HELQ deficiency impairs the induction of primordial germ cell-like cells.

Helicase POLQ-like (HELQ) is a DNA helicase essential for the maintenance of genome stability. A recent study identified two HELQ missense mutations in some cases of infertile men. However, the functions of HELQ in the process of germline specification are not well known and whether its function is conserved between mouse and human remains unclear. Here, we revealed that Helq knockout (Helq-/-) could significantly reduce the efficiency of mouse primordial germ cell-like cell (PGCLC) induction. In addition, Helq-/- embryonic bodies exhibited a severe apoptotic phenotype on day 6 of mouse PGCLC induction. p53 inhibitor treatment could partially rescue the generation of mouse PGCLCs from Helq mutant mouse embryonic stem cells. Finally, the genetic ablation of HELQ could also significantly impede the induction of human PGCLCs. Collectively, our study sheds light on the involvement of HELQ in the induction of both mouse and human PGCLCs, providing new insights into the mechanisms underlying germline differentiation and the genetic studies of human fertility.

Insights on updates in sodium alginate/MXenes composites as the designer matrix for various applications: A review.

Advancements in two-dimensional materials, particularly MXenes, have spurred the development of innovative composites through their integration with natural polymers such as sodium alginate (SA). Mxenes exhibit a broad specific surface area, excellent electrical conductivity, and an abundance of surface terminations, which can be combined with SA to maximize the synergistic effect of the materials. This article provides a comprehensive review of state-of-the-art techniques in the fabrication of SA/MXene composites, analyzing the resulting structural and functional enhancements with a specific focus on advancing the design of these composites for practical applications. A detailed exploration of SA/MXene composites is provided, highlighting their utility in various sectors, such as wearable electronics, wastewater treatment, biomedical applications, and electromagnetic interference (EMI) shielding. The review identifies the unique advantages conferred by incorporating MXene in these composites, examines the current challenges, and proposes future research directions to understand and optimize these promising materials thoroughly. The remarkable properties of MXenes are emphasized as crucial for advancing the performance of SA-based composites, indicating significant potential for developing high-performance composite materials.

Single-crystal oxygen-rich bismuth oxybromide nanosheets with highly exposed defective {10-1} facets for the selective oxidation of toluene under blue LED irradiation.

Reactive radicals are crucial for activating inert and low-polarity C(sp3)-H bonds for the fabrication of high value-added products. Herein, novel single-crystal oxygen-rich bismuth oxybromide nanosheets (Bi4O5Br2 SCNs) with more than 85 % {10-1} facets exposure and oxygen defects were synthesized via a facile solvothermal route. The Bi4O5Br2 SCNs demonstrated excellent photocatalytic performance in the selective oxidation of toluene under blue light. The yield of benzaldehyde was 1876.66 µmol g-1 h-1, with a selectivity of approximately 90 %. Compared to that of polycrystalline Bi4O5Br2 nanosheets (Bi4O5Br2 PCNs), the activity of Bi4O5Br2 SCNs exhibit a 21-fold increase. Experimental studies and density functional theory (DFT) calculations have demonstrated that the defect Bi4O5Br2 (10-1) facets exhibits exceptional adsorption properties for O2 molecules. In addition, the single-crystal structure in the presence of surface defects significantly increases the separation and transport of photogenerated carriers, resulting in the effective activation of adsorbed O2 into superoxide radicals (•O2-). Subsequently, the positively charged phenylmethyl H is readily linked to the negatively charged superoxide radical anion, thereby activating the CH bond. This study offers a fresh perspective and valuable insights into the development of efficient molecular oxygen-activated photocatalysts and their application in the selective catalytic conversion of aromatic C(sp3)-H bonds.

An integrated multi-omics analysis reveals osteokines involved in global regulation.

Bone secretory proteins, termed osteokines, regulate bone metabolism and whole-body homeostasis. However, fundamental questions as to what the bona fide osteokines and their cellular sources are and how they are regulated remain unclear. In this study, we analyzed bone and extraskeletal tissues, osteoblast (OB) conditioned media, bone marrow supernatant (BMS), and serum, for basal osteokines and those responsive to aging and mechanical loading/unloading. We identified 375 candidate osteokines and their changes in response to aging and mechanical dynamics by integrating data from RNA-seq, scRNA-seq, and proteomic approaches. Furthermore, we analyzed their cellular sources in the bone and inter-organ communication facilitated by them (bone-brain, liver, and aorta). Notably, we discovered that senescent OBs secrete fatty-acid-binding protein 3 to propagate senescence toward vascular smooth muscle cells (VSMCs). Taken together, we identified previously unknown candidate osteokines and established a dynamic regulatory network among them, thus providing valuable resources to further investigate their systemic roles.

Anti-inflammatory and Neuroprotective α-Pyrones from a Marine-Derived Strain of the Fungus Arthrinium arundinis and Their Heterologous Expression.

Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new (1 and 2) and four known (3-6) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus Arthrinium arundinis. Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster (alt) for alternapyrones was identified from A. arundinis ZSDS-F3 and validated by heterologous expression in Aspergillus nidulans A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2' could convert the methyl group 26-CH3 to a carboxyl group to produce 4 from 3. Another cytochrome P450 monooxygenase, Alt3', catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce 1, 2, 5, and 6 from 4. Alternapyrone G (1) not only suppressed M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 microglia but also stimulated dendrite regeneration and neuronal survival after Aß treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer's disease drug discovery.

Surface-supported metal-organic frameworks with geometric topological diversity via scanning tunneling microscopy.

Surface-supported metal-organic frameworks (SMOFs) are long-range ordered periodic 2D lattice layers formed by inorganic metal nodes and organic ligands via coordination bonds on substrate surfaces. The atomic resolution STM lays a solid foundation for the conception and construction of SMOFs with large area, stable structure, and special function. In this review, the cutting-edge research of SMOFs from design strategy, preparation process, and how to accurately achieve structural and functional diversity are reviewed. Furthermore, we focus on the design and construction of novel and fascinating periodic and fractal structures, in which some typical honeycomb structures, Kagome lattice, hexagonal geometry, and Sierpinski triangles are summarized, and the related prospects for designing functional nanoscale systems and architectures are prospected. Finally, the challenges faced in the design and synthesis of SMOFs are denoted, and the application prospect and development trend of SMOFs are forecasted based on the current research status.

Symmetry of Pyridine Derivatives Controlled Two-Dimensional Nanostructural Diversity by Co-Assembly with Aromatic Carboxylic Acids.

The self-assembly behaviors of aromatic carboxylic acids are commonly investigated at the liquid/solid interfaces because of their rigid skeletons and both hydrogen-bond donors and receptors. However, self-assemblies of aromatic carboxylic acids with low symmetry and interactions between carboxylic acid and pyridine derivatives are worth exploring. In this work, the self-assembled structural transitions of a kind of low-symmetric aromatic carboxylic acid (H4QDA) are regulated by the coadsorption of two pyridine derivatives (DPE and T4PT) with different symmetry, which are investigated by scanning tunneling microscopy under ambient conditions. For the H4QDA/DPE system, the grid structure appears. For the H4QDA/T4PT system, the coassembled morphologies display an obvious concentration dependence. With the increase of solution concentration of T4PT, three coassembled patterns (network structure, chiral linear structure, and brick-like structure) are observed. Corresponding structural models suggest that the O-H···N hydrogen bonds have great contributions to stabilizing these coassembled structures. Our studies will help to explore the complexity, diversity, and functionality of multiple component systems and are conducive to further understanding the underlying mechanisms in the assembly process.

Study on a Highly Thermostable Dy3+-Activated Borophosphate Phosphor.

Constructing a phosphor with multifunctional applications is an imperative challenge. Especially, highly thermostable luminescence of phosphor is indispensable for stable white-light-emitting diodes (LEDs). Nevertheless, good thermal quenching resistance behavior is unfavorable for a fluorescence intensity ratio (FIR)-based optical temperature sensor. Herein, a highly thermostable Ba3(ZnB5O10)PO4 (BZBP)-based phosphor is successfully achieved via replacing Ba2+ with Dy3+, demonstrating simultaneously promising lighting and thermometry utilizations. Under the excitation of 350 nm, the title phosphor only loses 12% of the initial intensity when the temperature is up to 473 K, ensuring sufficient luminescence thermostability for white-LED lighting. The white-LED device fabricated using the title phosphor emits high-quality white light with a high color rendering index (Ra = 93) and low correlated color temperature (CCT = 3996 K). Meanwhile, the yellow and blue emission intensities demonstrate a downtrend difference with rising temperature. Temperature sensing properties are assessed through FIR technology. The maximal relative sensitivity reaches as high as 0.0379 K-1 at 298 K. These results reveal that the title phosphor has a great potential for indoor lighting and thermometry applications.

ANGPTL4 binds to the leptin receptor to regulate ectopic bone formation.

Leptin protein was thought to be unique to leptin receptor (LepR), but the phenotypes of mice with mutation in LepR [db/db (diabetes)] and leptin [ob/ob (obese)] are not identical, and the cause remains unclear. Here, we show that db/db, but not ob/ob, mice had defect in tenotomy-induced heterotopic ossification (HO), implicating alternative ligand(s) for LepR might be involved. Ligand screening revealed that ANGPTL4 (angiopoietin-like protein 4), a stress and fasting-induced factor, was elicited from brown adipose tissue after tenotomy, bound to LepR on PRRX1+ mesenchymal cells at the HO site, thus promotes chondrogenesis and HO development. Disruption of LepR in PRRX1+ cells, or lineage ablation of LepR+ cells, or deletion of ANGPTL4 impeded chondrogenesis and HO in mice. Together, these findings identify ANGPTL4 as a ligand for LepR to regulate the formation of acquired HO.

Surface/interfacial transport through pores control desalination mechanisms in 2D carbon-based membranes.

The shortage of freshwater is a critical concern for contemporary society, and reverse osmosis desalination technology has gathered considerable attention as a potential solution to this problem. It has been recognized that the desalination process involving water flow through angstrom-sized pores has tremendous potential. However, it is challenging to obtain angstrom-sized pore structures with internal mass transfer and surface/interface properties matching the application conditions. Herein, a two-dimensional (2D) zeolite-like carbon structure (Carzeo-ANG) was constructed with unique angstrom-sized pores in the zeolite structure; then, the surface/interfacial transport behavior and percolation effect of the Carzeo-ANG desalination membrane were evaluated by density functional theory (DFT) calculations and classical molecular dynamics. The first-principles calculations in density functional theory were implemented through the Vienna ab initio simulation package (VASP), which is a commercial package for the simulation of carbon-based materials. The results show that Carzeo-ANG is periodically distributed with angstrom-sized pores (effective diameter = 5.4 Å) of dodecacyclic carbon rings, which ensure structural stability while maintaining sufficient mechanical strength. The remarkable salt-ion adsorption properties and mass transfer activity combined with the reasonable density distribution and free energy barrier for water molecules endow the membrane with superior desalination ability. At the pressure of 80 MPa, the rejection efficiency of Cl- and Na+ were 100% and 96.25%, and the membrane could achieve a water flux of 132.71 L cm-2 day-1 MPa-1. Moreover, the interconnected electronic structure of Carzeo-ANG imparts a self-cleaning effect.

In Situ Hydrogel Polymerization to Form a Flexible Polysaccharide Synergetic Binder Network for Stabilizing SiOx/C Anodes.

Today, the commercial application of silicon oxides (SiOx, 1 < x < 2) in lithium-ion batteries (LIBs) still faces the challenge of rapid performance degradation. In this work, by integrating hydrothermal and physicomechanical processes, water-soluble locust bean gum (LBG) and xanthan gum (XG) are utilized to in situ form an LBG@XG binder network to improve the performance of SiOx/C anodes. As a synergy of LBG and XG polysaccharides in hydrogel polymerization, LBG@XG can tightly wrap around SiOx/C particles to prevent plate damage. The flexible SiOx/C anode with the LBG@XG binder exhibits capacity retentions of 74.1% and 76.4% after 1000 cycles at 0.5 A g-1 and 1 A g-1, respectively. The full battery capacity remains stable for 100 cycles at 1 C and the rate performance is excellent (103 mAh g-1 at 3 C). This LBG@XG is demonstrated to be highly electronegative and has a strong attraction to SiOx/C particles, thereby reducing the expansion and increasing the stability of the SiOx/C anodes when coupled with the flexible binder network. In addition to the promising LBG@XG binder, this work also provides a research idea for developing green water-based binders suitable for application in the SiOx/C anodes of LIBs.

Single-cell multi-omics sequencing of human spermatogenesis reveals a DNA demethylation event associated with male meiotic recombination.

Human spermatogenesis is a highly ordered process; however, the roles of DNA methylation and chromatin accessibility in this process remain largely unknown. Here by simultaneously investigating the chromatin accessibility, DNA methylome and transcriptome landscapes using the modified single-cell chromatin overall omic-scale landscape sequencing approach, we revealed that the transcriptional changes throughout human spermatogenesis were correlated with chromatin accessibility changes. In particular, we identified a set of transcription factors and cis elements with potential functions. A round of DNA demethylation was uncovered upon meiosis initiation in human spermatogenesis, which was associated with male meiotic recombination and conserved between human and mouse. Aberrant DNA hypermethylation could be detected in leptotene spermatocytes of certain nonobstructive azoospermia patients. Functionally, the intervention of DNA demethylation affected male meiotic recombination and fertility. Our work provides multi-omics landscapes of human spermatogenesis at single-cell resolution and offers insights into the association between DNA demethylation and male meiotic recombination.

Genome Mining and Biosynthetic Reconstitution of Fungal Depsidone Mollicellins Reveal a Dual Functional Cytochrome P450 for Ether Formation.

Depsidones are significant in structural diversity and broad in biological activities; however, their biosynthetic pathways have not been well understood and have attracted considerable attention. Herein, we heterologously reconstituted a depsidone encoding gene cluster from Ovatospora sp. SCSIO SY280D in Aspergillus nidulans A1145, leading to production of mollicellins, a representative family of depsidones, and discovering a bifunctional P450 monooxygenase that catalyzes both ether formation and hydroxylation in the biosynthesis of the mollicellins. The functions of a decarboxylase and an aromatic prenyltransferase are also characterized to understand the tailoring modification steps. This work provides important insights into the biosynthesis of mollicellins.

A fast chemical reprogramming system promotes cell identity transition through a diapause-like state.

Cellular reprogramming by only small molecules holds enormous potentials for regenerative medicine. However, chemical reprogramming remains a slow process and labour intensive, hindering its broad applications and the investigation of underlying molecular mechanisms. Here, through screening of over 21,000 conditions, we develop a fast chemical reprogramming (FCR) system, which significantly improves the kinetics of cell identity rewiring. We find that FCR rapidly goes through an interesting route for pluripotent reprogramming, uniquely transitioning through a developmentally diapause-like state. Furthermore, FCR critically enables comprehensive characterizations using multi-omics technologies, and has revealed unexpected important features including key regulatory factors and epigenetic dynamics. Particularly, activation of pluripotency-related endogenous retroviruses via inhibition of heterochromatin significantly enhances reprogramming. Our studies provide critical insights into how only environmental cues are sufficient to rapidly reinstate pluripotency in somatic cells, and make notable technical and conceptual advances for solving the puzzle of regeneration.

Dissolution mechanism of Fe3O4 scale by 1-hydroxyethane-1,1-diphosphonic acid: an ab initio molecular metadynamics study.

Using the ab initio molecular metadynamics method, the adsorption of the structure of 1-hydroxyethane-1,1-diphosphonic acid (HEDP) on the Fe3O4 surface and subsequent detachment of Fe atoms from the surface were simulated, and the dissolution mechanism by which HEDP dissolves Fe3O4 scale at room temperature while other organic acids cannot was elucidated. The adsorbed hydroxyl groups, water and HEDP on the Fe3O4 surface play a synergistic role in detaching the Fe ions, which increases the coordination number of the Fe atoms and weakens the original Fe-O bond strength. In addition, the strong coordination ability and flexible molecular structure of HEDP also facilitate dissolution of Fe3O4 scale by breaking down the chemical bonds and forming Fe-HEDP complexes. The free energy surface for the dissolution reaction shows a low barrier, and the descaling reaction is easily accomplished.

Molecular structures of 1-hydroxyethane-1,1-diphosphonic acid for removing calcium sulfate scale under different pH conditions.

As an important descaling agent, 1-hydroxyethane-1,1-diphosphonic acid (HEDP) is capable of dissolving calcium sulfate scale when the pH of HEDP solution is adjusted from acidic to weakly alkaline. The molecular structures of Ca-HEDP complexes were determined to understand the impact of pH on the dissolution of calcium sulfate scale. The structures of the complexes revealed that the two phosphonic acid groups and the hydroxyl group of HEDP each provide one O atom to coordinate with the Ca ion to form a stable three-coordinate configuration under alkaline conditions. The electronic structures were investigated by interaction region indicator analysis, atoms in molecules analysis, electron localization function and natural population analysis. The deprotonation of the phosphonic acid group enhances the binding of coordinated O atoms and Ca ions as the pH increases, and weak alkalinity is the optimal process condition as strong alkaline conditions result in the precipitation of hydroxide and Ca ions.

Two tigers cannot live on the same mountain: The impact of the second largest shareholder on controlling shareholder's tunneling behavior.

Under the current corporate governance model, the second largest shareholder (SLS) is a very special, common and important presence, which becomes an important counterweight to the controlling shareholder (CS). Through a game matrix, this paper explains whether the SLS will supervise the CS's tunneling behavior. Based on this, we empirically examine the effect of the SLS on CS's tunneling behavior in Chinese listed firms between 2010 and 2020. The results indicate that the SLS significantly inhibits CS's tunneling behavior. In addition, the heterogeneity analysis reveals that the negative effect of the SLS on CS's tunneling behavior is concentrated in non-state-owned enterprises (NSOEs) and enterprises located in regions with better business environment. This paper provides a reference for resolving the current "conflict of interest" among multiple large shareholders (MLSs), as well as evidence to support the governance role of the SLS in listed firms with MLSs.

Brexpiprazole suppresses cell proliferation and de novo lipogenesis through AMPK/SREBP1 pathway in colorectal cancer.

OBJECTIVE: In the present study, we investigated the role of brexpiprazole on cell proliferation and lipogenesis in colorectal cancer (CRC) and its molecular mechanism. METHODS: The effect of brexpiprazole on CRC cell proliferation was determined by CCK-8, EdU assay, cell clone formation. The flow cytometry was evaluated cell cycle. Differential expression genes (DEGs) were identified by RNA-seq assay after treating HCT116 cells with or without 20 µM brexpiprazole for 24 h. Then, the top 120 DEGs were analyzed by GO and KEGG enrichment analysis. After that, Oil red O staining and the levels of total cholestenone and triglyceride were measured to assess lipogenesis capacity in CRC cells. The related molecules of cell proliferation, lipogenic and AMPK/SREBP1 signal pathways were measured by q-PCR, western blot and immunohistochemical staining. RESULTS: Brexpiprazole remarkably suppressed cell proliferation, lipogenesis, and induced cell cycle arrest in CRC. The underlying mechanisms probably involved the suppression of SREBP1 and the stimulation of AMPK. CONCLUSION: Brexpiprazole inhibited cell proliferation and de novo lipogenesis through AMPK/SREBP1 pathway in CRC.

Engineered circular guide RNAs boost CRISPR/Cas12a- and CRISPR/Cas13d-based DNA and RNA editing.

BACKGROUND: The CRISPR/Cas12a and CRISPR/Cas13d systems are widely used for fundamental research and hold great potential for future clinical applications. However, the short half-life of guide RNAs (gRNAs), particularly free gRNAs without Cas nuclease binding, limits their editing efficiency and durability. RESULTS: Here, we engineer circular free gRNAs (cgRNAs) to increase their stability, and thus availability for Cas12a and Cas13d processing and loading, to boost editing. cgRNAs increases the efficiency of Cas12a-based transcription activators and genomic DNA cleavage by approximately 2.1- to 40.2-fold for single gene editing and 1.7- to 2.1-fold for multiplexed gene editing than their linear counterparts, without compromising specificity, across multiple sites and cell lines. Similarly, the RNA interference efficiency of Cas13d is increased by around 1.8-fold. In in vivo mouse liver, cgRNAs are more potent in activating gene expression and cleaving genomic DNA. CONCLUSIONS: CgRNAs enable more efficient programmable DNA and RNA editing for Cas12a and Cas13d with broad applicability for fundamental research and gene therapy.