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Wood-based solar steam evaporators have been attracting increasing interest due to their great potential for addressing water scarcity by utilizing sustainable materials and energy. However, engineering a 3D porous structure within the wood lumens and its effect on solar vapor evaporation have not yet been well explored. Here, a natural wood-based solar evaporator with hierarchical pores is fabricated by assembling polyvinyl alcohol within the lumens through an ice-templating approach. The polyvinyl alcohol porous network is engineered from vertically aligned microchannels to dendritically bridged pores with a narrowed size of a few micrometers and significantly increased surface area. Although the formation of plenty of microscopic channels increases the capillary force in comparison to the native wood lumen, the morphology change induces a high tortuosity factor of the porous structure, resulting in a reduced water transportation rate as well as an increased contact angle. On the other hand, the high surface area of the engineered wood lumens and the good hydrophilicity of the filled polyvinyl alcohol improve the ratio of the formed intermediate water, contributing to reduced vaporization enthalpy. Consequently, by using polydopamine as the photothermal material, the hierarchically structured polyvinyl alcohol-wood solar evaporator exhibits an evaporation rate of 1.6 kg m

Objectives Derivation and maintenance of pluripotent stem cells (PSCs) generally require optimized and complex culture media, which hinders the derivation of PSCs from various species. Expression of Oct4, Sox2, Klf4, and c‐Myc (OSKM) can reprogram somatic cells into induced PSCs (iPSCs), even for species possessing no optimal culture condition. Herein, we explored whether expression of OSKM could induce and maintain pluripotency without PSC‐specific growth factors and signaling inhibitors. Methods The culture medium of Tet‐On‐OSKM/Oct4‐GFP mouse embryonic stem cells (ESCs) was switched from N2B27 with MEK inhibitor, GSK3β inhibitor, and leukemia inhibitory factor (LIF) (2iL) to N2B27 with doxycycline. Tet‐On‐OSKM mouse embryonic fibroblast (MEF) cells were reprogrammed in N2B27 with doxycycline. Cell proliferation was traced. Pluripotency was assessed by expression of ESC marker genes, teratoma, and chimera formation. RNA‐Seq was conducted to analyze gene expression. Results Via continuous expression of OSKM, mouse ESCs (OSKM‐ESCs) and the resulting iPSCs (OSKM‐iPSCs) reprogrammed from MEF cells propagated stably, expressed pluripotency marker genes, and formed three germ layers in teratomas. Transcriptional landscapes of OSKM‐iPSCs resembled those of ESCs cultured in 2iL and were more similar to those of ESCs cultured in serum/LIF. Furthermore, OSKM‐iPSCs contributed to germline transmission. Conclusions Expression of OSKM could induce and maintain mouse pluripotency without specific culturing factors. Importantly, OSKM‐iPSCs could produce gene‐modified animals through germline transmission, with potential applications in other species., The requirement of optimized and complex culture media for obtaining and maintaining pluripotent stem cells (PSCs) hinders stem cell research. Here, Mao et al report that continuous expression of reprogramming factors OSKM induces and maintains mouse pluripotency without specific culturing factors. Importantly, the resulting iPSCs can produce gene‐edited animals via germline transmission, possessing a potential application in other species.

Understanding human development is of fundamental biological and clinical importance. Yet despite its significance, insights into early developmental events in humans still remain largely unknown. While recent advances show that stem cells can mimic embryogenesis1–9to unravel hidden developmental mechanisms, a stem cell-based model of early human embryogenesis is lacking. Here, we use human extended pluripotent stem cells10to reconstitute early human development in 3-dimensions and recapitulate early embryo-like events. We first perform a systematic characterisation to reveal unique signalling requirements for building the human pre-implantation blastocyst. Further, we show that thesein vitrostem cell-derived blastocyst-like structures are able to undertake spatiotemporal self-organisation to mimic peri-implantation remodelling in which a polarised rosette opens up the amniotic cavity within a developing disc. The hallmarks of human early development displayed by this stem cell-basedin vitromodel mimics features of embryonic day 3 to day 9/10 of natural development. Thus, this platform represents a tractable model system to contribute to the basic understanding of cellular and molecular mechanisms governing early embryonic events in humans and to provide valuable insights into the design of differentiation protocols for human stem cells in clinical applications.

Infertile people who suffered from loss of uterine structures and/or functions can be treated through gestational surrogacy or uterus transplantation, which remains challenging due to the ethical and social issues, the lack of donor organs as well as technical and safety risks. One promising solution is to regenerate and reconstruct a bioartificial uterus for transplantation through the engineering of uterine architecture and appropriate cellular constituents. Here, we developed a well-defined system to regenerate a functional rat uterine through recellularization of the decellularized uterine matrix (DUM) patches reseeded with human mesenchymal stem cells (hMSCs). Engraftment of the recellularized DUMs on the partially excised uteri yielded a functional rat uterus with a pregnancy rate and number of fetuses per uterine horn comparable to that of the control group with an intact uterus. Particularly, the recellularized DUMs enhanced the regeneration of traumatic uterine in vivo because of MSC regulation. The established system here will shed light on the treatment of uterine infertility with heterogeneous DUMs/cell resources through tissue engineering in the future.

Early human post-implantation development involves extensive growth combined with a series of complex morphogenetic events. The lack of precise spatial and temporal control over these processes leads to pregnancy loss. Given the ethical and technical limitations in studying the natural human embryo, alternative approaches are needed to investigate mechanisms underlying this critical stage of human development. Here, we present an overview of the different stem cells and stem cell-derived models which serve as useful, albeit imperfect, tools in understanding human embryogenesis. Current models include stem cells that represent each of the three earliest lineages: human embryonic stem cells corresponding to the epiblast, hypoblast-like stem cells and trophoblast stem cells. We also review the use of human embryonic stem cells to model complex aspects of epiblast morphogenesis and differentiation. Additionally, we propose that the combination of both embryonic and extra-embryonic stem cells to form three-dimensional embryo models will provide valuable insights into cell-cell chemical and mechanical interactions that are essential for natural embryogenesis.

Understanding the relationship between multiphase structure and electromechanical property of thermoplastic dielectric elastomers is significantly important in the developments of high-performance and novel dielectric elastomers. In this work, we fabricated a series of aliphatic polyurethane elastomers (PUEs) based on hydroxyl-terminated butadiene-acrylonitrile copolymer (HTBN), hexamethylene diisocyanate (HDI), and various lengths of linear aliphatic diols and investigated effect of their microstructure and morphology on dielectric and electromechanical properties. The FTIR, WAXS, SAXS, and viscoelastic AFM results showed that the PUEs existed in crystalline phase, hard domain (HD) and soft domain (SD) phases composed HD-rich region and few HDs and SD composted SD-rich region by crystallization and microphase separation. Also, the crystal morphology and crystallinity of PUEs are strongly influenced by the length of chain extender due to the chain extender adopting various conformations by hydrogen bondin...

High dielectric constant and low modulus of thermoplastic polyurethane elastomers (PUEs) are required for various applications in actuators, sensors and energy harvestings. In this work, we controlled the microphase separated morphology of PUEs by regulation of the content of hydroxyl-terminated four-armed polycaprolactone (4amPCL) chain extender to achieve J-shaped stress-strain curve with low modulus and high electromechanical properties. Our results showed that the hydrogen bonding between hard segments (HSs) and crystallization of soft segment (SS) are significantly impeded by long-chain branched structure when added lower molar fraction ( 20% of chain extenders) of 4amPCL as chain extender. The PUE with 29% of 4amPCL (PU-4amPCL-0.29) showed lower modulus (1.5 MPa), higher tensile strength (17.5 MPa) at 1048% of elongation, and 3.9% of actuation strain at 20 kV/mm, and higher contribution (48.1%) of Maxwell stress on actuation strain at 20 kV/mm. We found that the microphase separation of branched long-chains induced semi-interpenetration polymer network like structure of PUEs played an important role in exhibiting J-shaped stress-strain behavior. Our results can provide new insight on fabrication of high electromechanical performance of dielectric polyurethane elastomers.

Figure S1. Non-specific DNase activity is conserved across Cas12 proteins. Figure S2. The RuvC domain is responsible for ssDNA trans-cleavage. Figure S3. Preference for Cas12b-mediated trans-activated cleavage of non-specific ssDNA. Figure S4. Sensitivity and specificity of AaCas12b-mediated DNA detection. Figure S5. Comparison of sensitivity of AaCas12b- and LbCas12a-based DNA detection. Figure S6. CDetection achieves sub-attomolar sensitivity in DNA detection. Figure S7. Develop CDetection platform. Figure S8. Accurate DNA detection using CDetection platform. Figure S9. Potential off-target analysis of CDetection. Figure S10. Rapid and accurate diagnostic applications of CDetection. Figure S11. Genetic variants from ClinVar that, in principle, can be detected by CDetection platform. (PDF 2218 kb)

Table S2. Sequences of targeting crRNAs used for in vitro RNA transcription. Table S3. Target sequences harboring various 5â ˛ PAM sequences used for in vitro DNA cleavage assay. Table S4. Protospacer sequences used for genome editing. Table S5. crRNA scaffold optimization and screening. Table S6. Primer sequences used for PCR amplification. Table S7. Frequency of Cas12a- and SpCas9-mediated targeted indel mutations at on-target sites in human 293FT cells. Table S8. Off-target analysis by targeted deep sequencing in the human 293FT cells. Table S9. Off-target analysis by whole genome sequencing (WGS) in human 293FT cells. (PDF 395 kb)

Supplementary Sequences. The humanized Cas12a coding sequences, protein sequences, U6-crRNA backbone sequences, mammalian and prokaryotic expression vector sequences used in this study. (PDF 183 kb)

Table S1. Nucleic acids used in this study. Table S2. The components of buffers tested for Cas12b-mediated DNA detection in this study. (PDF 293 kb)

Supplementary methods. (PDF 124 kb)

Review history. (DOCX 1323 kb)

The prokaryotic CRISPR-Cas adaptive immune systems provide valuable resources to develop genome editing tools, such as CRISPR-Cas9 and CRISPR-Cas12a/Cpf1. Recently, CRISPR-Cas12b/C2c1, a distinct type V-B system, has been characterized as a dual-RNA-guided DNA endonuclease system. Though being active in vitro, its cleavage activity at endogenous genome remains to be explored. Furthermore, the optimal cleavage temperature of the reported Cas12b orthologs is higher than 40 °C, which is unsuitable for mammalian applications. Here, we report the identification of a Cas12b system from the Alicyclobacillus acidiphilus (AaCas12b), which maintains optimal nuclease activity over a wide temperature range (31 °C–59 °C). AaCas12b can be repurposed to engineer mammalian genomes for versatile applications, including single and multiplex genome editing, gene activation, and generation of gene mutant mouse models. Moreover, whole-genome sequencing reveals high specificity and minimal off-target effects of AaCas12b-meditated genome editing. Our findings establish CRISPR-Cas12b as a versatile tool for mammalian genome engineering.

哺乳动物的雌性生殖道包括输卵管、子宫、宫颈和阴道, 是卵子受精、早期胚胎发育、胚胎着床、孕体发育和分娩等的重要路径, 对于哺乳动物的生殖非常重要. 雌性生殖器官的发育异常和病变将导致妊娠失败和胎儿死亡, 因而了解雌性生殖道的发育过程和分子调节机制有利于理解生殖相关疾病和改善雌性生殖力. 目前, 利用基因敲除小鼠等多种实验技术, 人们发现了调节雌性生殖道发育和导致生殖道疾病的部分关键基因和调节机理, 本文将总结近年来雌性生殖道的发育分子调控机制方面的研究进展, 并阐述多种信号通路在生殖道发育过程中的交叉调节网络.

Human embryonic stem cells contribute to embryonic and extraembryonic lineages in mouse embryos upon inhibition of apoptosis

Pluripotency of embryonic stem cells (ESCs) can be functionally assessed according to the developmental potency. Tetraploid complementation, through which an entire organism is produced from the pluripotent donor cells, is taken as the most stringent test for pluripotency. It remains unclear whether ESCs of other species besides mice can pass this test. Here we show that the rat ESCs derived under 2i (two small molecule inhibitors) conditions at very early passages are able to produce fertile offspring by tetraploid complementation. However, they lose this capacity rapidly during culture due to a nearly complete loss of genomic imprinting. Our findings support that the naive ground state pluripotency can be captured in rat ESCs but also point to the species-specific differences in its regulation and maintenance, which have implications for the derivation and application of naive pluripotent stem cells in other species including human.

Formation of secretary endometrial glands in the uterus known as adenogenesis is a typical process of branching morphogenesis involving dynamic epithelial growth and differentiation. Unsuccessful adenogenesis often leads to female infertility. However, it remains largely unexplored so far regarding the epigenetic machinery governing normal endometrial gland formation. Here, we demonstrated that PR-Set7, an epigenetic regulator for H4K20me1 modification, was extensively expressed in the postnatal uteri, and its conditional deletion resulted in a complete lack of endometrial glands and infertility in mice. Subsequent analysis revealed that uterine PR-Set7 deficiency abolishes the dynamic endometrial epithelial population growth during the short span of gland formation from postnatal days 3 to 9. This markedly reduced epithelial population growth in PR-Set7-null mutant uteri is well associated with DNA damage accumulation and massive apoptotic death in the epithelium, due to blockade of 53BP1 recruitment to DNA damage sites upon reduced levels of H4K20me1/2. Using PgrCre/+/Rosa26DTA/+ mouse line and postnatal progesterone injection mouse model, we further confirmed that an impaired epithelial cell population growth either by inducing epithelial death in the diphtheria toxin-A (DTA)-mouse model or attenuating epithelial growth upon postnatal progesterone treatment similarly hampers uterine adenogenesis. Collectively, we establish here a novel ‘epithelial population growth threshold’ model for successful gland development. Besides further shedding light on the regulatory machinery governing uterine gland formation, our findings raise a safety concern on progesterone supplementation to prevent preterm birth in women bearing a female fetus, as exogenous progesterone may hamper uterine adenogenesis via attenuating epithelial population growth.

Estrogens and androgens play important roles in regulating the hormone-secreting functions of the pituitary gland by binding to their corresponding receptors. However, the expression of estrogen receptors (ERs) and the androgen receptor (AR) and the cell types containing ERs and AR in the anterior pituitary gland of adult chickens have not been well-studied. In this study, the distribution of ERα, AR and their corresponding cell types in the anterior pituitary gland of adult cockerels was detected by immunohistochemistry. The results showed that ERα was expressed in 68.63 % of luteinizing hormone (LH) producing cells but was not found in thyrotropes, lactotropes, somatotropes, corticotropes and folliculo-stellate (FS) cells. Pituitary hormone and AR double labeling results showed that about 37 % of LH cells and 50 % of thyroid-stimulating hormone (TSH) producing cells expressed AR, respectively. In contrast, less than 1 % of the somatotropes had an AR positive signal and AR signals were not detected in lactotropes, corticotropes or FS cells. In addition, there were only a few AR and ERα dual-labeled cells observed. These novel results provide evidence for a cell-specific distribution of ERα and AR in the anterior pituitary from adult cockerels by immunohistochemistry. The different distributions of ERα and AR in the LH cells suggest that the feedback-regulating mechanisms of estrogen and androgen on the pituitary hormones secretion are different. The functions and related mechanisms still need to be elucidated further.

The aim of this work is to prospectively assess the relationship between trans-laminar cribrosa pressure difference and neuroretinal rim area as morphologic surrogate of glaucomatous optic nerve damage.The study included 22 patients with high-pressure glaucoma, 13 patients with normal-pressure glaucoma, and 17 subjects with ocular hypertension. All participants underwent a standardized ophthalmologic examination including confocal laser scanning tomography of the optic nerve head and computerized perimetry and a neurologic examination including measurement of the lumbar cerebrospinal fluid (CSF) pressure. The trans-lamina cribrosa pressure difference was calculated as difference of intraocular pressure minus lumbar CSF pressure.Neuroretinal rim area (p = 0.006; correlation coefficient r = -0.38) and mean visual field defect (p = 0.008; r = 0.38) were significantly associated with trans-lamina cribrosa pressure difference. The probability of error was lower (i.e., the p value were lower) and the correlation coefficients were higher for the associations between rim area/visual field defect with trans-lamina cribrosa pressure difference than for the associations between rim area/visual field defect and intraocular pressure or lumbar CSF pressure.The trans-lamina cribrosa pressure difference as the difference of intraocular pressure minus the lumbar CSF pressure was the main pressure parameter associated with the amount of glaucomatous optic nerve damage. This may suggest that the CSF pressure as trans-lamina cribrosa counter pressure against the intraocular pressure may play some role in the pathogenesis of glaucomatous optic neuropathy.

The objective of this study was to investigate the feasibility of recovering the polyols from the polyurethane (PU) foam obtained from waste upholstered furniture (sofa) by chemical decomposition using the propylene glycol (PPG) as the decomposing solvent and sodium hydroxide (NaOH) as the catalyst, respectively. The effects of temperature (180°C and 200°C), reaction time (0.5, 1, 1.5, 2, 2.5, and 3 hours), and PPG/PU weight ratio (2:1, 3:1, and 4:1) on the decomposition reaction and the physicochemical properties of the recovered polyols, such as hydroxyl number, viscosity, and amine number were investigated. Higher temperature and PPG/PU weight ratio promoted the PU decomposition reaction and resulted in lower viscosity, higher hydroxyl number, and higher amine number of the recovered polyols. The hydroxyl number and amine number increased as the reaction progressed, while the viscosity decreased. Once the reaction was completed, little change was observed for the hydroxyl number and viscosity of the recovered polyols. The recovered polyol obtained at 200°Cand PPG/PU weight ratio of 3:1 showed about the same length of time for the reaction, as well as the physical properties to that obtained at 180°C and PPG/PU weight ratio of 4:1. These recovered polyols had similar hydroxyl number and viscosity to those of commercial polyol used for PU coatings, elastomers, adhesives, and sealants.

The objective of this study was to investigate the feasibility of using recycled polyols as part of the binder system for wood panels (fiberboard). PU foam wastes from disposed insulation materials were collected, processed, and chemically decomposed by agent to obtain the recycled polyol. The recycled polyol was mixed with a commercial polyol at various weight ratios (0: 100, 20: 80, 40: 60, 60: 40, 80: 20, and 100: 0) to prepare a series of polyol mixtures. Then, the obtained polyol mixtures were then sprayed successively with pMDI resin at various pMDI/polyol mixtures weight ratios (100: 0, 75: 25, and 50: 50) onto wood fibers to prepare fiberboards. The effects of recycled polyol/commercial polyol weight ratio and pMDI/polyol mixture weight ratio on physical and mechanical properties of bonded fiberboards were evaluated. The results showed that the addition of recycled polyol into a commercial polyol helped improve the IB, MOR, and MOE strength of fiberboard, but their effects on water resistance of fiberboard were minor. With the increase of percentage of polyol mixture in pMDI/polyol mixture, the properties of fiberboard presented a trend of decreasing. When the recycled polyol/commercial polyol weight ratio was 40: 60 and the pMDI/polyol mixture was 25: 75, the bonded fiberboard had the overall best physical and mechanical performances. The application of decomposed PU foams in fiberboard production provided a new possible way of recycling polymer wastes.

The objective of this study was to investigate the feasibility of using polyurethane (PU) foam wastes obtained from automobile shredder residue (ASR) in wood composite panel (fiberboard) production. PU foam wastes from ASR were picked by hand, cleaned by water and acetone, grounded into powders of two sizes (60 mesh and 120 mesh), and dried to remove moisture. The PU powders were characterized by stereomicroscope and then partially replaced pMDI resin at percentages of 10%, 20%, 30%, 40%, and 50% (based on the weight of pMDI resin). The PU powders were mixed with wood fibers to make fiberboards. The results showed that the addition of PU powders increased both the physical and mechanical properties of fiberboards. At replacing percentages from 5% to 30%, the properties of fiberboards increased. However, further increase of replacing percentages (from 30% to 50%) resulted in lower properties of fiberboard. When observed at a magnification of 125 times by a stereomicroscope, PU powders of 60 mesh had more foam features while PU powders of 120 mesh had more particle features. The fiberboards bonded by pMDI resin and PU powders of 120 mesh had better water resistance and mechanical properties than those bonded by pMDI and PU powders of 60 mesh. The use of PU powders in fiberboard production provided a new possible way of recycling PU foam wastes. The fiberboard has advantages of formaldehyde-free, better water resistance, higher mechanical properties, and lower material cost.

To examine in an intra-individual comparison whether cataract is associated with age-related macular degeneration (AMD).The population-based Beijing Eye Study included 4,439 subjects (age: 40+ years) out of 5,324 subjects invited to be examined. Using lens and fundus photographs, the amount of AMD was graded according to the Wisconsin Age-Related Maculopathy Grading system and the degree of cataract was graded using the system of the Age-Related Eye Disease Study.Photographs with sufficient quality for bilateral examination of the lens and macula were available for 3,826 (86.2%) participants with a mean age of 55.3 ± 10.0 years (range: 40-90 years) and a mean refractive error of -0.38 ± 2.18 diopters (range: -20.13 diopters to +7.50 diopters). The side difference in presence of early AMD and late AMD respectively was not significantly associated with the inter-eye difference in the amount of nuclear cataract [P = 0.27 and P = 0.28 (r = 0.02) respectively), amount of cortical cataract (P = 0.12 and P = 0.05 respectively), and amount of subcapsular posterior cataract (P = 0.91 and P = 0.85 respectively). In a similar manner, the side difference in the presence of early AMD and late AMD was not significantly associated with the inter-eye difference in the presence of nuclear cataract (P = 0.99 and P = 0.99 respectively), cortical cataract (P = 0.25 and P = 1.00 respectively), and subcapsular posterior cataract (P = 0.59 and P = 0.05 respectively). The side difference in the number of macular drusen was not significantly associated with the inter-eye difference in the amount of nuclear cataract (P = 0.74), amount of cortical cataract (P = 0.19) and amount of subcapsular posterior cataract (P = 0.88). As a corollary, unilateral pseudophakia or aphakia was not significantly associated with inter-eye differences in the count (P = 0.59) of drusen, and overall presence of early AMD (P = 0.99) or late AMD (P = 0.99).In an intra-individual, inter-eye comparison, avoiding interdependencies of systemic parameters, inter-eye difference was not significantly associated with any characteristics of age-related macular degeneration in either any type of cataract or in pseudophakia. This suggests that the development of cataract or cataract surgery did not markedly influence the development of age-related macular degeneration.

Purpose To assess the relationship of hypertension with major eye diseases and other ocular parameters. Design Population-based study. Participants The Beijing Eye Study is a population-based study that included 4439 Chinese subjects examined at the baseline examination in 2001; there was a follow-up examination in 2006, in which 3251 subjects participated, of whom 3222 had blood pressure measurements. Methods All participants underwent an ophthalmic examination, anthropometric measurements, and blood pressure measurement. Hypertension was defined as a systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, and/or self-reported current treatment for hypertension with antihypertensive medication. Main Outcome Measures Blood pressure and ocular parameters, including intraocular pressure and prevalence of major ophthalmic diseases. Results Mean age of participants in the present study was 60.4±10.0 years. Hypertension was present in 1500 (46.6%) of the 3222 subjects who had their blood pressure measured. In multiple regression analysis, hypertension was associated with higher intraocular pressure (β = 0.39; 95% confidence interval [CI], 0.12–0.66; P = 0.005), focal arteriolar narrowing (odds ratio [OR], 1.78; 95% CI, 1.34–2.36; P P = 0.009), generalized retinal arteriolar narrowing (OR, 1.65; 95% CI, 1.30–2.09; P P = 0.02), and diabetic retinopathy (OR, 1.90; 95% CI, 1.08–3.31; P = 0.02). Hypertension was not significantly associated with the prevalence of open-angle glaucoma ( P = 0.19), angle-closure glaucoma ( P = 0.15), age-related macular degeneration (AMD) ( P = 0.73), nuclear cataract ( P = 0.88), posterior subcapsular cataract ( P = 0.30), cortical cataract ( P = 0.10), or area of alpha zone ( P = 0.05) or beta zone of parapapillary atrophy ( P = 0.95). Conclusions In Chinese persons, while controlling for other systemic parameters, hypertension was associated with increased intraocular pressure, retinal microvascular abnormalities, and prevalence of retinal vein occlusion and diabetic retinopathy. Hypertension was not associated significantly with AMD, age-related cataract, or glaucoma. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Uterine decidualization characterized by stromal cell proliferation and differentiation is critical to the establishment of pregnancy in many species. Progesterone is a key factor in regulating endometrial cell decidualization, however, the molecular basis involved in mediating the effects of progesterone during decidualization remains largely unknown. We report here that the DNA replication licensing factor MCM2, one of the conserved set of six-related proteins (MCM complex: MCM2-7) essential for eukaryotic DNA replication, is dynamically expressed in both proliferative and differentiated stromal cells during mouse periimplantation uterus. Applying PR-knockout mouse model and pharmacological strategy, we further found that the expression of Mcm2 is induced by progesterone action in the mouse uterine stroma. Employing a primary cell culture system, we further demonstrated that siRNA-mediated silencing of MCM2 arrests the cell cycle at G1-S transition during stromal cell proliferation. Moreover, the downregulation of Mcm2 could also compromise stromal cell differentiation. Collectively, our studies uncovered the role of a unique DNA replication licensing molecule MCM2 in mediating Progesterone-induced stromal cell decidualization in mouse uterus.

Human endometrium decidualization, which involves endometrial stromal proliferation and differentiation, is a prerequisite for embryo implantation, thus successful pregnancy. The Forkhead Box M1 (FoxM1), previously known as HNF-3, HFH-11, MPP2, Win and Trident, is a transcriptional factor that plays crucial roles in cell proliferation and cell cycle progression. However, the molecular mechanism of FoxM1 during human endometrial decidualization remains unexplored. In this study, we first found FoxM1 is dynamically expressed in human endometrium during menstrual cycle. Employing a human endometrial stromal cell (HESC) line, we then demonstrated that FoxM1 inhibition downregulates cyclin B1 expression, delaying G2/M phase transition during HESC proliferation. Additionally, loss of FoxM1 expression blocks the differentiation of HESCs in response to estrogen, progesterone and dbcAMP. Applying chromatin immunoprecipitation (ChIP) technique and luciferase assay, we further approved that FoxM1 can transcriptionally active signal transducer and activator of transcription 3 (STAT3), ensuring normal HESC differentiation. Besides enriching our knowledge on molecular basis underlying stromal decidualization, these findings help to shed light on the potential molecular causes for the endometrial disorders in humans.

Successful embryo implantation requires functional luminal epithelia to establish uterine receptivity and blastocyst-uterine adhesion. During the configuration of uterine receptivity from prereceptive phase, the luminal epithelium undergoes dynamic membrane reorganization and depolarization. This timely regulated epithelial membrane maturation and precisely maintained epithelial integrity are critical for embryo implantation in both humans and mice. However, it remained largely unexplored with respect to potential signaling cascades governing this functional epithelial transformation prior to implantation. Using multiple genetic and cellular approaches combined with uterine conditional Rac1 deletion mouse model, we demonstrated herein that Rac1, a small GTPase, is spatiotemporally expressed in the periimplantation uterus, and uterine depletion of Rac1 induces premature decrease of epithelial apical-basal polarity and defective junction remodeling, leading to disrupted uterine receptivity and implantation failure. Further investigations identified Pak1-ERM as a downstream signaling cascade upon Rac1 activation in the luminal epithelium necessary for uterine receptivity. In addition, we also demonstrated that Rac1 via P38 MAPK signaling ensures timely epithelial apoptotic death at postimplantation. Besides uncovering a potentially important molecule machinery governing uterine luminal integrity for embryo implantation, our finding has high clinical relevance, because Rac1 is essential for normal endometrial functions in women.

The aim of the study was to evaluate the prevalence of under-corrected refractive error among elderly Chinese in the Beijing area.The population-based, cross-sectional, cohort study comprised 4,439 subjects out of 5,324 subjects asked to participate (response rate 83.4%) with an age of 40+ years. It was divided into a rural part [1,973 (44.4%) subjects] and an urban part [2,466 (55.6%) subjects]. Habitual and best-corrected visual acuity was measured. Under-corrected refractive error was defined as an improvement in visual acuity of the better eye of at least two lines with best possible refractive correction.The rate of under-corrected refractive error was 19.4% (95% confidence interval, 18.2, 20.6). In a multiple regression analysis, prevalence and size of under-corrected refractive error in the better eye was significantly associated with lower level of education (P0.001), female gender (P0.001), and age (P=0.001).Under-correction of refractive error is relatively common among elderly Chinese in the Beijing area when compared with data from other populations.

To assess the relationship of hypertension with major eye diseases and other ocular parameters.Population-based study.The Beijing Eye Study is a population-based study that included 4439 Chinese subjects examined at the baseline examination in 2001; there was a follow-up examination in 2006, in which 3251 subjects participated, of whom 3222 had blood pressure measurements.All participants underwent an ophthalmic examination, anthropometric measurements, and blood pressure measurement. Hypertension was defined as a systolic blood pressureor=140 mmHg and/or diastolic blood pressureor=90 mmHg, and/or self-reported current treatment for hypertension with antihypertensive medication.Blood pressure and ocular parameters, including intraocular pressure and prevalence of major ophthalmic diseases.Mean age of participants in the present study was 60.4+/-10.0 years. Hypertension was present in 1500 (46.6%) of the 3222 subjects who had their blood pressure measured. In multiple regression analysis, hypertension was associated with higher intraocular pressure (beta = 0.39; 95% confidence interval [CI], 0.12-0.66; P = 0.005), focal arteriolar narrowing (odds ratio [OR], 1.78; 95% CI, 1.34-2.36; P0.001), arteriovenous nicking (OR, 1.50; 95% CI, 1.11-2.04; P = 0.009), generalized retinal arteriolar narrowing (OR, 1.65; 95% CI, 1.30-2.09; P0.001), retinal vein occlusions (OR, 2.86; 95% CI, 1.21-6.80; P = 0.02), and diabetic retinopathy (OR, 1.90; 95% CI, 1.08-3.31; P = 0.02). Hypertension was not significantly associated with the prevalence of open-angle glaucoma (P = 0.19), angle-closure glaucoma (P = 0.15), age-related macular degeneration (AMD) (P = 0.73), nuclear cataract (P = 0.88), posterior subcapsular cataract (P = 0.30), cortical cataract (P = 0.10), or area of alpha zone (P = 0.05) or beta zone of parapapillary atrophy (P = 0.95).In Chinese persons, while controlling for other systemic parameters, hypertension was associated with increased intraocular pressure, retinal microvascular abnormalities, and prevalence of retinal vein occlusion and diabetic retinopathy. Hypertension was not associated significantly with AMD, age-related cataract, or glaucoma.

To evaluate the causes of visual impairment and blindness in adult Chinese in an urban and rural region of Beijing, China.Population-based prevalence survey.From a rural region and an urban region of Greater Beijing, 4439 of 5324or=40-year-old invited subjects participated in the study (response rate, 83.4%). Using the World Health Organization (WHO) standard and the United States standard, blindness was defined as best-corrected visual acuity (BCVA) in the better-seeing eye of20/400 and of2/20, respectively, and visual impairment was defined as best-corrected vision of20/60 andor =20/400, and of20/40 andor =2/20, respectively.Determination of BCVA, pneumotonometry, frequency doubling perimetry, evaluation of photographs of the fundus and lens, and clinical examination.Causes of visual impairment and blindness.Visual acuity measurements were available for 8816 eyes of 4409 subjects (99.3%). Using the WHO standard and the U.S. standard, 49 (1.1%) subjects and 95 (2.2%) subjects, respectively, had low vision, and 13 (0.3%) subjects and 15 (0.3%) subjects, respectively, were blind by definition. Taking the whole study population, the most frequent cause of low vision/blindness was cataract (36.7%/38.5%), followed by degenerative myopia (32.7%/7.7%), glaucoma (14.3%/7.7%), corneal opacity (6.1%/15.4%), and other optic nerve damage (2.0%/7.7%). Age-related macular degeneration (AMD) (2.0%/7.7%) and diabetic retinopathy (0%/7.7%) were responsible for a minority of cases. In subjects 40 to 49 years old, the most frequent cause of low vision and blindness was degenerative myopia. In the 50- to 59-year age group, the most frequent cause was cataract, followed by degenerative myopia. In the 60- to 69-year-old subjects and theor =70-year group, the most frequent cause of low vision and blindness was cataract, followed by degenerative myopia and glaucoma.The most frequent cause of low vision and blindness in adult Chinese is cataract, followed by degenerative myopia and glaucomatous optic neuropathy, with degenerative myopia dominating in younger groups and cataract dominating in elder groups. In contrast to studies in Western countries, AMD and diabetic retinopathy appear to play a minor role as a cause of visual impairment in elderly Chinese.

To estimate the prevalence and distribution of blindness and low vision in Northern China.Population-based cohort study.The Beijing Eye Study included 4438 subjects with an age of 40+ years. Mean age was 56.2 +/- 10.6 years (range, 40 to 101 years).Forty-three (1.0%) individuals had low vision (20/60 and/=20/400 best-corrected vision), and 17 (0.4%) individuals were blind (best-corrected visual acuity in the better-seeing eye20/400). Low vision/blindness were significantly associated with age (P.001), myopic refractive error (P.001), and level of educational background (P = .035). It was not associated with gender (P = .76) and rural vs urban area (P = .88).Blindness or low vision affects approximately one in 100 Chinese older than 40 years. An estimated 4.1 million Chinese older than 40 years have low vision, and an estimated 1.6 million Chinese older than 40 years are blind.

Purpose To evaluate intraocular pressure (IOP) and its demographic associations in an urban and rural population in Northern China. Design Population-based cohort study. Methods In the Beijing Eye Study, IOP was measured by noncontact pneumatonometry. Mean age was 56.20 ± 10.59 years (range, 40–101 years). Results Mean IOP was 16.11 ± 3.39 mm Hg (median, 16 mm Hg; range, 7–60 mm Hg). In the rural group and the urban population group, respectively, IOP was significantly ( P = .016 and P = .029, respectively) lower in the high-age group (≥75 years) than in the middle-age group (55–64 years). In the rural group, IOP was additionally significantly lower in the age group of 40 to 44 years than in the middle-age group, which suggests a reversed U-like course. A multiple regression analysis revealed that IOP significantly increased with myopia ( P = .024), and that it was statistically independent of rural area vs urban area ( P = .12) and gender ( P = .71). Conclusion In the Northern Chinese population, mean and median of IOP that is measured by pneumatonometry is 16 mm Hg with a normal range (mean ± two SDs) of 10 to 22 mm Hg. In cross-sectional analysis, IOP slightly increased towards an age of 55 to 64 years and decreased towards higher ages. IOP increased with myopia. It was not associated with rural vs urban region or gender.

To evaluate refractive error and its demographic associations in an urban and rural population in northern China.Epidemiological study.The Beijing Eye Study is a population-based cohort study in northern China including 4439 subjects. Excluding pseudophakic and aphakic patients, the present study involved 4319 subjects. It was divided into a rural part (1905 [44.1%] subjects) and an urban part (2414 [55.9%] subjects). Mean age was 55.85+/-10.33 years (range, 40-90).Standardized ophthalmologic examination. For statistical analysis, the spherical equivalent was converted to binary variables, and logistic regression was used to investigate the association with continuous or categorical independent variables.Refractive error.Mean refractive error measured -0.33+/-2.22 diopters (D) (range, -20.88 to +7.88). Myopia of-0.50 D, -1.0 D,-6.0 D, and-8 D, respectively, occurred in 22.9% (95% confidence interval [CI], 21.7-24.2), 16.9% (95% CI, 15.8-18.0), 2.6% (95% CI, 2.2-3.1), and 1.5% (95% CI, 1.1-1.9) of the subjects, respectively. Myopic refractive error was associated significantly with younger age (P0.001), urban region (vs. rural region) (P0.001), higher educational background (P0.001), higher degree of nuclear cataract (P0.001), decreasing uncorrected visual acuity (UCVA) (P0.001), decreasing best-corrected visual acuity (BCVA) (P0.001), and female gender (P0.001). Prevalence of high myopia (myopic refractive error-8 D) was associated with age (P0.001), female gender (P = 0.020), urban region (P = 0.023), and lower BCVA (P0.001). Mean anisometropia was 1.09+/-2.03 D (median, 0.38; range, 0-22.0). Prevalence of anisometropia ofor =1 D was associated significantly with age (P0.001), refractive error (P0.001), BCVA (P0.001), and region (P0.001). Mean astigmatic error measured 0.62+/-0.90 D (median, 0.25; range, 0-7.50). Astigmatism ofor =1 D was associated significantly with age (P0.001), lower UCVA (P = 0.003), lower BCVA (P0.001), urban area (P0.001), and degree of cortical cataract (P = 0.027).As in other population-based studies on Chinese, myopia was more prevalent in younger subjects. Myopia was associated with urban region, educational background, female gender, decreasing visual acuity, and nuclear cataract. If longitudinal studies confirm the association of refractive error with age, refractive surgery may achieve emmetropia only for a limited time.