in a subtle way. Here, we first detected the circadian oscillation in mature granulosa cells from antral follicles using a real-time monitoring system of Per2 promoter activity with the addition of FSH. Then we used GSK4112, an agonist ligand of Rev-erbα, to investigate the function of Rev-erbα. GSK4112 treatment significantly reduced the Per2-dLuc amplitude and induced the Per2 oscillation phase advance shift. GSK4112 significantly inhibited Bmal1 mRNA expression, whereas it did clearly stimulate expression of StAR mRNA in a dose-dependent manner. Our data are the first to show the Rev-erbα function in the steroid biosynthesis of rat granulosa cells, and to suggest that Rev-erbα may coordinate circadian rhythm and metabolism in rat ovaries.