MCM8 interacts with DDX5 to promote R-loop resolution.

MCM8 has emerged as a core gene in reproductive aging and is crucial for meiotic homologous recombination repair. It also safeguards genome stability by coordinating the replication stress response during mitosis, but its function in mitotic germ cells remains elusive. Here we found that disabling MCM8 in mice resulted in proliferation defects of primordial germ cells (PGCs) and ultimately impaired fertility. We further demonstrated that MCM8 interacted with two known helicases DDX5 and DHX9, and loss of MCM8 led to R-loop accumulation by reducing the retention of these helicases at R-loops, thus inducing genome instability. Cells expressing premature ovarian insufficiency-causative mutants of MCM8 with decreased interaction with DDX5 displayed increased R-loop levels. These results show MCM8 interacts with R-loop-resolving factors to prevent R-loop-induced DNA damage, which may contribute to the maintenance of genome integrity of PGCs and reproductive reserve establishment. Our findings thus reveal an essential role for MCM8 in PGC development and improve our understanding of reproductive aging caused by genome instability in mitotic germ cells.

FAAP100 is required for the resolution of transcription-replication conflicts in primordial germ cells.

BACKGROUND: The maintenance of genome stability in primordial germ cells (PGCs) is crucial for the faithful transmission of genetic information and the establishment of reproductive reserve. Numerous studies in recent decades have linked the Fanconi anemia (FA) pathway with fertility, particularly PGC development. However, the role of FAAP100, an essential component of the FA core complex, in germ cell development is unexplored. RESULTS: We find that FAAP100 plays an essential role in R-loop resolution and replication fork protection to counteract transcription-replication conflicts (TRCs) during mouse PGC proliferation. FAAP100 deletion leads to FA pathway inactivation, increases TRCs as well as cotranscriptional R-loops, and contributes to the collapse of replication forks and the generation of DNA damage. Then, the activated p53 signaling pathway triggers PGC proliferation defects, ultimately resulting in insufficient establishment of reproductive reserve in both sexes of mice. CONCLUSIONS: Our findings suggest that FAAP100 is required for the resolution of TRCs in PGCs to safeguard their genome stability.

UBE2T resolves transcription-replication conflicts and protects common fragile sites in primordial germ cells.

The proper development of primordial germ cells (PGCs) is an essential prerequisite for gametogenesis and mammalian fertility. The Fanconi anemia (FA) pathway functions in maintaining the development of PGCs. FANCT/UBE2T serves as an E2 ubiquitin-conjugating enzyme that ubiquitylates the FANCD2-FANCI complex to activate the FA pathway, but its role in the development of PGCs is not clear. In this study, we found that Ube2t knockout mice showed defects in PGC proliferation, leading to severe loss of germ cells after birth. Deletion of UBE2T exacerbated DNA damage and triggered the activation of the p53 pathway. We further demonstrated that UBE2T counteracted transcription-replication conflicts by resolving R-loops and stabilizing replication forks, and also protected common fragile sites by resolving R-loops in large genes and promoting mitotic DNA synthesis to maintain the genome stability of PGCs. Overall, these results provide new insights into the function and regulatory mechanisms of the FA pathway ensuring normal development of PGCs.

DNA repair protein FANCD2 has both ubiquitination-dependent and ubiquitination-independent functions during germ cell development.

When DNA interstrand crosslink lesions occur, a core complex of Fanconi anemia proteins promotes the ubiquitination of FANCD2 and FANCI, which recruit downstream factors to repair the lesion. However, FANCD2 maintains genome stability not only through its ubiquitination-dependent but also its ubiquitination-independent functions in various DNA damage response pathways. Increasing evidence suggests that FANCD2 is essential for fertility, but its ubiquitination-dependent and ubiquitination-independent roles during germ cell development are not well characterized. In this study, we analyzed germ cell development in Fancd2 KO and ubiquitination-deficient mutant (Fancd2K559R/K559R) mice. We showed that in the embryonic stage, both the ubiquitination-dependent and ubiquitination-independent functions of FANCD2 were required for the expansion of primordial germ cells and establishment of the reproductive reserve by reducing transcription-replication conflicts and thus maintaining genome stability in primordial germ cells. Furthermore, we found that during meiosis in spermatogenesis, FANCD2 promoted chromosome synapsis and regulated crossover formation independently of its ubiquitination, but that both ubiquitinated and nonubiquitinated FANCD2 functioned in programmed double strand break repair. Finally, we revealed that on meiotic XY chromosomes, H3K4me2 accumulation required ubiquitination-independent functionality of FANCD2, while the regulation of H3K9me2 and H3K9me3 depended on FANCD2 ubiquitination. Taken together, our findings suggest that FANCD2 has distinct functions that are both dependent on and independent of its ubiquitination during germ cell development.

Transcription-replication conflicts in primordial germ cells necessitate the Fanconi anemia pathway to safeguard genome stability.

Preserving a high degree of genome integrity and stability in germ cells is of utmost importance for reproduction and species propagation. However, the regulatory mechanisms of maintaining genome stability in the developing primordial germ cells (PGCs), in which rapid proliferation is coupled with global hypertranscription, remain largely unknown. Here, we find that mouse PGCs encounter a constitutively high frequency of transcription-replication conflicts (TRCs), which lead to R-loop accumulation and impose endogenous replication stress on PGCs. We further demonstrate that the Fanconi anemia (FA) pathway is activated by TRCs and has a central role in the coordination between replication and transcription in the rapidly proliferating PGCs, as disabling the FA pathway leads to TRC and R-loop accumulation, replication fork destabilization, increased DNA damage, dramatic loss of mitotically dividing mouse PGCs, and consequent sterility of both sexes. Overall, our findings uncover the unique source and resolving mechanism of endogenous replication stress during PGC proliferation, provide a biological explanation for reproductive defects in individuals with FA, and improve our understanding of the monitoring strategies for genome stability during germ cell development.

Predictive Design Model for Low-Dimensional Organic-Inorganic Halide Perovskites Assisted by Machine Learning.

Low-dimensional organic-inorganic halide perovskites have attracted interest for their properties in exciton dynamics, broad-band emission, magnetic spin selectivity. However, there is no quantitative model for predicting the structure-directing effect of organic cations on the dimensionality of these low-dimensional perovskites. Here, we report a machine learning (ML)-assisted approach to predict the dimensionality of lead iodide-based perovskites. A literature review reveals 86 reported amines that are classified into "2D"-forming and "non-2D"-forming based on the dimensionality of their perovskites. Machining learning models were trained and tested based on the classification and descriptor features of these ammonium cations. Four structural features, including steric effect index, eccentricity, largest ring size, and hydrogen-bond donor, have been identified as the key controlling factors. On the basis of these features, a quantified equation is created to calculate the probability of forming 2D perovskite for a selected amine. To further illustrate its predicting capability, the built model is applied to several untested amines, and the predicted dimensionality is verified by growing single crystals of perovskites from these amines. This work represents a step toward predicting the crystal structures of low dimensional hybrid halide perovskites using ML as a tool.

Dye-sensitized photocathodes for oxygen reduction: efficient H2O2 production and aprotic redox reactions.

Dye-sensitized photoelectrochemical cells (DSPECs) can be used to store solar energy in the form of chemical bonds. Hydrogen peroxide (H2O2) is a versatile energy carrier and can be produced by reduction of O2 on a dye-sensitized photocathode, in which the design of dye molecules is crucial for the conversion efficiency and electrode stability. Herein, using a hydrophobic donor-double-acceptor dye (denoted as BH4) sensitized NiO photocathode, hydrogen peroxide (H2O2) can be produced efficiently by reducing O2 with current density up to 600 µA cm-2 under 1 sun conditions (Xe lamp as sunlight simulator, λ > 400 nm). The DSPECs maintain currents greater than 200 µA cm-2 at low overpotential (0.42 V vs. RHE) for 18 h with no decrease in the rate of H2O2 production in aqueous electrolyte. Moreover, the BH4 sensitized NiO photocathode was for the first time applied in an aprotic electrolyte for oxygen reduction. In the absence of a proton source, the one-electron reduction of O2 generates stable, nucleophilic superoxide radicals that can then be synthetically utilized in the attack of an available electrophile, such as benzoyl chloride. The corresponding photocurrent generated by this photoelectrosynthesis is up to 1.8 mA cm-2. Transient absorption spectroscopy also proves that there is an effective electron transfer from reduced BH4 to O2 with a rate constant of 1.8 × 106 s-1. This work exhibits superior photocurrent in both aqueous and non-aqueous systems and reveals the oxygen/superoxide redox mediator mechanism in the aprotic chemical synthesis.

Excimer-Mediated Intermolecular Charge Transfer in Self-Assembled Donor-Acceptor Dyes on Metal Oxides.

When conjugate molecules are self-assembled on the surface of semiconductors, emergent properties resulting from the electronic coupling between the conjugate moieties are of importance in the interfacial electron-transfer dynamics for photoelectrochemical and optoelectronics devices. In this work, we investigate the self-assembly of triphenylamine-oligothiophene-perylenemonoimide (PMI) molecules, denoted as BH4, on metal oxide surfaces via UV-vis absorption, photoluminescence, and transient near-infrared absorption spectroscopies and molecular dynamics simulations, and we report the excimer formation due to the π-π interaction of the PMI units between the neighboring dye molecules. To our best knowledge, this is the first experimental observation of intermolecular excimer formation when conjugate donor-acceptor molecules form a self-assembled monolayer. In addition, a long-lived (4.3 µs) intermolecular charge separation is observed, and a new excimer-mediated intermolecular charger-transfer mechanism is proposed. This work demonstrates that, through the design of dye molecules, the excited complexes or aggregates can provide a pathway to slow down the recombination rate in photoelectrodes that utilize donor-acceptor dyad molecules.

Novel FSHR mutations in Han Chinese women with sporadic premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is characterized by amenorrhea and elevated levels of follicle-stimulating hormone (FSH, usually > 25 IU/L) before 40 years of age. To identify the relationship between FSHR mutations and sporadic POI patients of Han Chinese descent, we performed Sanger sequencing of FSHR gene in 192 sporadic POI patients and 192 matched controls of Han Chinese descent. Two heterozygous missense variants, c.793A > G (p.M265V) and c.1789C > A (p.L597I), were identified exclusively in POI patients. Functional studies showed that both mutants were expressed on the cell surface, while p.L597I showed decreased membrane localization compared with wild-type FSHR. Moreover, FSH-induced cAMP production and ERK1/2 phosphorylation were reduced in the cells transfected with p.L597I mutant, but not in the cells transfected with p.M265V mutant. In addition, two single-nucleotide polymorphisms (SNPs), rs1394205 (c.-29G > A) and rs140106399 (c.*111 T > C), were identified in both POI group and control group with significantly different genotypic and allelic distributions. These results indicated that dysfunctional FSHR due to mutation or SNPs might explain a fraction of sporadic POI cases in Han Chinese population.

Effects of the terms and characteristics of cadres on environmental pollution: Evidence from 230 cities in China.

This study investigates the effects of cadres' terms and characteristics on environmental pollution by collecting data of 230 prefecture-level cities in 2002-2014. Results show that (1) the cadres' term shows an "inverted U" effect on environmental pollution, or it shows "first deterioration and later improvement" effect on environment. (2) Highly educated cadres are aware of the importance of environmental protection for sustainable economic development and have negative effects on environmental pollution; also, the aged cadres are less likely to be promoted and thus help to environmental protection. (3) The party congress will cause the cadres to focus on economic growth, thus ignoring environmental protection. (4) The effects of cadres on environmental pollution vary across different regions; the effects in central and western China are more serious than that in eastern China. It enriches the evidence on the relationship between governance and environmental pollution, which is significant to the government's formulation and implementation of policies related to environment protection.

A strategy for fabrication of controllable 3D pattern containing clusters and nanoparticles inside a solid material.

Directly controlling the growth process of clusters and nanoparticles is an effective way to tune their specific properties, which has been considered as a significant issue lying at the heart of nanotechnology. For technological applications, great strides have been made in the assembly of clusters and nanoparticles. However, controllable synthesis of clusters and nanoparticles inside a bulk solid-state medium remains a tremendous challenge, which is important for integrated devices. Here we report a strategy for space-selective control of elemental tellurium (Te) precipitation as clusters or nanoparticles in glass by femtosecond (fs) laser irradiation. After irradiation by a 1 kHz fs laser at 800 nm, Te2 clusters, which emit near-infrared (NIR) light, are observed at the focal point of the laser beam inside the glass sample. By shifting the repetition rate to 250 kHz, a temperature field forms around the focal area that facilitates transformation of Te clusters into nanoparticles. Raman mapping shows that the clusters are localized in the center of the laser-induced microstructure, while the nanoparticles exhibit an annular distribution. The possible mechanisms of generation and distribution of different species are discussed. We have also demonstrated optical data storage and embedded micro-grating by using this technique.

Fabrication of microchannels by space-selective control of phase separation in glass.

Microchannels have important scientific applications in many fields, because they enable precise control, manipulation, and analysis of fluid on a micrometer scale. Herein, we demonstrate an effective strategy for fabrication of microchannels, based on the space-selective phase separation in glass induced by a femtosecond laser. The proposed method shows its abilities in fabrication of three-dimensional microchannels with ∼5 mm length scale and a uniform cross section. Moreover, we also achieve the modulation of the morphology on the inner surface of microchannels by using objective lenses with various numerical-apertures. The physical mechanism of the phase separation and microstructure evolution is discussed. Our method provides new opportunities to fabricate microchannels with complex structures and multifunctional integration.

MoS2 nanoflowers as high performance saturable absorbers for an all-fiber passively Q-switched erbium-doped fiber laser.

Strong saturable absorption was observed in MoS2 nanoflowers, which were synthesized by a facile solvothermal method. A MoS2 nanoflower-based saturable absorber with a high modulation depth of 51.8% and a large saturable intensity of 275.5 GW cm(-2) was introduced to the application of passively Q-switched fiber laser generation. Stable passively Q-switched fiber laser pulses at 1.56 µm with a low threshold power of 16.10 mW, high signal-to-noise ratio of 52.5 dB and short pulse duration of 1.9 µs were obtained. More importantly, a high output power of 3.10 mW related to a large pulse energy of about 51.84 nJ can be attained at a very low pump power. The efficiency of the laser reaches 4.71%, which is larger than that of the prepared layered MoS2 and recently reported MoS2-based passively Q-switching operations. Such results imply that the MoS2 nanoflowers are an excellent candidate for a saturable absorber in passively Q-switched fiber lasers at a low pump intensity.

Topological engineering of glass for modulating chemical state of dopants.

A novel approach to modulating the chemical state of dopants by engineering the topological features of a glass matrix is presented. The method allows selective stabilization of dopants on a wide range of length scales, from dispersed ions to aggregated clusters to nanoparticles, leading to various intriguing optical phenomena, such as great emission enhancement and ultra-broadband optical amplification.

Grating-assisted generation of regular two-dimensional multicolored arrays in a tellurite glass.

A grating structure was inscribed in a tellurite glass after irradiation with high-repetition rate femtosecond laser pulses. High diffraction efficiency was obtained due to the large refractive index change, which was caused by the precipitation of Te crystals in the laser modified region. Two-dimensional multicolored arrays were generated by cascaded four-wave mixing (CFWM) together with the prefabricated grating structure, which showed much more superior than those induced by beam breakup.

Space-selective precipitation of ZnO crystals in glass by using high repetition rate femtosecond laser irradiation.

We report on three-dimensional (3D) precipitation of ZnO crystals inside a silicate glass by a 500 kHz femtosecond pulse laser. The precipitation and distribution of ZnO crystals in glass are confirmed and analyzed by Raman spectra and Raman mapping. Mirco- luminescence is observed in the laser modified region when excited by femtosecond pulse laser or Xenon lamp. The effect of laser average power on the precipitation of the ZnO crystals has also been investigated. The possibility of 3D optical data storage using the observed phenomena is demonstrated.

Origin of structural relaxation dependent spectroscopic features of bismuth-activated glasses.

For the first time, we studied the effect of structural relaxation on the NIR spectroscopic properties of bismuth-activated germanium glasses below glass transition temperature. Interestingly, distinct change behavior of NIR luminescence is observed at two different heat-treatment temperature ranges corresponding to two different relaxation behavior of glass structure. Besides, when structural modified by partly substituting B(2)O(3) for GeO(2), a narrower and more thermal sensitive luminescence is observed, which is inexplicable by "inhomogeneous broadening" and we tentatively attribute it to a defect-involved reason. Fundamentally the results here not only provide us a deeper insight into the optical property of bismuth-activated materials but also increase our understanding of the glassy state, and practically it delivers some valuable guidance in designing bismuth-activated glasses with superior NIR optical properties.

Fabrication of polarization-dependent light attenuator in fused silica using a low-repetition-rate femtosecond laser.

In this Letter, we have demonstrated the direct writing of polarization-dependent light attenuator inside fused silica by tailoring 1 kHz femtosecond (fs) laser induced self-organized nanogratings. Optical birefringence was observed to vary with the polarization plane azimuth of the fs laser and scanning direction. The formation of self-organized nanogratings was confirmed by scanning electron microscopy observation. A polarization-dependent light attenuator was fabricated by forming a plane consisting of nanograting lines inside fused silica by scanning the fs laser. The attenuation efficiency was improved by forming a multilayer nanograting structure. The technique may find important applications in micro-optical devices.