Intrauterine hyperglycaemia during late gestation caused mitochondrial dysfunction in skeletal muscle of male offspring through CREB/PGC1A signaling.

BACKGROUND: Maternal diabetes mellitus can influence the development of offspring. Gestational diabetes mellitus (GDM) creates a short-term intrauterine hyperglycaemic environment in offspring, leading to glucose intolerance in later life, but the long-term effects and specific mechanism involved in skeletal muscle dysfunction in offspring remain to be clarified. METHODS: Pregnant mice were divided into two groups: The GDM group was intraperitoneally injected with 100 mg/kg streptozotocin on gestational days (GDs) 6.5 and 12.5, while the control (CTR) group was treated with vehicle buffer. Only pregnant mice whose random blood glucose level was higher than 16.8 mmol/L beginning on GD13.5 were regarded as the GDM group. The growth of the offspring was monitored, and the glucose tolerance test was performed at different time points. Body composition analysis and immunohistochemical methods were used to evaluate the development of lean mass at 8 weeks. The exercise capacity and grip strength of the male mouse offspring were assessed at the same period. Transmission electron microscopy was used to observe the morphology inside skeletal muscle at 8 weeks and as a foetus. The genes and proteins associated with mitochondrial biogenesis and oxidative metabolism were investigated. We also coanalyzed RNA sequencing and proteomics data to explore the underlying mechanism. Chromatin immunoprecipitation and bisulfite-converted DNA methylation detection were performed to evaluate this phenomenon. RESULTS: Short-term intrauterine hyperglycaemia inhibited the growth and reduced the lean mass of male offspring, leading to decreased endurance exercise capacity. The myofiber composition of the tibialis anterior muscle of GDM male offspring became more glycolytic and less oxidative. The morphology and function of mitochondria in the skeletal muscle of GDM male offspring were destroyed, and coanalysis of RNA sequencing and proteomics of foetal skeletal muscle showed that mitochondrial elements and lipid oxidation were consistently impaired. In vivo and in vitro myoblast experiments also demonstrated that high glucose concentrations impeded mitochondrial organisation and function. Importantly, the transcription of genes associated with mitochondrial biogenesis and oxidative metabolism decreased at 8 weeks and during the foetal period. We predicted Ppargc1α as a key upstream regulator with the help of IPA software. The proteins and mRNA levels of Ppargc1α in the skeletal muscle of GDM male offspring were decreased as a foetus (CTR vs. GDM, 1.004 vs. 0.665, p = 0.002), at 6 weeks (1.018 vs. 0.511, p = 0.023) and 8 weeks (1.006 vs. 0.596, p = 0.018). In addition, CREB phosphorylation was inhibited in GDM group, with fewer activated pCREB proteins binding to the CRE element of Ppargc1α (1.042 vs. 0.681, p = 0.037), Pck1 (1.091 vs. 0.432, p = 0.014) and G6pc (1.118 vs. 0.472, p = 0.027), resulting in their decreased transcription. Interestingly, we found that sarcopenia and mitochondrial dysfunction could even be inherited by the next generation. CONCLUSIONS: Short-term intrauterine hyperglycaemia significantly reduced lean mass in male offspring at 8 weeks, resulting in decreased exercise endurance and metabolic disorders. Disrupted organisation and function of the mitochondria in skeletal muscle were also observed among them. Foetal exposure to hyperglycaemia decreased the ratio of phosphorylated CREB and reduced the transcription of Ppargc1α, which inhibited the transcription of downstream genes involving in mitochondrial biogenesis and oxidative metabolism. Abnormal mitochondria, which might be transmitted through aberrant gametes, were also observed in the F2 generation.

Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes.

BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. CONCLUSION: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.

Glymphatic abnormality in systemic lupus erythematosus detected by diffusion tensor image analysis along the perivascular space.

OBJECTIVES: This study aimed to evaluate the activity of the glymphatic system in systemic lupus erythematosus (SLE) by a diffusion-based method termed "Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS)", and examined its correlations with morphological changes in the brain. METHODS: In this cross-sectional study, forty-five female patients with SLE and thirty healthy controls (HCs) were included. Voxel-based and surface-based morphometric analyses were performed to examine T1 weighted images, and diffusion tensor images were acquired to determine diffusivity along the x-, y-, and z-axes in the plane of the lateral ventricle body. The ALPS-index was calculated. The differences in values between SLE patients and HC group were compared using the independent samples t test or Mann-Whitney U test. For the correlations between the ALPS-index and brain morphological parameters, partial correlation analysis and Pearson's correlation analysis were conducted. RESULTS: SLE patients showed lower values for the ALPS-index in left (1.543 ± 0.141 vs 1.713 ± 0.175, p < 0.001), right (1.428 ± 0.142 vs 1.556 ± 0.139, p < 0.001) and whole (1.486 ± 0.121 vs 1.635 ± 0.139, p < 0.001) brain compared with the HC group. The reduced ALPS-index showed significant positive correlations with gray matter loss. CONCLUSION: The non-invasive ALPS-index could serve as a sensitive and effective neuroimaging biomarker for individually quantifying glymphatic activity in patients with SLE. Glymphatic system abnormality may be involved in the pathophysiologic mechanism underlying central nervous system damage in SLE patients.

Microstructural changes of the white matter in systemic lupus erythematosus patients without neuropsychiatric symptoms: a multi-shell diffusion imaging study.

BACKGROUND: Diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) provide more comprehensive and informative perspective on microstructural alterations of cerebral white matter (WM) than single-shell diffusion tensor imaging (DTI), especially in the detection of crossing fiber. However, studies on systemic lupus erythematosus patients without neuropsychiatric symptoms (non-NPSLE patients) using multi-shell diffusion imaging remain scarce. METHODS: Totally 49 non-NPSLE patients and 41 age-, sex-, and education-matched healthy controls underwent multi-shell diffusion magnetic resonance imaging. Totally 10 diffusion metrics based on DKI (fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, mean kurtosis, axial kurtosis and radial kurtosis) and NODDI (neurite density index, orientation dispersion index and volume fraction of the isotropic diffusion compartment) were evaluated. Tract-based spatial statistics (TBSS) and atlas-based region-of-interest (ROI) analyses were performed to determine group differences in brain WM microstructure. The associations of multi-shell diffusion metrics with clinical indicators were determined for further investigation. RESULTS: TBSS analysis revealed reduced FA, AD and RK and increased ODI in the WM of non-NPSLE patients (P < 0.05, family-wise error corrected), and ODI showed the best discriminative ability. Atlas-based ROI analysis found increased ODI values in anterior thalamic radiation (ATR), inferior frontal-occipital fasciculus (IFOF), forceps major (F_major), forceps minor (F_minor) and uncinate fasciculus (UF) in non-NPSLE patients, and the right ATR showed the best discriminative ability. ODI in the F_major was positively correlated to C3. CONCLUSION: This study suggested that DKI and NODDI metrics can complementarily detect WM abnormalities in non-NPSLE patients and revealed ODI as a more sensitive and specific biomarker than DKI, guiding further understanding of the pathophysiological mechanism of normal-appearing WM injury in SLE.

Systemic lupus erythematosus-related brain abnormalities in the default mode network and the limbic system: A resting-state fMRI meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an immune-mediated and multi-systemic disease which may affect the nervous system, causing neuropsychiatric SLE (NPSLE). Recent neuroimaging studies have examined brain functional alterations in SLE. However, discrepant findings were reported. This meta-analysis aims to identify consistent resting-state functional abnormalities in SLE. METHODS: PubMed and Web of Science were searched to identify candidate resting-state functional MRI studies assessing SLE. A voxel-based meta-analysis was performed using the anisotropic effect-size version of the seed-based d mapping (AES-SDM). The abnormal intrinsic functional patterns extracted from SDM were mapped onto the brain functional network atlas to determine brain abnormalities at a network level. RESULTS: Twelve studies evaluating fifteen datasets were included in this meta-analysis, comprising 572 SLE patients and 436 healthy controls (HCs). Compared with HCs, SLE patients showed increased brain activity in the bilateral hippocampus and right superior temporal gyrus, and decreased brain activity in the left superior frontal gyrus, left middle temporal gyrus, bilateral thalamus, left inferior frontal gyrus and right cerebellum. Mapping the abnormal patterns to the network atlas revealed the default mode network and the limbic system as core neural systems commonly affected in SLE. LIMITATIONS: The number of included studies is relatively small, with heterogeneous analytic methods and a risk of publication bias. CONCLUSIONS: Brain functional alterations in SLE are predominantly found in the default mode network and the limbic system. These findings uncovered a consistent pattern of resting-state functional network abnormalities in SLE which may serve as a potential objective neuroimaging biomarker.

Glymphatic System Impairment Contributes to the Formation of Brain Edema After Ischemic Stroke.

BACKGROUND: Blood-brain barrier damage has traditionally been considered to determine the occurrence and development of poststroke brain edema, a devastating and life-threatening complication. However, no treatment strategy targeting blood-brain barrier damage has been proven clinically effective in ameliorating brain edema. METHODS: In mice with stroke models induced by transient middle cerebral artery occlusion (MCAO), the changes in glymphatic system (GS) function impairment were detected by ex vivo fluorescence imaging, 2-photon in vivo imaging, and magnetic resonance imaging within 1 week after MCAO, and the effects of GS impairment and recovery on the formation and resolution of brain edema were evaluated. In addition, in patients with ischemic stroke within 1 week after onset, changes in GS function and brain edema were also observed by magnetic resonance imaging. RESULTS: We found that the extravasation of protein-rich fluids into the brain was not temporally correlated with edema formation after MCAO in mice, as brain edema reabsorption preceded blood-brain barrier closure. Strikingly, the time course of edema progression matched well with the GS dysfunction after MCAO. Pharmacological enhancement of the GS function significantly alleviated brain edema developed on day 2 after MCAO, accompanied by less deposition of Aß (amyloid-ß) and better cognitive function. Conversely, functional suppression of the GS delayed the absorption of brain edema on day 7 after MCAO. Moreover, patients with ischemic stroke revealed a consistent trend of GS dysfunction after reperfusion as MCAO mice, which was correlated with the severity of brain edema and functional outcomes. CONCLUSIONS: GS is a key contributor to the formation of brain edema after ischemic stroke, and targeting the GS may be a promising strategy for treating brain edema in ischemic stroke. REGISTRATION: URL: https://www.chictr.org.cn/showproj.html?proj=162857; Unique identifier: NFEC-2019-189.

One-dimensionally oriented self-assembly of ordered mesoporous nanofibers featuring tailorable mesophases via kinetic control.

One-dimensional (1D) nanomaterials have sparked widespread research interest owing to their fascinating physicochemical properties, however, the direct self-assembly of 1D porous nanomaterials and control over their porosity still presents a grand challenge. Herein, we report a monomicelle oriented self-assembly approach to fabricate 1D mesoporous nanostructures with uniform diameter, high aspect ratio and ordered mesostructure. This strategy features the introduction of hexamethylenetetramine as a curing agent, which can subtly control the monomicelle self-assembly kinetics, thus enabling formation of high-quality 1D ordered mesostructures. Meanwhile, the micellar structure can be precisely manipulated by changing the reactant stoichiometric ratio, resulting in tailorable mesophases from 3D cubic (Im-3m) to 2D hexagonal (p6mm) symmetries. More interestingly, the resultant mesoporous nanofibers can be assembled into 3D hierarchical cryogels on a large scale. The 1D nanoscale of the mesoporous nanofibers, in combination with small diameter (~65 nm), high aspect ratio (~154), large surface area (~452 m2 g-1), and 3D open mesopores (~6 nm), endows them with excellent performances for sodium ion storage and water purification. Our methodology opens up an exciting way to develop next-generation ordered mesoporous materials for various applications.

Self-Adaptive Droplet Bouncing on a Dual Gradient Surface.

Rapid detachment of impacting droplets from underlying substrate is highly preferred for mass, momentum, and energy exchange in many practical applications. Driven by this, the past several years have witnessed a surge in engineering macrotexture to reduce solid-liquid contact time. Despite these advances, these strategies in reducing contact time necessitate the elegant control of either the spatial location for droplet contact or the range of impacting velocity. Here, this work circumvents these limitations by designing a dual gradient surface consisting of a vertical spacing gradient made of tapered pillar arrays and a lateral curvature gradient characterized as macroscopic convex. This design enables the impacting droplets to self-adapt to asymmetric or pancake bouncing mode accordingly, which renders significant contact time reduction (up to ≈70%) for a broad range of impacting velocities (≈0.4-1.4 m s-1 ) irrespective of the spatial impacting location. This new design provides a new insight for designing liquid-repellent surfaces, and offers opportunities for applications including dropwise condensation, energy conversion, and anti-icing.

Achieving strong, stable, and durable underwater adhesives based on a simple and generic amino-acid-resembling design.

Developing underwater adhesives is important in many applications. Despite extensive progress, achieving strong, stable, and durable underwater adhesion via a simple and effective way is still challenging, mainly due to the conflict between the interfacial and bulk properties. Here, we report a unique bio-inspired strategy to facilely construct superior underwater adhesives with desirable interfacial and bulk properties. For adhesive design, a hydrophilic backbone is utilized to quickly absorb water for effective dehydration, and a novel amino acid-resembling functional block is developed to provide versatile molecular interactions for high interfacial adhesion. Moreover, the conjunction of these two components enables the generation of abundant covalent crosslinks for robust bulk cohesion. Such a rational design allows the adhesive to present a boosted underwater adhesion (3.92 MPa to glass), remarkable durability (maintaining high strength after one month), and good stability in various harsh environments (pH, salt, high temperature, and organic solvents). This strategy is generic, allowing the derivation of more similar adhesive designs easily and triggering new thinking for designing bio-inspired adhesives and beyond.

The early life course-related traits with three psychiatric disorders: A two-sample Mendelian randomization study.

Objectives: Several studies have indicated a potential association between early life course-related traits and neurological and psychiatric disorders in adulthood, but the causal link remains unclear. Methods: Instrumental variables (IVs) that have been shown to be strongly associated with exposure were obtained from summary data of genome-wide association studies (GWASs). Four early life course-related traits [i.e., birthweight (BW), childhood body mass index (BMI), early body size, and age at first birth (AFB)] were used as exposure IVs to estimate their causal associations with three neurological and psychiatric diseases [i.e., Alzheimer's disease (AD), major depressive disorder (MDD), and attention-deficit hyperactivity disorder (ADHD)]. Four different statistical methods, i.e., inverse-variance weighting (IVW), MR-Egger (MRE), weighted median (WM), and weighted mode (Wm), were performed in our MR analysis. Sensitivity analysis was performed by using the leave-one-out method, and horizontal pleiotropy was assessed using the MR-PRESSO package. Results: There was evidence suggesting that BW has a causal effect on AD (ORMR-PRESSO = 1.05, p = 1.14E-03), but this association was not confirmed via multivariable Mendelian randomization (MVMR) (ORMVMR = 0.97, 95% CI 0.92-1.02, p = 3.00E-01). A strong relationship was observed between childhood BMI and ADHD among both sexes; a 1-SD increase in BMI significantly predicted a 1.46-fold increase in the OR for ADHD (p = 9.13E-06). In addition, a similar relationship was found between early life body size and ADHD (ORMR-PRESSO = 1.47, p = 9.62E-05), and this effect was mainly driven by male participants (ORMR-PRESSO = 1.50, p = 1.28E-3). Earlier AFB could significantly predict a higher risk of MDD (ORMR-PRESSO = 1.19, p = 1.96E-10) and ADHD (ORMR-PRESSO = 1.45, p = 1.47E-15). No significant causal associations were observed between the remaining exposures and outcomes. Conclusion: Our results reveal the adverse effects of childhood obesity and preterm birth on the risk of ADHD later in life. The results of MVMR also show that lower BW may have no direct relationship with AD after adjusting for BMI. Furthermore, AFB may predict a higher risk of MDD.

Exceptional Hydrogen Diffusion Rate over Ru Nanoparticle-Doped Polar MgO(111) Surface.

Hydrogen (H) conductivity on oxide-based materials is crucially important in fuel cells and related catalysis. Here, this work measures the diffusion rate of H generated from Ru nanoparticles loaded on polar MgO(111) facet particles under H2 at elevated temperatures without moisture and compares it to conventional nonpolar MgO(110) for the first time by in situ quasielastic neutron scattering (QENS). The QENS reveals an exceptional diffusion rate on the polar facet via a proton (H+ ) hopping mechanism, which is an order of magnitude superior to that of typical H+ -conducting oxides. This work attributes this to the unique atomic arrangement of alternate layers of Mg cations and O anions of the polar MgO(111) where the strong electrostatic field of terminal oxygen anions facilitates protonic migration with a lower degree of local covalency.

Finger-inspired rigid-soft hybrid tactile sensor with superior sensitivity at high frequency.

Among kinds of flexible tactile sensors, piezoelectric tactile sensor has the advantage of fast response for dynamic force detection. However, it suffers from low sensitivity at high-frequency dynamic stimuli. Here, inspired by finger structure-rigid skeleton embedded in muscle, we report a piezoelectric tactile sensor using a rigid-soft hybrid force-transmission-layer in combination with a soft bottom substrate, which not only greatly enhances the force transmission, but also triggers a significantly magnified effect in d31 working mode of the piezoelectric sensory layer, instead of conventional d33 mode. Experiments show that this sensor exhibits a super-high sensitivity of 346.5 pC N-1 (@ 30 Hz), wide bandwidth of 5-600 Hz and a linear force detection range of 0.009-4.3 N, which is ~17 times the theoretical sensitivity of d33 mode. Furthermore, the sensor is able to detect multiple force directions with high reliability, and shows great potential in robotic dynamic tactile sensing.

Gestational diabetes mellitus suppresses fetal testis development in mice†.

The prevalence of gestational diabetes mellitus (GDM) is increasing rapidly. In addition to the metabolic disease risks, GDM might increase the risks of cryptorchidism in children. However, its mechanism involved in abnormalities of the male reproductive system is still unclear. The purpose of this study was to study the effects of GDM on the development of mouse fetal Leydig cells (FLCs) and Sertoli cells (SCs). Pregnant mice were treated on gestational days 6.5 and 12.5 with streptozotocin (100 mg/kg) or vehicle (sodium citrate buffer). Leydig cell and SC development and functions were evaluated by investigating serum testosterone levels, cell number and distribution, genes, and protein expression. GDM decreased serum testosterone levels, the anogenital distance, and the level of desert hedgehog in SCs of testes of male offspring. FLC number was also decreased in testes of GDM offspring by delaying the commitment of stem Leydig cells into the Leydig cell lineage. RNA-seq showed that FOXL2, RSPO1/ß-catenin signaling was activated and Gsk3ß signaling was inhibited in GDM offspring testis. In conclusion, GDM disrupted reproductive tract and testis development in mouse male offspring via altering genes related to development.

Developmental origins of adult diseases.

The occurrence and mechanisms of developmental adult diseases have gradually attracted attention in recent years. Exposure of gametes and embryos to adverse environments, especially during plastic development, can alter the expression of certain tissue-specific genes, leading to increased susceptibility to certain diseases in adulthood, such as diabetes, cardiovascular disease, neuropsychiatric, and reproductive system diseases, etc. The occurrence of chronic disease in adulthood is partly due to genetic factors, and the remaining risk is partly due to environmental-dependent epigenetic information alteration, including DNA methylation, histone modifications, and noncoding RNAs. Changes in this epigenetic information potentially damage our health, which has also been supported by numerous epidemiological and animal studies in recent years. Environmental factors functionally affect embryo development through epimutation, transmitting diseases to offspring and even later generations. This review mainly elaborated on the concept of developmental origins of adult diseases, and revealed the epigenetic mechanisms underlying these events, discussed the theoretical basis for the prevention and treatment of related diseases.

3D Printed, Solid-State Conductive Ionoelastomer as a Generic Building Block for Tactile Applications.

Shaping soft and conductive materials into preferential architectures via 3D printing is highly attractive for numerous applications ranging from tactile devices to bioelectronics. A landmark type of soft and conductive materials is hydrogels/ionogels. However, 3D-printed hydrogels/ionogels still suffer from a fundamental bottleneck: limited stability in their electrical-mechanical properties caused by the evaporation and leakage of liquid within hydrogels/ionogels. Although photocurable liquid-free ion-conducting elastomers can circumvent these limitations, the associated photocurable process is cumbersome and hence the printing quality is relatively poor. Herein, a fast photocurable, solid-state conductive ionoelastomer (SCIE) is developed that enables high-resolution 3D printing of arbitrary architectures. The printed building blocks possess many promising features over the conventional ion-conducting materials, including high resolution architectures (even ≈50 µm overhanging lattices), good Young's modulus (up to ≈6.2 MPa), and stretchability (fracture strain of ≈292%), excellent conductivity tolerance in a wide range of temperatures (from -30 to 80 °C), as well as fine elasticity and antifatigue ability even after 10 000 loading-unloading cycles. It is further demonstrated that the printed building blocks can be programmed into 3D flexible tactile sensors such as gyroid-based piezoresistive sensor and gap-based capacitive sensor, both of which exhibit several times higher in sensitivity than their bulky counterparts.

Design of ultra-stretchable, highly adhesive and self-healable hydrogels via tannic acid-enabled dynamic interactions.

Hydrogels have emerged as a landmark soft material for a wide range of applications such as in biomedical devices, soft robotics, artificial electronic skins, and the Internet of Things (IoT). To date, engineering hydrogels that simultaneously possess high stretchability (>3000%) and strong on-skin adhesion (>30 kPa) has not been an easy task. Generally, good stretchability is mainly dominated by the bulk interactions of hydrogels, whereas robust adhesion relies on the interfacial interactions of hydrogels with their surroundings. Here, we report a facile strategy to engineer an ultra-stretchable, highly adhesive and self-healable hydrogel, by virtue of tannic-acid-enabled dynamic interactions (TEDI) to fully substitute conventional covalent crosslinking. The TEDI strategy allows us to synchronously regulate both bulk and interfacial interactions to obtain exciting properties that outperform conventional hydrogels, including an extraordinary stretchability of over 7300%, remarkable self-healing abilities, and a robust on-skin adhesion of 50 kPa. With these intriguing merits, TEDI hydrogels are demonstrated to be a wearable strain sensor that accurately detect the motion of the human body. Moreover, our TEDI strategy unlocks new opportunities to design next-generation ionic hydrogels that may be valuable for applications in wearable electronic devices and healthcare monitoring.

Rapid Interchangeable Hydrogen, Hydride, and Proton Species at the Interface of Transition Metal Atom on Oxide Surface.

Hydrogen spillover is the phenomenon where a hydrogen atom, generated from the dissociative chemisorption of dihydrogen on the surface of a metal species, migrates from the metal to the catalytic support. This phenomenon is regarded as a promising avenue for hydrogen storage, yet the atomic mechanism for how the hydrogen atom can be transferred to the support has remained controversial for decades. As a result, the development of catalytic support for such a purpose is only limited to typical reducible oxide materials. Herein, by using a combination of in situ spectroscopic and imaging technique, we are able to visualize and observe the atomic pathway for which hydrogen travels via a frustrated Lewis pair that has been constructed on a nonreducible metal oxide. The interchangeable status between the hydrogen, proton, and hydride is carefully characterized and demonstrated. It is envisaged that this study has opened up new design criteria for hydrogen storage material.

Bisphenols and Leydig Cell Development and Function.

Bisphenol A (BPA) is a ubiquitous environmental pollutant, mainly from the production and use of plastics and the degradation of wastes related to industrial plastics. Evidence from laboratory animal and human studies supports the view that BPA has an endocrine disrupting effect on Leydig cell development and function. To better understand the adverse effects of BPA, we reviewed its role and mechanism by analyzing rodent data in vivo and in vitro and human epidemiological evidence. BPA has estrogen and anti-androgen effects, thereby destroying the development and function of Leydig cells and causing related reproductive diseases such as testicular dysgenesis syndrome, delayed puberty, and subfertility/infertility. Due to the limitation of BPA production, the increased use of BPA analogs has also attracted attention to these new chemicals. They may share actions and mechanisms similar to or different from BPA.

In utero cadmium and dibutyl phthalate combination exposure worsens the defects of fetal testis in rats.

Testicular dysgenesis syndrome might be due to the fetal testis defects caused by endocrine disruptors. Here, we report the combined effects of in utero exposure to cadmium (CdCl2, Cd) and di-n-butyl phthalate (DBP) on fetal testis development in rats. Pregnant Sprague-Dawley rats were randomly divided into four groups: control, Cd, DBP (250 mg/kg/day), and Cd + DBP. Cd (0.25 mg/kg/once) was intraperitoneally injected to the dam on gestational day 12 and DBP (250 mg/kg) was daily gavaged to the dam on gestational day 12 for 10 days. Cd, DBP, and Cd + DBP lowered serum testosterone levels in male fetuses. Cd and DBP did not alter fetal Leydig cell (FLC) number, but the combined exposure led to decreased FLC number. Cd did not affect FLC aggregation while DBP caused FLC aggregation and the combined exposure worsened FLC aggregation. Cd lowered FLC mRNA (Lhcgr, Star, Cyp11a1, and Insl3) levels and DBP lowered Lhcgr, Star, Insl3, and Nr5a1 levels. DBP up-regulated Scarb1 expression without affecting Cyp11a1 while the combined exposure antagonized DBP. These two chemicals and its combination did not affect Sertoli cell number and gene (Amh, Fshr, and Sox9) expression at current doses. In conclusion, the combined exposure of Cd and DBP exerts synergically antiandrogenic effects via targeting FLC development.

Perfluoroalkyl substances cause Leydig cell dysfunction as endocrine disruptors.

Perfluoroalkyl substances (PFASs) are a group of man-made organic substances. Some of PFASs have been classified as persistent organic pollutants and endocrine disruptors. They might interfere with the male sex endocrine system, causing the abnormal development of the male reproductive tract and failure of pubertal onset and infertility. The present review discusses the development and function of two generations of Leydig cells in rodents and the effects of PFASs on Leydig cell development after their exposure in gestational and postnatal periods. We also discuss human epidemiological data for the effects of PFASs on male sex hormone levels. The structure-activity relationship of PFASs on Leydig cell steroidogenesis and enzyme activities are also discussed.