The Transcriptome and DNA Methylome Landscapes of Human Primordial Germ Cells.

Germ cells are vital for transmitting genetic information from one generation to the next and for maintaining the continuation of species. Here, we analyze the transcriptome of human primordial germ cells (PGCs) from the migrating stage to the gonadal stage at single-cell and single-base resolutions. Human PGCs show unique transcription patterns involving the simultaneous expression of both pluripotency genes and germline-specific genes, with a subset of them displaying developmental-stage-specific features. Furthermore, we analyze the DNA methylome of human PGCs and find global demethylation of their genomes. Approximately 10 to 11 weeks after gestation, the PGCs are nearly devoid of any DNA methylation, with only 7.8% and 6.0% of the median methylation levels in male and female PGCs, respectively. Our work paves the way toward deciphering the complex epigenetic reprogramming of the germline with the aim of restoring totipotency in fertilized oocytes.

Triglyceride glucose-body mass index as a novel predictor of slow coronary flow phenomenon in patients with ischemia and nonobstructive coronary arteries (INOCA).

BACKGROUND: The triglyceride glucose-body mass index (TyG-BMI index) has been suggested as a novel predictor of insulin resistance. However, its predictive value for slow coronary flow phenomenon (SCFP) in patients with ischemia and nonobstructive coronary arteries (INOCA) remains unclear. METHODS: We consecutively recruited 1625 patients with INOCA from February 2019 to February 2023 and divided them into two groups based on thrombolysis in myocardial infarction (TIMI) frame counts (TFCs): the SCFP group (n = 79) and the control group. A 1:2 age-matched case-control study was then performed. The TyG-BMI index was calculated as ln [plasma triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. RESULTS: TyG-BMI index in the SCFP group (218.3 ± 25.2 vs 201.0 ± 26.5, P < .001) was significantly higher than in the normal controls. TyG-BMI index also increased with the number of coronary arteries involved in the SCFP. Multivariate logistic regression analysis showed that TyG-BMI, BMI, and TG were independent predictors for SCFP. Receiver operating characteristic (ROC) curve analysis showed that when the TyG-BMI index was above 206.7, the sensitivity and specificity were 88.6% and 68.5%, respectively, with an AUC of 0.809 (95% CI: 0.756-0.863, P = .027). Combined BMI with TG, the TyG-BMI index had a better predictive value for SCFP than BMI and TG (P < .001). CONCLUSION: The TyG-BMI index was an independent predictor for SCFP in INOCA patients, and it had a better predictive value than BMI and TG.

Unusual Thermal Quenching of Photoluminescence from an Organic-Inorganic Hybrid [MnBr4 ]2- -based Halide Mediated by Crystalline-Crystalline Phase Transition.

The ability to generate and manipulate photoluminescence (PL) behavior has been of primary importance for applications in information security. Excavating novel optical effects to create more possibilities for information encoding has become a continuous challenge. Herein, we present an unprecedented PL temporary quenching that highly couples with thermodynamic phase transition in a hybrid crystal (DMML)2 MnBr4 (DMML=N,N-dimethylmorpholinium). Such unusual PL behavior originates from the anomalous variation of [MnBr4 ]2- tetrahedrons that leads to non-radiation recombination near the phase transition temperature of 340 K. Remarkably, the suitable detectable temperature, narrow response window, high sensitivity, and good cyclability of this PL temporary quenching will endow encryption applications with high concealment, operational flexibility, durability, and commercial popularization. Profited from these attributes, a fire-new optical encryption model is devised to demonstrate high confidential information security. This unprecedented optical effect would provide new insights and paradigms for the development of luminescent materials to enlighten future information encryption.

Organic-Inorganic Hybrid Ferroelectric and Antiferroelectric with Afterglow Emission.

Luminescent ferroelectrics are holding exciting prospect for integrated photoelectronic devices due to potential light-polarization interactions at electron scale. Integrating ferroelectricity and long-lived afterglow emission in a single material would offer new possibilities for fundamental research and applications, however, related reports have been a blank to date. For the first time, we here achieved the combination of notable ferroelectricity and afterglow emission in an organic-inorganic hybrid material. Remarkably, the presented (4-methylpiperidium)CdCl3 also shows noticeable antiferroelectric behavior. The implementation of cationic customization and halogen engineering not only enables a dramatic enhancement of Curie temperature of 114.4 K but also brings a record longest emission lifetime up to 117.11 ms under ambient conditions, realizing a leapfrog improvement of at least two orders of magnitude compared to reported hybrid ferroelectrics so far. This finding would herald the emergence of novel application potential, such as multi-level density data storage or multifunctional sensors, towards the future integrated optoelectronic devices with multitasking capabilities.

Introducing Ferroelasticity into 1D Hybrid Lead Halide Semiconductor by Halogen Substitution Strategy.

Organic-inorganic hybrid lead halide perovskites (OLHPs), represented by (CH3 NH3 )PbI3 , are one of the research focus due to their exceptional performance in optoelectronic applications, and ferroelastic domain walls are benign to their charge carrier transport that is confirmed recently. Among them, the 1D OLHPs feature better stability against desorption and moisture, but related 1D ones possessing ferroelasticity are rarely investigated and reported so far. In this work, the 1D ferroelastic semiconductor (N-iodomethyl-N-methyl-morpholinium)PbI3 ((IDMML)PbI3 ) is prepared successfully by introducing successively halogenate atoms from Cl, Br to I into the organic cation of the prototype (N,N-dimethylmorpholinium)PbI3 ((DMML)PbI3 ). Notably, (IDMML)PbI3 shows the narrow bandgap energy (≈2.34 eV) according to the ultraviolet-visible absorption spectrum and the theoretical calculation, and possesses the evident photoconductive characteristic with the on/off ratio of current of ≈50 under the 405 nm light irradiation. This work provides a new case for the ferroelastic OLHPs and will inspire intriguing research in the field of optoelectronic.

Application of the PGT-M strategy using single sperm and/or affected embryos as probands for linkage analysis in males with hereditary tumor syndromes without family history.

Hereditary tumor syndromes have garnered substantial attention due to their adverse effects on both the physical and psychological health of patients, as well as the elevated risk of transmission to subsequent generations. This has prompted a growing interest in exploring preimplantation genetic testing (PGT) as a treatment option to mitigate and eliminate these impacts. Several studies have demonstrated that de novo variants have become a great cause of many hereditary tumor syndromes, which introduce certain difficulties to PGT. In the absence of adequate genetic linkage information (parents and offspring), haplotype construction seems unrealizable. In the study, researchers used single sperm or affected embryos as proband to perform single-nucleotide polymorphism linkage analysis for cases with de novo variants. For complicated variants, the strategy that sperm combined with embryo detection will increase accuracy while avoiding the limitations and potential failures of using a single detection material. The study recruited 11 couples with male de novo carriers, including 3 tumor types and 4 genes. To date, 4 couples have been clinically confirmed as pregnant and three healthy babies have been born. The results of amniocentesis or umbilical cord blood verification were consistent with the results of PGT-M. The study aims to introduce the application of the PGT-M strategy in hereditary tumor syndromes.

Homochiral Chemistry Strategy to Trigger Second-Harmonic Generation and Dual Dielectric Switches.

Switchable materials have attracted enormous interest due to their promising applications in important fields such as sensing, electronic components, and information storage. Nevertheless, obtaining multifunctional switching materials is still a problem worth investigating. Herein, by incorporating (Rac-, L-, D-2-amino-1-propanol) as the templating cation, we have obtained (Rac-, L-, D-HTMPA)CdCl3 (HTMPA = 1-hydroxy-N, N, N-trimethyl-2-propanaminium). We have adopted a chiral chemistry strategy that causes (Rac-HTMPA)CdCl3 in the central symmetric space to crystallize in the chiral space group. Based on the modulation of the homochiral strategy, (L-, D-HTMPA)CdCl3 shows a dual phasic transition at 269 and 326 K and a switchable second-harmonic generation response. In addition, (L-, D-HTMPA)CdCl3 is chiral switchable material to exhibit stable dual dielectric and second-harmonic generation (SHG) switches. This work provides an approach to exploring multifunctional chiral switchable materials.

"Liu-Liang-Chung" syndrome with multiple congenital anomalies and the distinctive craniofacial features caused by dominant ZEB2 gene gain mutation.

BACKGROUND: Contiguous gene gain syndrome including entire ZEB2 may be a novel syndrome. In the past, there were no easily distinct and recognizable features as a guide for precise clinical and genetic diagnosis of the syndrome. CASE PRESENTATION: We report a novel case with the syndrome with a novel de novo 22.16 Mb duplication at 2q21.2-q24.1. The syndrome is characterized by multiple anomalies including the same typical craniofacial phenotype that is entirely different from Mowat-Wilson syndrome (MWS), and other quite similar features of MWS consisting of development delay, congenital heart disease, abdominal abnormalities, urogenital abnormalities, behavioral problems and so on, in which the distinctive craniofacial features can be more easily recognized. CONCLUSIONS: Contiguous gene gain syndrome including entire ZEB2 characterized with similar multiple congenital anomalies of MWS and the distinctive craniofacial features is mainly caused by large 2q22 repeats including ZEB2 leading to dominant singe ZEB2 gene gain mutation, which is recommended to be named "Liu-Liang-Chung" syndrome. We diagnose this novel syndrome to distinguish it from MWS. Some variable additional features in the syndrome including remarkable growth and development retardation and protruding ears were recognized for the first time.

Electrochemical chiral sensor for levofloxacin detection base on Cu/Fe-BTC amplification.

The key to developing sensors for chiral drug determination is to exclude interference from enantiomers. In this study, metal-organic frameworks (MOFs) and molecularly imprinted polymer (MIP) were introduced to prepare a chiral sensor for levofloxacin detection. The MIP was electropolymerised on the surface of the Cu/Fe-benzene-1,3,5-tricarboxylate MOF (Cu/Fe-BTC)-modified Au electrode using levofloxacin as a template molecule. After eluting the levofloxacin, a chiral sensor with recognition sites for levofloxacin was obtained. With this site as a switch, a novel method for detecting levofloxacin was established. Because of the enhanced recognition effect, the sensor can effectively exclude the enantiomeric interference of d-ofloxacin. Moreover, Cu/Fe-BTC can effectively amplify the current response signal and improve the sensitivity of the sensor. The linear range of the sensor was 5 to 4000 × 10-11 mol L-1, and the detection limit was 2.07 × 10-11 mol L-1. When applied to detecting levofloxacin in actual samples, the sensor showed a 92.7-109.8% recovery.

Molecular Engineering of Corrole Radicals by Polycyclic Aromatic Fusion: Towards Open-Shell Near-Infrared Materials for Efficient Photothermal Therapy.

Open-shell radicals are promising near-infrared (NIR) photothermal agents (PTAs) owing to their easily accessible narrow band gaps, but their stabilization and functionalization remain challenging. Herein, highly stable π-extended nickel corrole radicals with [4n+1] π systems are synthesized and used to prepare NIR-absorbing PTAs for efficient phototheranostics. The light-harvesting ability of corrole radicals gradually improves as the number of fused benzene rings on ß-pyrrolic locations increases radially, with naphthalene- and anthracene-fused radicals and their one-electron oxidized [4n] π cations exhibiting panchromatic visible-to-NIR absorption. The extremely low doublet excited states of corrole radicals promote heat generation via nonradiative decay. By encapsulating naphthocorrole radicals with amphiphilic polymer, water-soluble nanoparticles Na-NPs are produced, which exhibit outstanding photostability and high photothermal conversion efficiency of 71.8 %. In vivo anti-tumor therapy results indicate that Na-NPs enable photoacoustic imaging of tumors and act as biocompatible PTAs for tumor ablation when triggered by 808 nm laser light. The "aromatic-ring fusion" strategy for energy-gap tuning of corrole radicals opens a new platform for developing robust NIR-absorbing photothermal materials.

Highly Stable Neutral Corrole Radical: Amphoteric Aromatic-Antiaromatic Switching and Efficient Photothermal Conversion.

The preparation of novel stable radical systems that survive and may be manipulated under harsh conditions is essential for their practical applications, such as energy storage and conversion materials. Here, we present a facile synthesis of an electrically neutral benzo-fused nickel corrole radical that shows remarkable photo- and thermal stability. The carbon-based organic radical character was confirmed using electron spin resonance and spin population analyses. This radical may be reversibly converted to its aromatic or antiaromatic ion via a one-electron redox process, as indicated by nuclear magnetic resonance chemical shifts and theoretical calculations. Notably, the antiaromatic state is stable, showing intense ring currents with complex pathways. The spectroscopic characteristics and calculated molecular orbitals of the corrole radical exhibit a combination of aromatic and antiaromatic features. On the basis of the aromatic light-harvesting property and antiaromatic emission-free character, the corrole radical exhibits highly robust, efficient photothermal energy conversion in water after encapsulation within nanoparticles, with the unpaired spin simultaneously retained. These results provide a fundamental understanding of the relationship between the (anti)aromaticity and photophysical properties of a porphyrinoid radical and a promising platform for the design of radical-based functional materials.

Axial-Chiral BINOL Multiferroic Crystals with Coexistence of Ferroelectricity and Ferroelasticity.

Chirality exists everywhere from natural amino acids to particle physics. The introduction of point chirality has recently been shown to be an efficient strategy for the construction of molecular ferroelectrics. In contrast to point chirality, however, axial chirality is rarely used to design ferroelectrics so far. Here, based on optically active 1,1'-bi-2-naphthol (BINOL), which has been applied extensively as a versatile chiral reagent in asymmetric catalysis, chiral recognition, and optics, we successfully design a pair of axial-chiral BINOL multiferroics, (R)-BINOL-DIPASi and (S)-BINOL-DIPASi. They experience a 2F1-type full ferroelectric/ferroelastic phase transition at a high temperature of 362 and 363 K, respectively. Piezoelectric force microscopy and polarization-voltage hysteresis loops demonstrate their ferroelectric domains and domain switching, and polarized light microscopy visualizes the evolution of stripe-shaped ferroelastic domains. The axial-chiral BINOL building block promotes the generation of the polar structure and ferroelectricity, and the organosilicon component increases the rotational energy barrier and thus the phase transition temperature. This work presents the first axial-chiral high-temperature multiferroic crystals, offering an efficient path for designing molecular multiferroics through the introduction of axial chirality.

Dwarf mice as models for reproductive ageing research.

Dwarf mice are characterized by extremely long lifespan, delayed ovarian ageing, altered metabolism, lower age-related oxidative damage and cancer incidence rate. Snell dwarf, Ames dwarf and growth hormone receptor knockout mice are three commonly used models. Despite studies focusing on ageing and metabolism, the reproductive features of female dwarf mice have also attracted interest over the last decade. Female Snell and Ames dwarf mice have regular oestrous cycles and ovulation rates, as in normal mice, but with a larger ovarian reserve and delayed ovarian ageing. The primordial follicle reserve in dwarf mice is greater than in normal littermates. Anti-Müllerian hormone (AMH) concentration is seven times higher in Ames dwarf mice than in their normal siblings, and ovarian transcriptomic profiling showed distinctive patterns in older Ames dwarf mice, especially enriched in inflammatory and immune response-related pathways. In addition, microRNA profiles also showed distinctive differences in Ames dwarf mice compared with normal control littermates. This review aims to summarize research progress on dwarf mice as models in the reproductive ageing field. Investigations focusing on the mechanisms of their reserved reproductive ability are much needed and are expected to provide additional molecular biological bases for the clinical practice of reproductive medicine in women.

Preimplantation genetic testing for structural rearrangement based on low-coverage next-generation sequencing accurately discriminates between normal and carrier embryos for patients with translocations.

RESEARCH QUESTION: Can preimplantation genetic testing for structural rearrangement (PGT-SR) based on low-coverage next-generation sequencing (NGS) accurately discriminate between normal and carrier embryos of reciprocal translocation (RecT) and Robertsonian translocation (RobT)? DESIGN: A total of 109 couples with RecT or RobT were included in this study. The ages, bad obsteric histories (BOH), blood karyotype and IVF cycle information, including the number of cumulus-oocyte complexes, metaphase II oocytes, two pronuclei oocytes and blastocysts were recorded. 0.1 × whole genome sequencing (WGS) of embryos followed by copy number variation (identifying unbalanced/balanced) and 2 × WGS of parents and embryos followed by haplotype analysis (discriminating between normal and carrier) were carried out in PGT-SR cycles. The embryos without translocation were transferred and clinical outcomes evaluated. RESULTS: Among all the couples in this study, 67 patients had RecT and 42 had RobT. After unbalanced and balanced detection, 103 balanced embryos underwent a further normal and carrier discrimination procedure, and 53 normal embryos were identified. Finally, 32 normal embryos were transferred, with an ongoing pregnancy rate of 46.88% (15/32). All ongoing pregnancies underwent amniocentesis, and the amninocentesis karyotyping results showed 100% concordance with PGT-SR diagnosis. CONCLUSIONS: Our low-coverage NGS-based PGT-SR method can accurately discriminate between normal and carrier status of balanced embryos. The method is cost-effective and has broad clinical applicability.

Genetic screening of Chinese patients with hydatidiform mole by whole-exome sequencing and comprehensive analysis.

PURPOSE: We aim to explore if there are any other candidate genetic variants in patients with a history of at least one hydatidiform mole (HM) besides the well-known variants in NLRP7 and KHDC3L. METHODS: The diagnosis of HM type was based on histopathology, and available HM tissues were collected for short tandem repeat (STR) genotyping to verify the diagnosis. DNA extracted from blood samples or decidual tissues of the 78 patients was subjected to whole-exome sequencing (WES). RESULTS: We identified five novel variants in NLRP7, two novel variants in KHDC3L, and a chromosome abnormality covering the KHDC3L locus among patients with HM. We found that patients with HM who carried heterozygous variants in KHDC3L had a chance of normal pregnancy. We also detected four novel genetic variants in candidate genes that may be associated with HM. CONCLUSION: Our study enriched the spectrum of variants in NLRP7 and KHDC3L in Chinese HM patients and provided a new outlook on the effects of heterozygous variants in KHDC3L. The novel candidate genetic variants associated with HMs reported in this study will also contribute to further research on HMs.

Reusable molecularly imprinted electrochemiluminescence assay for kanamycin based on ordered mesoporous carbon loaded with indium oxide nanoparticles and carbon quantum dots.

A highly sensitive kanamycin electrochemiluminescence (ECL) switch sensor was constructed. A signal element consisting of ordered mesoporous carbon loaded with indium oxide nanoparticles/carbon quantum dots (OMC/In2O3/C-dots) was assembled on the surface of a gold electrode. Then, a molecularly imprinted polymer (MIP) was prepared on the modified electrode surface using kanamycin as the template molecule and o-aminophenol as the functional monomer. After kanamycin elution, the prepared sensor retained specific kanamycin recognition sites. OMC/In2O3 effectively amplified the ECL signal of the C-dots, thereby enhancing the detection sensitivity, whereas kanamycin quenched the signal. Therefore, the imprinted sites acted as a switch, providing a new method for detecting kanamycin. Under the optimal experimental conditions, the concentration of kanamycin was proportional to the degree of ECL quenching within a linear range of 5-4500 × 10-12 mol L-1 at 0.8 V (vs. Ag/AgCl electrode electrode), and the detection limit was 5.8 × 10-13 mol L-1. When applied to the detection of kanamycin in actual samples, such as chicken, duck, pork, and milk, the recovery for spiked samples was in the range 92.7-110%.

An engineered abcb4 expression model reveals the central role of NF-κB in the regulation of drug resistance in zebrafish.

Multi-drug resistance (MDR) is a phenomenon that tumor cells are exposed to a chemotherapeutic drug for a long time and then develop resistance to a variety of other anticancer drugs with different structures and different mechanisms. The in vitro studies of tumor cell lines cannot systematically reflect the role of MDR gene in vivo, and the cost of in vivo studies of transgenic mice as animal models is high. Given the myriad merits of zebrafish relative to other animal models, we aimed to establish a screening system using zebrafish stably expressing ATP-binding cassette (ATP-cassette) superfamily transporters and unveil the potential regulatory mechanism. We first used the Tol2-mediated approach to construct a Tg (abcb4:EGFP) transgenic zebrafish line with ATP-binding cassette (ABC) subfamily B member 4 (abcb4) gene promoter to drive EGFP expression. The expression levels of abcb4 and EGFP were significantly increased when Tg(abcb4:EGFP) transgenic zebrafish embryos were exposed to doxorubicin (DOX) or vincristine (VCR), and the increases were accompanied by a marked decreased accumulation of rhodamine B (RhB) in embryos, indicating a remarkable increase in DOX or VCR efflux. Mechanistically, Akt and Erk signalings were activated upon the treatment with DOX or VCR. With the application of Akt and Erk inhibitors, drug resistance was reversed with differing responsive effects. Notably, downstream NF-κB played a central role in the regulation of abcb4-mediated drug resistance. Taken together, the data indicate that the engineered Tg(abcb4:EGFP) transgenic zebrafish model is a new platform for screening drug resistance in vivo, which may facilitate and accelerate the process of drug development.

Homochiral Multiferroic Cyanido-Bridged Dimetallic Complexes Assembled by C-F⋠⋠⋠K Interactions.

Cyanido-bridged dimetallic complexes are attracting attention due to their varied structures and properties. However, homochiral cyanido-bridged dimetallic complexes are rare, and making them ferroelectric is a great challenge. Introducing C-F⋅⋅⋅K interactions between the guest chiral cations and the host [KFe(CN)6 ]2- framework, gives three-dimensional cyanido-bridged dimetallic multiferroics, [R- and S-3-fluoropyrrolidinium]2 [KFe(CN)6 ] (R- and S-3-FPC). The mirror-symmetric vibrational circular dichroism (VCD) signal shows their enantiomeric nature. R- and S-3-FPC crystallize in the same chiral-polar space group P21 at 298 K. Piezoresponse force microscopy (PFM), polarizing optical microscopy, and temperature-dependent second-harmonic generation (SHG) measurements show their multiferroic properties (the coexistence of ferroelectricity and ferroelasticity), in line with the Aizu notation of 222F2. R-3-FPC shows excellent ferroelectricity with saturated polarization up to 9.4 µC cm-2 .

The First Chiro-Inositol Organosilicon Ferroelectric Crystal.

Organosilicons have been used extensively in aerospace, electronics, food, medicine and other fields, due to their low viscosity, hydrophobicity, corrosion resistance, non-toxic, and physiologically inert features. Despite extensive interest, however, organosilicon ferroelectric crystals have never been found. Here, by using the chemical design strategy, we successfully obtained a molecular ferroelectric D-chiro-inositol-SiMe3 with polar P43 symmetry, whose spontaneous polarization can be electrically switchable on thin film. The introduction of organosilicon groups endows the thin films with excellent softness, ductility and flexibility (extremely low hardness of 72.8 MPa and small elastic modulus of 5.04 GPa) that are desirable for biomedical and human-compatible applications. As the first case of organosilicon ferroelectric crystal to date, this work offers a new structural paradigm for molecular ferroelectrics, and highlights their potential for flexible bio-electronic applications.

Large Electrostrictive Coefficient in a Two-Dimensional Hybrid Perovskite Ferroelectric.

Two-dimensional (2D) hybrid organic-inorganic perovskites (HOIPs) are attracting tremendous interest for their great scientific and technological potential in photovoltaics and optoelectronics. Although the ferroelectricity in 2D HOIPs has been greatly developed, however, to date no phosphonium-based 2D HOIP ferroelectrics have yet been found. Meanwhile, electrostriction plays an important role in the electromechanical behavior of ferroelectrics, while it has never been reported for 2D HOIP ferroelectrics. Here, we present the first phosphonium-based 2D HOIP ferroelectric (EATMP)PbBr4 (EATMP = (2-aminoethyl)trimethylphosphanium) with a direct bandgap of 2.84 eV. Notably, (EATMP)PbBr4 possesses a high Curie temperature of 534 K, which is the highest among all reported 2D HOIP ferroelectrics. Moreover, it exhibits a large electrostrictive coefficient of about 3.96 m4 C-2 as well, far exceeding those of PVDF (1.3 m4 C-2) and inorganic ones (∼0.034-0.096 m4 C-2). With excellent ferroelectric and piezoelectric properties and the merit of easy fabrication, (EATMP)PbBr4 shows great potential in applications for future smart devices of actuators, transducers, and sensors.