GDF9His209GlnfsTer6/S428T and GDF9Q321X/S428T bi-allelic variants caused female subfertility with defective follicle enlargement.

BACKGROUND: Antral follicles consist of an oocyte cumulus complex surrounding by somatic cells, including mural granulosa cells as the inner layer and theca cells as the outsider layer. The communications between oocytes and granulosa cells have been extensively explored in in vitro studies, however, the role of oocyte-derived factor GDF9 on in vivo antral follicle development remains elusive due to lack of an appropriate animal model. Clinically, the phenotype of GDF9 variants needs to be determined. METHODS: Whole-exome sequencing (WES) was performed on two unrelated infertile women characterized by an early rise of estradiol level and defect in follicle enlargement. Besides, WES data on 1,039 women undergoing ART treatment were collected. A Gdf9Q308X/S415T mouse model was generated based on the variant found in one of the patients. RESULTS: Two probands with bi-allelic GDF9 variants (GDF9His209GlnfsTer6/S428T, GDF9Q321X/S428T) and eight GDF9S428T heterozygotes with normal ovarian response were identified. In vitro experiments confirmed that these variants caused reduction of GDF9 secretion, and/or alleviation in BMP15 binding. Gdf9Q308X/S415T mouse model was constructed, which recapitulated the phenotypes in probands with abnormal estrogen secretion and defected follicle enlargement. Further experiments in mouse model showed an earlier expression of STAR in small antral follicles and decreased proliferative capacity in large antral follicles. In addition, RNA sequencing of granulosa cells revealed the transcriptomic profiles related to defective follicle enlargement in the Gdf9Q308X/S415T group. One of the downregulated genes, P4HA2 (a collagen related gene), was found to be stimulated by GDF9 protein, which partly explained the phenotype of defective follicle enlargement. CONCLUSIONS: GDF9 bi-allelic variants contributed to the defect in antral follicle development. Oocyte itself participated in the regulation of follicle development through GDF9 paracrine effect, highlighting the essential role of oocyte-derived factors on ovarian response.

Improving Miscibility of Polymer Donor and Polymer Acceptor by Reducing Chain Entanglement for Realizing 18.64 % Efficiency All Polymer Solar Cells.

All-polymer solar cells have experienced rapid development in recent years by the emergence of polymerized small molecular acceptors (PSMAs). However, the strong chain entanglements of polymer donors (PDs) and polymer acceptors (PAs) decrease the miscibility of the resulting polymer mixtures, making it challenging to optimize the blend morphology. Herein, we designed three PAs, namely PBTPICm-BDD, PBTPICγ-BDD and PBTPICF-BDD, by smartly using a BDD unit as the polymerized unit to copolymerize with different Y-typed non-fullerene small molecular acceptors (NF-SMAs), thus achieving a certain degree of distortion and giving the polymer system enough internal space to reduce the entanglements of the polymer chains. Such effects increase the chances of the PD being interspersed into the acceptor material, which improve the solubility between the PD and PA. The PBTPICγ-BDD and PBTPICF-BDD displayed better miscibility with PBQx-TCl, leading to a well optimized morphology. As a result, high power conversion efficiencies (PCEs) of 17.50 % and 17.17 % were achieved for PBQx-TCl : PBTPICγ-BDD and PBQx-TCl : PBTPICF-BDD devices, respectively. With the addition of PYFT-o as the third component into PBQx-TCl : PBTPICγ-BDD blend to further extend the absorption spectral coverage and finely tune microstructures of the blend morphology, a remarkable PCE of 18.64 % was realized finally.

Layer-by-Layer Organic Solar Cells Enabled by 1,3,4-Selenadiazole-Containing Crystalline Small Molecule with Double-Fibril Network Morphology.

A double-fibril network of the photoactive layer morphology is recognized as an ideal structure facilitating exciton diffusion and charge carrier transport for high-performance organic solar cells (OSCs). However, in the layer-by-layer processed OSCs (LbL-OSCs), polymer donors and small molecule acceptors (SMAs) are separately deposited, and it is challenging to realize a fibril network of pure SMAs with the absence of tight interchain entanglement as polymers. In this work, crystalline small molecule donors (SMDs), named TDZ-3TR and SeDZ-3TR, were designed and introduced into the L8-BO acceptor solution, forcing the phase separation and molecular fibrilization. SeDZ-3TR showed higher crystallinity and lower miscibility with L8-BO acceptor than TDZ-3TR, enabling more driving force to favor the phase separation and better molecular fibrilization of L8-BO. On the other hand, two donor polymers of PM6 and D18 with different fibril widths and lengths were put together to optimize the fibril network of the donor layer. The simultaneously optimization of the acceptor and donor layers resulted in a more ideal double-fibril network of the photoactive layer and an impressive power conversion efficiency (PCE) of 19.38 % in LbL-OSCs.

Glycol Monomethyl Ether-Substituted Carbazolyl Hole-Transporting Material for Stable Inverted Perovskite Solar Cells with Efficiency of 25.52 .

Organic self-assembled molecules (OSAMs) based hole-transporting materials play a pivotal role in achieving highly efficient and stable inverted perovskite solar cells (IPSCs). However, the reported carbazol-based OSAMs have serious drawbacks, such as poor wettability for perovskite solution spreading due to the nonpolar surface, worse matched energy arrangement with perovskite, and limited molecular species, which greatly limit the device performance. To address above problems, a novel OSAM [4-(3,6-glycol monomethyl ether-9H-carbazol-9-yl) butyl]phosphonic acid (GM-4PACz) was synthesized as hole-transporting material by introducing glycol monomethyl ether (GM) side chains at carbazolyl unit. GM groups enhance the surface energy of Indium Tin Oxide (ITO)/SAM substrate to facilitate the nucleation and growth of up perovskite film, suppress cation defects, release the residual stress at SAM/perovskite interface, and evaluate energy level for matching with perovskite. Consequently, the GM-4PACz based IPSC achieves a champion PCE of 25.52 %, a respectable open-circuit voltage (VOC) of 1.21 V, a high stability, possessing 93.29 % and 91.75 % of their initial efficiency after aging in air for 2000 h or tracking at maximum power point for 1000 h, respectively.

20.67%-Efficiency Inorganic CsPbI3 Solar Cells Enabled by Zwitterion Ion Interface Treatment.

All-inorganic CsPbI3 perovskite solar cells (PSCs) have been extensively studied due to their high thermal stability and unprecedented rise in power conversion efficiency (PCE). Recently, the champion PCE of CsPbI3 PSCs has reached up to 21%; however, it is still much lower than that of organic-inorganic hybrid PSCs. Interface modification to passivate surface defects and minimize charge recombination and trapping is important to further improve the efficiency of CsPbI3 PSCs. Herein, a new zwitterion ion is deposited at the interface between electron transporting layer (ETL) and perovskite layer to passivate the defects therein. The zwitterion ions can not only passivate oxygen vacancy (VO ) and iodine vacancy (VI ) defects, but also improve the band alignment at the ETL-perovskite interface. After the interface treatment, the PCE of CsPbI3 device reaches up to 20.67%, which is among the highest values of CsPbI3 PSCs so far. Due to the defect passivation and hydrophobicity improvement, the PCE of optimized device remains 94% of its original value after 800 h storing under ambient condition. These results provide an efficient way to improve the quality of ETL-perovskite interface by zwitterion ions for achieving high performance inorganic CsPbI3 PSCs.

24.20%-Efficiency MA-Free Perovskite Solar Cells Enabled by Siloxane Derivative Interface Engineering.

Suppressing defects at the interface between the TiO2 electron transport layer (ETL) and perovskite film is critical for high efficiency and stable perovskite solar cells (PSCs). Herein, a siloxane derivative diethylphosphatoethylsilicic acid (PSiOH) is developed to modify the interface of TiO2 ETL/FA0.83 Cs0.17 PbI3 perovskite. Comprehensive characteristics reveal that silicon hydroxyl (SiOH) in PSiOH can reduce surface defects, improve the electrical properties and optimize the energy band structure of TiO2 by forming a SiOTi bond, while the phosphate bond (PO) in PSiOH can passivate Pb-related defects on the perovskite bottom surface. Consequently, PSiOH-modified PSCs yield a remarkable power conversation efficiency of 24.20% and improved air, thermal, or illumination stabilities. This study provides insight into passivation defects at the buried interface for efficient and stable PSCs.

Unusual Post-Translational Modifications in the Biosynthesis of Lasso Peptides.

Lasso peptides are a subclass of ribosomally synthesized and post-translationally modified peptides (RiPPs) and feature the threaded, lariat knot-like topology. The basic post-translational modifications (PTMs) of lasso peptide contain two steps, including the leader peptide removal of the ribosome-derived linear precursor peptide by an ATP-dependent cysteine protease, and the macrolactam cyclization by an ATP-dependent macrolactam synthetase. Recently, advanced bioinformatic tools combined with genome mining have paved the way to uncover a rapidly growing number of lasso peptides as well as a series of PTMs other than the general class-defining processes. Despite abundant reviews focusing on lasso peptide discoveries, structures, properties, and physiological functionalities, few summaries concerned their unique PTMs. In this review, we summarized all the unique PTMs of lasso peptides uncovered to date, shedding light on the related investigations in the future.

Wide Band-Gap Polymer Donors Functionalized with Unconventional Carbamate Side Chains for Polymer Solar Cells.

Side-chain engineering with heteroatoms is not only effective in tuning frontier molecular orbitals, but also possible for forming secondary bonds which can be utilized to planarize the molecular backbone, hence, improving the photon absorption as well as charge-transport abilities of polymer solar-cell (PSC) materials. Herein, two types of unconventional side chains, namely carboxylate and carbamate, containing various heteroatoms are introduced to the thiophene bridges in high performance benzodithiophene (BDT) based donor polymers to from the novel polymers PTzTz-C and PTzTz-N, respectively. In these polymers, non-covalent O⋅⋅⋅S and N⋅⋅⋅H interactions induce a high tendency to aggregation. In a ternary-blend PSC with PTzTz-N added to the high-performance D18 : BTP-eC9 blend, complimentary absorption and improved thin-film morphology were observed with a top power conversion efficiency of 18.76 %, which is an improvement of almost 5 % over the D18 : BTP-eC9 binary blends.

Hydrazide Derivatives for Defect Passivation in Pure CsPbI3 Perovskite Solar Cells.

All-inorganic CsPbI3 perovskite presents preeminent chemical stability and a desirable band gap as the front absorber for perovskite/silicon tandem solar cells. Unfortunately, CsPbI3 perovskite solar cells (PSCs) still show low efficiency due to high density of defects in solution-prepared CsPbI3 films. Herein, three kinds of hydrazide derivatives (benzoyl hydrazine (BH), formohydrazide (FH) and benzamide (BA)) are designed to reduce the defect density and stabilize the phase of CsPbI3 . Calculation and characterization results corroborate that the carboxyl and hydrazine groups in BH form strong chemical bonds with Pb2+ ions, resulting in synergetic double coordination. In addition, the hydrazine group in the BH also forms a hydrogen bond with iodine to assist the coordination. Consequently, a high efficiency of 20.47 % is achieved, which is the highest PCE among all pure CsPbI3 -based PSCs reported to date. In addition, an unencapsulated device showed excellent stability in ambient air.

Core clock gene Bmal1 deprivation impairs steroidogenesis in mice luteinized follicle cells.

Luteinization is the event of corpus luteum formation, a way of follicle cells transformation and a process of steroidogenesis alteration. As the core clock gene, Bmal1 was involved in the regulation of ovulation process and luteal function afterwards. Till now, the underlying roles of luteinization played by Bmal1 remain unknown. To explore the unique role of Bmal1 in luteal steroidogenesis and its underlying pathway, we investigated the luteal hormone synthesis profile in Bmal1 knockout female mice. We found that luteal hormone synthesis was notably impaired, and phosphorylation of PI3K/NfκB pathway was significantly activated. Then, the results were verified in in vitro cultured cells, including isolated Bmal1 interference granulosa cells (GCs) and theca cells (TCs), respectively. Hormones levels of supernatant culture media and mRNA expressions of steroidogenesis-associated genes (star, Hsd3ß2, cyp19a1 in GCs, Lhcgr, star, Hsd3ß2, cyp17a1 in TCs) were mutually decreased, while the phosphorylation of PI3K/NfκB was promoted during in vitro luteinization. After PI3K specific-inhibitor LY294002 intervention, mRNA expressions of Lhcgr and Hsd3ß2 were partially rescued in Bmal1 interference TCs, together with significantly increased androstenedione and T synthesis. Further exploration in TCs demonstrated BMAL1 interacted directly but negatively with NfκB p65 (RelA), a subunit which was supposed as a mediator in Bmal1-governed PI3K signaling regulation. Taken together, we verified the novel role of Bmal1 in luteal steroidogenesis, achieving by negative interplay with RelA-mediated PI3K/NfκB pathway.

No impact of treated hyperprolactinemia on cumulative live birth rate and perinatal outcomes in in vitro fertilization-embryo transfer.

AIM: To investigate whether treated hyperprolactinemia has an impact on pregnancy outcomes in in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). METHODS: A retrospective cohort study was conducted on 535 women who underwent IVF/ICSI-ET between January 2012 and December 2016, of which 123 had treated hyperprolactinemia (case group), 369 were matched controls. Besides, 43 remained hyperprolactinemic after treatment consisted of abnormal group. Cumulative live birth rate (CLBR) after one oocyte retrieval cycle was taken as the primary outcome. A time-to-event analysis using Fine and Gray's test was used to compare CLBR between case and control groups. RESULTS: The median prolactin level was 80.00 ng/mL before dopamine agonist treatment in case group, and it reduced to 14.80 ng/mL after the treatment, similar to the level of control group (15.17 ng/mL, P = 0.316). No significant differences in baseline characteristics were found between case and control groups. The CLBR after one oocyte retrieval cycle were 69.1% (85/123) and 66.4% (245/369) in the case group and control group, respectively (P = 0.580). No significant differences were found between case and control groups in perinatal outcomes. Pregnancy and perinatal outcomes of abnormal group were similar to those of case and control groups. CONCLUSION: Impact of treated hyperprolactinemia on CLBR and perinatal outcomes in IVF-ET was not evident.

Chalcogen-Atom-Annulated Perylene Diimide Trimers for Highly Efficient Nonfullerene Polymer Solar Cells.

This communication reports the synthesis of two novel chalcogen-atom-annulated perylene diimide (PDI) trimers with twisted structures, TriPDI-S and TriPDI-Se, for efficient nonfullerene polymer solar cells. TriPDI-Se exhibits more compact molecular arrangement due to the stronger intermolecular interactions induced by the selenium atom. This selenium annulation endows TriPDI-Se with improved absorption and crystallinity in its blend film. The resulting devices exhibit enhanced Jsc of 17.15 mA cm-2 and fill factor (FF) of 66.8%, which are much higher than those of TriPDI-S devices (Jsc = 16.71 mA cm-2 ; FF = 63.6%). Although TriPDI-Se exhibits lower-lying energy levels, TriPDI-Se devices still obtain a higher Voc of 0.77 V compared to TriPDI-S devices (Voc = 0.74 V), which is mainly originated from the reduced recombination in the related devices. Finally, the power conversion efficiency is significantly elevated from 7.86% for TriPDI-S devices to 8.82% for TriPDI-Se devices.

Influence of brewing conditions on taste components in Fuding white tea infusions.

BACKGROUND: White tea has received increasing attention of late as a result of its sweet taste and health benefits. During the brewing of white tea, many factors may affect the nutritional and sensory quality of the resulting infusions. The present study aimed to investigate the effect of various infusion conditions on the taste components of Fuding white tea, including infusion time, ratio of tea and water, number of brewing steps, and temperature. RESULTS: Brewing conditions had a strong effect on the taste compound profile and sensory characteristics. The catechin, caffeine, theanine and free amino acid contents generally increased with increasing infusion time and temperature. Conditions comprising an infusion time of 7 min, a brewing temperature of 100 °C, a tea and water ratio of 1:30 or 1:40, and a second brewing step, respectively, were shown to obtain the highest contents of most compounds. Regarding tea sensory evaluation, conditions comprising an infusion time of 3 min, a brewing temperature of 100 °C, a tea and water ratio of 1:50, and a first brewing step, resulted in the highest sensory score for comprehensive behavior of color, aroma and taste. CONCLUSION: The results of the present study reveal differences in the contents of various taste compounds, including catechins, caffeine, theanine and free amino acids, with respect to different brewing conditions, and sensory scores also varied with brewing conditions. © 2016 Society of Chemical Industry.

Effect of water quality on the main components in Fuding white tea infusions.

The aim of this study was to investigate the effect of water quality on the main components in Fuding white tea infusions, including catechins, caffeine, theanine and free amino acids. Pure, tap and spring water were tested, and water quality was found to have a distinct effect on the main compounds extracted. Pure water, which was weakly acidic and low in dissolved ions, achieved the highest catechin content, whereas caffeine and theanine, and amino acids, were higher in infusions made with spring and tap water, respectively. Sensory evaluation was performed to evaluate infusion colour, taste and aroma, and sensory quality was similarly influenced by water type, due primarily to differences in dissolved ions. Pure water was more suitable for brewing white tea with superior colour, aroma and taste.

18.6% Efficiency All-Polymer Solar Cells Enabled by a Wide Bandgap Polymer Donor Based on Benzo[1,2-d:4,5-d']bisthiazole.

The limited selection of wide bandgap polymer donors for all-polymer solar cells (all-PSCs) is a bottleneck problem restricting their further development and remains poorly studied. Herein, a new wide bandgap polymer, namely PBBTz-Cl, is designed and synthesized by bridging the benzobisthiazole acceptor block and chlorinated benzodithiophene donor block with thiophene units for application as an electron donor in all-PSCs. PBBTz-Cl not only possesses wide bandgap and deep energy levels but also displays strong absorption, high-planar structure, and good crystallinity, making it a promising candidate for application as a polymer donor in organic solar cells. When paired with the narrow bandgap polymer acceptor PY-IT, a fibril-like morphology forms, which facilitates exciton dissociation and charge transport, contributing to a power conversion efficiency (PCE) of 17.15% of the corresponding all-PSCs. Moreover, when introducing another crystalline polymer acceptor BTP-2T2F into the PBBTz-Cl:PY-IT host blend, the absorption ditch in the range of 600-750 nm is filled, and the blend morphology is further optimized with the trap density reducing. As a result, the ternary blend all-PSCs achieve a significantly improved PCE of 18.60%, which is among the highest values for all-PSCs to date.

Crossbreeding Effect of Chalcogenation and Iodination on Benzene Additives Enables Optimized Morphology and 19.68% Efficiency of Organic Solar Cells.

Volatile solid additives have attracted increasing attention in optimizing the morphology and improving the performance of currently dominated non-fullerene acceptor-based organic solar cells (OSCs). However, the underlying principles governing the rational design of volatile solid additives remain elusive. Herein, a series of efficient volatile solid additives are successfully developed by the crossbreeding effect of chalcogenation and iodination for optimizing the morphology and improving the photovoltaic performances of OSCs. Five benzene derivatives of 1,4-dimethoxybenzene (DOB), 1-iodo-4-methoxybenzene (OIB), 1-iodo-4-methylthiobenzene (SIB), 1,4-dimethylthiobenzene (DSB) and 1,4-diiodobenzene (DIB) are systematically studied, where the widely used DIB is used as the reference. The effect of chalcogenation and iodination on the overall property is comprehensively investigated, which indicates that the versatile functional groups provided various types of noncovalent interactions with the host materials for modulating the morphology. Among them, SIB with the combination of sulphuration and iodination enabled more appropriate interactions with the host blend, giving rise to a highly ordered molecular packing and more favorable morphology. As a result, the binary OSCs based on PM6:L8-BO and PBTz-F:L8-BO as well as the ternary OSCs based on PBTz-F:PM6:L8-BO achieved impressive high PCEs of 18.87%, 18.81% and 19.68%, respectively, which are among the highest values for OSCs.

19.32% Efficiency Polymer Solar Cells Enabled by Fine-Tuning Stacking Modes of Y-Type Molecule Acceptors: Synergistic Bromine and Fluorine Substitution of the End Groups.

The success of Y6-type nonfullerene small molecule acceptors (NF-SMAs) in polymer solar cells (PSCs) can be attributed to their unique honeycomb stacking style, which leads to favorable thin-film morphologies. The intermolecular interactions related to the crystallization tendency of these NF-SMAs is closely governed by their electron accepting end groups. For example, the high performance Y6 derivative L8-BO (BTP-4F) presents three types of stacking modes in contrast to two stacking modes of Y6. Hence, it is ultimately interesting to obtain more insight on the packing properties and the preferences influenced by chemical modifications such as end group engineering. This work designs and synthesizes asymmetric and symmetric L8-BO derivatives with brominated end groups and explores the stacking preferences in various modes. The asymmetric BTP-3FBr displays an optimized crystallization tendency and thin film morphology, leading to a decent power conversion efficiency (PCE) of 18.34% in binary devices and a top PCE of 19.32% in ternary devices containing 15 wt% IDIC as the second acceptor.

In Situ Synthesized Low-Dimensional Perovskite for >25% Efficiency Stable MA-Free Perovskite Solar Cells.

Developing an additive to effectively regulate the perovskite crystallization kinetics for the optimized optoelectronic properties of perovskite film plays a vital role in obtaining high efficiency and stable perovskite solar cells (PSCs). Herein, a new additive is designed and directly synthesized in perovskite precursor solution by utilizing an addition reaction between but-3-yn-1-amine hydrochloride (BAH) and formamidinium iodide. It is found that its product may control the intermediate precursor phase for regulating perovskite nucleation, leading to advantageous 2D perovskite to induce growth of perovskite along the preferred [001] orientation with not only released lattice strain but also strong interaction with perovskite to passivate its surface defects. By taking advantage of the above synergistic effects, the optimized PSC delivers an efficiency of 25.19% and a high open-circuit voltage (VOC) of 1.22 V. Additionally, the devices demonstrate good stability, remaining over 90% of their initial efficiencies under ambient atmosphere conditions for 60 days, high temperature of 85 °C for 200 h, or maximum power point tracking for 500 h.

Bioinformatics Analysis Identifies Key Genes in Recurrent Implantation Failure Based on Immune Infiltration.

Recurrent implantation failure (RIF) is a thorny problem often encountered in the field of assisted reproduction. Existing evidences suggest that immune dysregulation may be involved in the pathogenesis of RIF. The purpose of this study is to explore immune-related genes contributing to RIF through data mining. The endometrial expression profiles of 24 RIF and 24 controls were obtained from the GEO database. The immune infiltration in bulk tissue was estimated by single sample gene set enrichment analysis (ssGSEA) method based on marker gene sets for immune cells generated from endometrial single-cell RNA sequencing data. The results showed that the infiltration levels of B cells and regulatory T cells (Tregs) were significantly reduced in the RIF group. Four hub genes (GJA1, PRKAG2, CPT1A, and ICA1) were identified by integrated analysis of weighted gene co-expression network analysis (WGCNA), random forest and LASSO regression. Moreover, these hub genes were significantly correlated with certain immune-related factors, especially CXCL12, CEACAM1, and XCR1. Single-gene GSEA indicated that the pathways associated with hub genes included the regulation of cell cycle, the process of epithelial-mesenchymal transition and transplant rejection, etc. A predictive model for RIF was constructed based on hub genes and performed well in the training dataset and the other two external datasets. Thus, this study identified immune-related key genes in RIF and provided new biomarkers for early diagnosis.

Y-Type Non-Fullerene Acceptors with Outer Branched Side Chains and Inner Cyclohexane Side Chains for 19.36% Efficiency Polymer Solar Cells.

Raising the lowest unoccupied molecular orbital (LUMO) energy level of Y-type non-fullerene acceptors can increase the open-circuit voltage (Voc ) and thus the photovoltaic performance of the current top performing polymer solar cells (PSCs). One of the viable routes is demonstrated by the successful Y6 derivative of L8-BO with the branched alkyl chains at the outer side. This will introduce steric hindrance and reduce intermolecular aggregation, thus open up the bandgap and raise the LUMO energy level. To take further advantages of the steric hindrance influence on optoelectronic properties of Y6 derivatives, two Y-type non-fullerene acceptors of BTP-Cy-4F and BTP-Cy-4Cl are designed and synthesized by adopting outer branched side chains and inner cyclohexane side chains. An outstanding Voc of 0.937 V is achieved in the D18:BTP-Cy-4F binary blend devices along with a power conversion efficiency (PCE) of 18.52%. With the addition of BTP-eC9 to extend the absorption spectral coverage, a remarkable PCE of 19.36% is realized finally in the related ternary blend devices, which is one of the highest values for single-junction PSCs at present. The results illustrate the great potential of cyclohexane side chains in constructing high-performance non-fullerene acceptors and their PSCs.