Evolved histone tail regulates 53BP1 recruitment at damaged chromatin.

The master DNA damage repair histone protein, H2AX, is essential for orchestrating the recruitment of downstream mediator and effector proteins at damaged chromatin. The phosphorylation of H2AX at S139, γH2AX, is well-studied for its DNA repair function. However, the extended C-terminal tail is not characterized. Here, we define the minimal motif on H2AX for the canonical function in activating the MDC1-RNF8-RNF168 phosphorylation-ubiquitination pathway that is important for recruiting repair proteins, such as 53BP1 and BRCA1. Interestingly, H2AX recruits 53BP1 independently from the MDC1-RNF8-RNF168 pathway through its evolved C-terminal linker region with S139 phosphorylation. Mechanistically, 53BP1 recruitment to damaged chromatin is mediated by the interaction between the H2AX C-terminal tail and the 53BP1 Oligomerization-Tudor domains. Moreover, γH2AX-linker mediated 53BP1 recruitment leads to camptothecin resistance in H2AX knockout cells. Overall, our study uncovers an evolved mechanism within the H2AX C-terminal tail for regulating DNA repair proteins at damaged chromatin.

Scalable Fabrication of Structurally Stable Polymer Film with Excellent UV-Shielding, Fluorescent, and Antibacterial Capabilities.

This research presents a new approach to facilely fabricating a multifunctional film using polyvinyl alcohol (PVA) as the base material. The film is modified chemically to incorporate various desirable properties such as high transparency, UV-shielding, antibacterial activity, and fluorescence. The fabrication process of this film is straightforward and efficient. The modified film showed exceptional UV-blocking capability, effectively blocking 100% of UV radiation. It also exhibits strong antibacterial properties. Additionally, the film emitted bright blue fluorescence, which can be useful in various optical and sensing applications. Despite the chemical modification, the film retained the excellent properties of PVA, including high transparency (90%) at 550 nm and good mechanical strength. Furthermore, it demonstrated remarkable stability even under harsh conditions such as exposure to long-term UV radiation, extreme temperatures (-40 or 120 °C), or immersion in different solvents. Overall, this work showcases a promising strategy to develop versatile, structurally stable, transparent, and flexible polymer films with multiple functionalities. These films have potential applications in various fields that require protection, such as packaging materials, biomedical devices, and optical components.

Specific expression profile of follicular fluid-derived exosomal microRNAs in patients with diminished ovarian reserve.

BACKGROUND: Diminished ovarian reserve (DOR) is defined as a reduction in ovarian reserve and oocyte quality. The pathophysiology of DOR has not been completely explained as of yet. Scholars have uncovered a large number of exosomes that have been detected in follicular fluid, and exosomal miRNAs have been proven to play a critical role in controlling ovarian disorders and follicle formation. We focused on the expression profile of follicular fluid-derived exosomal microRNAs (miRNAs) and attempted to understand if their role is connected to the pathomechanism of DOR. METHODS: The follicular fluid-derived differentially expressed exosomal miRNAs (DEmiRs) between patients with DOR and those with normal ovarian function were investigated using the next-generation sequencing (NGS) method. The main metabolic and signaling pathways of DEmiRs were identified using the KEGG pathway database, disease ontology (DO) analysis, and gene ontology (GO) analysis. In the end, a Protein-Protein Interaction (PPI) network was built to search for exosomal miRNAs and their target genes that were potentially strongly connected with DOR. RESULTS: In comparison to normal controls, 52 DEmiRs were discovered in follicular fluid-derived exosomes of DOR patients, of which 19 were up-regulated and 33 were down-regulated (|log2(fold change) |>2, P < 0.05). GO, DO analysis, and the KEGG pathway database revealed that many of these DEmiRs have broad biological roles that are connected to ovarian function and disorders. The top ten DEmiRs in terms of expression were then chosen for miRNA-mRNA interaction analysis. Totally, 8 experimentally supported miRNAs (hsa-miR-1246, hsa-miR-483-3p, hsa-miR-122-5p, hsa-miR-130b-3p, hsa-miR-342-3p, hsa-miR-625-3p, hsa-miR-675-3p, and hsa-miR-134-5p) and 126 target genes were filtrated by utilizing Cytoscape software. The module analysis findings of the PPI network showed that the main module cluster with a score > 6.0 (MCODE score = 15) had six hub genes, including IGFR, VEGFA, KRAS, ERBB2, RHOA, and PTEN (MCODE score = 11.472). CONCLUSION: Our data suggested a special expression profile of follicular fluid-derived exosomal miRNAs in patients with DOR, which was probably correlated to ovarian dysfunction and follicle formation. These results may give a unique insight into a better understanding of the molecular process in the pathogenesis of DOR or other ovarian diseases.

Glycolytic enzyme PFKFB3 regulates sphingosine 1-phosphate receptor 1 in proangiogenic glomerular endothelial cells under diabetic condition.

Glomerular angiogenesis is a characteristic feature of diabetic nephropathy (DN). Enhanced glycolysis plays a crucial role in angiogenesis. The present study was designed to investigate the role of glycolysis in glomerular endothelial cells (GECs) in a mouse model of DN. Mouse renal cortex and isolated glomerular cells were collected for single-cell and RNA sequencing. Cultured GECs were exposed to high glucose in the presence (proangiogenic) and absence of a vascular sprouting regimen. MicroRNA-590-3p was delivered by lipofectamine in vivo and in vitro. In the present study, a subgroup of GECs with proangiogenic features was identified in diabetic kidneys by using sequencing analyses. In cultured proangiogenic GECs, high glucose increased glycolysis and phosphofructokinase/fructose bisphosphatase 3 (PFKFB3) protein expression, which were inhibited by overexpressing miRNA-590-3p. Mimics of miRNA-590-3p also increased receptor for sphingosine 1-phosphate (S1pR1) expression, an angiogenesis regulator, in proangiogenic GECs challenged with high glucose. Inhibition of PFKFB3 by pharmacological and genetic approaches upregulated S1pR1 protein in vitro. Mimics of miRNA-590-3p significantly reduced migration and angiogenic potential in proangiogenic GECs challenged with high glucose. Ten-week-old type 2 diabetic mice had elevated urinary albumin levels, reduced renal cortex miRNA-590-3p expression, and disarrangement of glomerular endothelial cell fenestration. Overexpressing miRNA-590-3p via perirenal adipose tissue injection restored endothelial cell fenestration and reduced urinary albumin levels in diabetic mice. Therefore, the present study identifies a subgroup of GECs with proangiogenic features in mice with DN. Local administration of miRNA-590-3p mimics reduces glycolytic rate and upregulates S1pR1 protein expression in proangiogenic GECs. The protective effects of miRNA-590-3p provide therapeutic potential in DN treatment.NEW & NOTEWORTHY Proangiogenetic glomerular endothelial cells (GECs) are activated in diabetic nephropathy. High glucose upregulates glycolytic enzyme phosphofructokinase/fructose bisphosphatase 3 (PFKFB3) in proangiogenetic cells. PFKFB3 protects the glomerular filtration barrier by targeting endothelial S1pR1. MiRNA-590-3p restores endothelial cell function and mitigates diabetic nephropathy.

Transparent Cellulose-Based Film with High UV-Blocking Performance Fabricated by Surface Modification using Biginelli Reaction.

Efficient and sustainable ultraviolet (UV)-blocking materials are of great interest in many fields. Herein, novel cellulose-based UV-blocking films are developed via surface modification using the Biginelli reaction. The resulting films exhibited excellent visible transparency (80%) at 550 nm and superhigh UV-blocking performance, which can shield almost 100% UVA and UVB. These features are very stable even the materials are being subjected to solvents, UV irradiation, and thermal treatment. This work provides a novel and facile strategy to fabricate functional cellulose-based films with superhigh anti-ultraviolet performance.

Glomerular Endothelial Cells Are the Coordinator in the Development of Diabetic Nephropathy.

The prevalence of diabetes is consistently rising worldwide. Diabetic nephropathy is a leading cause of chronic renal failure. The present study aimed to explore the crosstalk among the different cell types inside diabetic glomeruli, including glomerular endothelial cells, mesangial cells, podocytes, and immune cells, by analyzing an online single-cell RNA profile (GSE131882) of patients with diabetic nephropathy. Differentially expressed genes in the glomeruli were processed by gene enrichment and protein-protein interactions analysis. Glomerular endothelial cells, as well as podocytes, play a critical role in diabetic nephropathy. A subgroup of glomerular endothelial cells possesses characteristic angiogenesis genes, indicating that angiogenesis takes place in the progress of diabetic nephropathy. Immune cells such as macrophages, T lymphocytes, B lymphocytes, and plasma cells also contribute to the disease progression. By using iTALK, the present study reports complicated cellular crosstalk inside glomeruli. Dysfunction of glomerular endothelial cells and immature angiogenesis result from the activation of both paracrine and autocrine signals. The present study reinforces the importance of glomerular endothelial cells in the development of diabetic nephropathy. The exploration of the signaling pathways involved in aberrant angiogenesis reported in the present study shed light on potential therapeutic target(s) for diabetic nephropathy.

Inhibition of Suv39h1/2 expression improves the early development of Debao porcine somatic cell nuclear transfer embryos.

Suppressor of variegation 3-9 homolog (Suv39h)1 and 2, Histone H3 lysine 9 trimethylation (H3K9me3)-specific methyltransferases, are mainly involved in regulating the dynamic changes of H3K9me3. Regulating Suv39h expression influences the early development of mice somatic cell nuclear transfer (SCNT) embryos, there are few reports concerning their features in domestic animals. The aim of the present study was to characterize the Suv39h function in early development of Debao porcine SCNT embryos. The global level of H3K9me3 and the expression profiles of Suv39h1/2 in porcine early embryos were analysed by immunohistochemistry and qRT-PCR methods, respectively. Their roles in cell proliferation and histone modification of Debao porcine foetal fibroblast cells (PFFs), and developmental competence of porcine SCNT embryos were investigated by shRNA technology. The methylation levels of H3K9me3 and the expression patterns of Suv39h1 and Suv39h2 were similar (p < .05), and both of them displayed higher levels in Debao porcine SCNT embryos compared with that in PA embryos. The global levels of H3K9me3 and the expressions of G9a, HDAC1 and DNMT1 were decreased by combined inhibition of Suv39h1 and Suv39h2 (p < .05), while the expression of HAT1 was increased (p < .05). Downregulation of Suv39h1/2 also promoted cell proliferation and resulted in a significant increase in the expression of CyclinA2, CyclinB and PCNA in PFFs (p < .05). Furthermore, the use of donor somatic nuclei which depleted H3K9me3 by inhibiting Suv39h1/2 expression markedly increased the cleavage rate, the blastocyst rate and the total cell number of blastocysts of Debao porcine SCNT embryos (p < .05). Altogether, the above results indicate that H3K9me3 levels and Suv39h1/2 expressions display similar patterns in porcine early embryo, and low levels of them are critical to cell proliferation of PFFs and early development of SCNT embryos.

Frequency of sodium channel genotypes and association with pyrethrum knockdown time in populations of Californian Aedes aegypti.

BACKGROUND: Since their detection in 2013, Aedes aegypti has become a widespread urban pest in California. The availability of cryptic larval breeding sites in residential areas and resistance to insecticides pose significant challenges to control efforts. Resistance to pyrethroids is largely attributed to mutations in the voltage gated sodium channels (VGSC), the pyrethroid site of action. However, past studies have indicated that VGSC mutations may not be entirely predictive of the observed resistance phenotype. METHODS: To investigate the frequencies of VGSC mutations and the relationship with pyrethroid insecticide resistance in California, we sampled Ae. aegypti from four locations in the Central Valley, and the Greater Los Angeles area. Mosquitoes from each location were subjected to an individual pyrethrum bottle bioassay to determine knockdown times. A subset of assayed mosquitoes from each location was then analyzed to determine the composition of 5 single nucleotide polymorphism (SNP) loci within the VGSC gene. RESULTS: The distribution of knockdown times for each of the five Californian populations sampled was non-parametric with potentially bimodal distributions. One group succumbs to insecticidal effects around 35-45 min and the second group lasts up to and beyond the termination of the assay (120+ min). We detected 5 polymorphic VGSC SNPs within the sampled California populations. One is potentially new and alternatively spliced (I915K), and four are documented and associated with resistance: F1534C, V1016I, V410L and S723T. The Central Valley populations (Clovis, Dinuba, Sanger and Kingsburg) are fairly homogenous with only 5% of the mosquitoes showing heterozygosity at any given position. In the Greater LA mosquitoes, 55% had at least one susceptible allele at any of the five SNP loci. The known resistance allele F1534C was detected in almost all sampled mosquitoes (99.4%). We also observe significant heterogeneity in the knockdown phenotypes of individuals with the identical VGSC haplotypes suggesting the presence of additional undefined resistance mechanisms. CONCLUSIONS: Resistance associated VGSC SNPs are prevalent, particularly in the Central Valley. Interestingly, among mosquitoes carrying all 4 resistance associated SNPs, we observe significant heterogeneity in bottle bioassay profiles suggesting that other mechanisms are important to the individual resistance of Ae. aegypti in California.

Synthesis and adsorption performance of La@ZIF-8 composite metal-organic frameworks.

In this study, ZIF-8 with a rhombic dodecahedron structure was prepared by a hydrothermal method. Then La(OH)3, was successfully loaded onto the ZIF-8 by an immersion deposition method, to form a lanthanide-based metal-organic framework (La@ZIF-8) composites. The structure and properties of La@ZIF-8 were verified by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and zeta potential measurements. The optimum process conditions are discussed within the materials and methods. The effects of initial phosphorus concentration, dosage, pH and contact reaction time on the phosphorus removal performance of the nanomaterial were investigated. The results indicated that La@ZIF-8 exhibited an excellent adsorption capacity (147.63 mg g-1) and its phosphorus removal efficiency could reach as high as 99.7%. Experimental data were interpreted using different adsorption kinetic and isotherm models. The kinetic behavior conformed to the pseudo-second-order kinetic model, which indicated the chemisorption of phosphorus by La@ZIF-8. The adsorption behavior of phosphorus by La@ZIF-8 fitted well to the Langmuir isotherm model, suggesting a monolayer chemical adsorption process. The majority of the adsorbed phosphate could be desorbed by NaOH (2 mol L-1), and the removal efficiency of the recycled La@ZIF-8 reached 90%, even after the fifth cycle. The obtained results demonstrate the great application potential of the prepared La@ZIF-8 as a fascinating adsorbent for the removal of phosphate.

Transformation Characteristics of Hydrogen-Donor Solvent Tetralin in the Process of Direct Coal Liquefaction.

The aim of this study is to investigate the transformation of hydrogen-donor solvent tetralin in the direct liquefaction process of coal. Pure tetralin liquid as well as mixture of tetralin and Wucaiwan coal (WCW) were separately reacted under a liquefaction condition, and constituents of liquid product were analyzed by GC-MS. The results show that after the tetralin liquid reacts with high-pressure hydrogen, 90% of the reaction product is in liquid state, the gaseous products mainly include alkane gas and COx gas. When the reaction temperatures were set at 380 and 420°C, respectively, the corresponding transformation rates of tetralin can be 34.72 and 52.74%. At 380°C, the tetralin mainly plays a role of passing active hydrogen, while at 420°C, it mainly occurs dehydrogenation transformation to provide active hydrogen, as well as generate naphthalene, methyl indan, and substituted benzene, etc. Taking tetralin as the hydrogen-donor solvent, the WCW was performed liquefaction reaction, and the obtained results show that the transformation rates of tetralin are 69.76 and 83.86% at liquefaction temperatures of 380 and 420°C, respectively. Tetralin mainly occur to dehydrogenation transformation to generate naphthalene, followed by methyl indan, where contents order of main constituents of the liquefaction products were: naphthalene> tetralin > methyl indan.

Boosted Visible-Light Photodegradation of Methylene Blue by V and Co Co-Doped TiO2.

In this work, TiO2 photocatalysts, co-doped with transition metal ions vanadium (V) and cobalt (Co) ((V,Co)⁻TiO2), were synthesized by the sol⁻gel method. The synthesized photocatalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), nitrogen adsorption and desorption measurement, UV-Vis absorption and photoluminescence spectrum (PL) spectra. The results show that V and Co co-doping has significant effects on sample average crystalline grain size, absorption spectrum, recombination efficiency of photo-induced electron-hole pairs (EHPs), and photocatalytic degradation efficiency of methylene blue (MB). (V,Co)⁻TiO2 photocatalyst exhibits an obvious red shift of the absorption edge to 475 nm. Photocatalytic degradation rate of (V,Co)⁻TiO2 sample for MB in 60 min is 92.12% under a Xe lamp with a cut-off filter (λ > 400 nm), which is significantly higher than 56.55% of P25 under the same conditions. The first principles calculation results show that V and Co ions doping introduces several impurity energy levels, which can modulate the location of the valence band and conduction band. An obvious lattice distortion is produced in the meantime, resulting in the decrease in photo-generated EHP recombination. Thus, (V,Co)⁻TiO2 photocatalyst performance is significantly improved.

Highly selective and sensitive methanol gas sensor based on molecular imprinted silver-doped LaFeO3 core-shell and cage structures.

Silver-doped LaFeO3 molecularly imprinted polymers (SLMIPs) were synthesized by a sol-gel method combined with molecularly imprinted technology as precursors. The precursors were then used to prepare SLMIPs cage (SLM-cage) and SLMIPs core-shell (SLM-core-shell) structures by using a carbon sphere as the template and hydrothermal synthesis, respectively. The structures, morphologies, and surface areas of these materials were determined, as well as their gas-sensing properties and related mechanisms. The SLM-cage and SLM-core-shell samples exhibited good responses to methanol gas, with excellent selectivity. The response and optimum working temperature were 16.98 °C and 215 °C, 33.7 °C and 195 °C, respectively, with corresponding response and recovery times of 45 and 50 s (SLM-cage) and 42 and 57 s (SLM-core-shell) for 5 ppm methanol gas. Notably, the SLM-cage and SLM-core-shell samples exhibited lower responses (≤5 and ≤7, respectively) to other gases, including ethanol, ammonia, benzene, acetone, and toluene. Thus, these materials show potential as practical methanol detectors.

Performance of TD-DFT for Excited States of Open-Shell Transition Metal Compounds.

Time-dependent density functional theory (TD-DFT) has been very successful in accessing low-lying excited states of closed-shell systems. However, it is much less so for excited states of open-shell systems: unrestricted Kohn-Sham based TD-DFT (U-TD-DFT) often produces physically meaningless excited states due to heavy spin contaminations, whereas restricted Kohn-Sham based TD-DFT often misses those states of lower energies. A much better variant is the explicitly spin-adapted TD-DFT (X-TD-DFT) [J. Chem. Phys. 2011, 135, 194106] that can capture all the spin-adapted singly excited states yet without computational overhead over U-TD-DFT. While the superiority of X-TD-DFT over U-TD-DFT has been demonstrated for open-shell systems of main group elements, it remains to be seen if this is also the case for open-shell transition metal compounds. Taking as benchmark the results by MS-CASPT2 (multistate complete active space second-order perturbation theory) and ic-MRCISD (internally contracted multireference configuration interaction with singles and doubles), it is shown that X-TD-DFT is indeed superior to U-TD-DFT for the vertical excitation energies of ZnH, CdH, ScH2, YH2, YO, and NbO2. Admittedly, there exist a few cases where U-TD-DFT appears to be better than X-TD-DFT. However, this is due to a wrong reason: the underestimation (due to spin contamination) and the overestimation (due to either the exchange-correlation functional itself or the adiabatic approximation to the exchange-correlation kernel) happen to be compensated in the case of U-TD-DFT. As for [Cu(C6H6)2]2+, which goes beyond the capability of both MS-CASPT2 and ic-MRCISD, X-TD-DFT revises the U-TD-DFT assignment of the experimental spectrum.

Theoretical Study of Low-Lying Ω Electronic States of PtH and PtH.

Potential energy curves of 65 and 147 low-lying Ω states of PtH and PtH+ are respectively constructed using the multireference configuration interaction with singles, doubles, and Davidson's cluster corrections (MRCISD+Q), and the spin-orbit coupling effects are considered through the state-interaction approach with relativistic effective core potential spin-orbit operators. Spectroscopic constants fitted from these curves are reported and are compared with the available experimental or theoretical values. With the aid of the theoretical results including transition dipole moments, some experimentally reported electronic states and spectral bands of PtH are analyzed and reassigned. This work provides useful reference data for future experimental and theoretical studies of PtH and PtH+.

Effects of MG132 on the in vitro development and epigenetic modification of Debao porcine somatic cell nuclear transfer embryos.

The present study was undertaken to examine the effect of MG132, a proteasome inhibitor, on the in vitro development, zygotic genome activation (ZGA) and epigenetic modification of Debao porcine somatic cell nuclear transfer (SCNT) embryos. Treatment of oocytes with 1 µM MG132 from 30 h to 42 h of maturation and SCNT embryos with 5 µM MG132 for 2 h after fusion resulted in higher blastocyst yield (36.5%) of SCNT embryos compared with the control group (11.0%). The ZGA of SCNT embryos at 2- and 4-cell stages was also enhanced by MG132 treatment through altering the RNA pol II status and increasing the expression of eIF3A and TFIIA. Meanwhile, MG132 treatment also resulted in increase of inner cell mass (ICM) and trophectoderm (TE) and total cell numbers and decrease of apoptotic cell numbers of SCNT blastocysts. Expression of BCL-2, OCT4, NANOG and CDX2 in SCNT blastocysts developed from SCNT embryos and oocytes treated with MG132 was increased significantly (P < 0.01), while the expression of pro-apoptotic BAX gene was suppressed significantly (P < 0.01). In addition, MG132 treatment not only affected the expression patterns of H3K9 acetylation, H3K4 and H3K9 trimethylation, but also regulated the relative expression of SMYD3, ASH2L, KDM5B, HAT1, HDAC1 and HDAC2 of Debao porcine SCNT embryos. These results demonstrate that MG132 treatment can improve the developmental potential of Debao porcine SCNT embryos through regulating the expression of genes related to histone acetylation and the processes of ZGA.