ADNP modulates SINE B2-derived CTCF-binding sites during blastocyst formation in mice.

CTCF is crucial for chromatin structure and transcription regulation in early embryonic development. However, the kinetics of CTCF chromatin occupation in preimplantation embryos have remained unclear. In this study, we used CUT&RUN technology to investigate CTCF occupancy in mouse preimplantation development. Our findings revealed that CTCF begins binding to the genome prior to zygotic genome activation (ZGA), with a preference for CTCF-anchored chromatin loops. Although the majority of CTCF occupancy is consistently maintained, we identified a specific set of binding sites enriched in the mouse-specific short interspersed element (SINE) family B2 that are restricted to the cleavage stages. Notably, we discovered that the neuroprotective protein ADNP counteracts the stable association of CTCF at SINE B2-derived CTCF-binding sites. Knockout of Adnp in the zygote led to impaired CTCF binding signal recovery, failed deposition of H3K9me3, and transcriptional derepression of SINE B2 during the morula-to-blastocyst transition, which further led to unfaithful cell differentiation in embryos around implantation. Our analysis highlights an ADNP-dependent restriction of CTCF binding during cell differentiation in preimplantation embryos. Furthermore, our findings shed light on the functional importance of transposable elements (TEs) in promoting genetic innovation and actively shaping the early embryo developmental process specific to mammals.

Natural killer cell-related anti-tumour adoptive cell immunotherapy.

Chimeric antigen receptor- (CAR-)modified T cells have been successfully used to treat blood cancer. With the improved research on anti-tumour adoptive cell therapy, researchers have focused on immune cells other than T lymphocytes. Natural killer (NK) cells have received widespread attention as barriers to natural immunity. Compared to T lymphocyte-related adoptive cell therapy, the use of NK cells to treat tumours does not cause graft-versus-host disease, significantly improving immunity. Moreover, NK cells have more sources than T cells, and the related modified cells are less expensive. NK cells function through several pathways in anti-tumour mechanisms. Currently, many anti-tumour clinical trials have used NK cell-related adoptive cell therapies. In this review, we have summarized the recent progress in NK cell-related adoptive cellular immunotherapy for tumour treatment and propose the current challenges faced by CAR-NK cell therapy.

Tunable Emission of Low-Dimensional Organic Metal Halides by Stoichiometric Ratio and Metal Center.

Low-dimensional (LD) organic metal halides (OMHs) have a bright future due to their excellent photoelectric characteristics and unique structure. However, the synthesis and emission control of LD-OMHs are still unclear. Herein, the different dimensional (zero-dimensional (0D), one-dimensional (1D), and three-dimensional (3D)) of OMHs were obtained by the reaction of 1,4-diazabicyclo (2.2.2) octane with PbBr2 in different stoichiometric ratios. This discovery shows that the structure and properties of OMHs can be regulated while maintaining the functional organic cations of OMHs, which broadens the path for the development of functional LD-OMHs. Among them, 0D-OMH 1 and 1D-OMH 3 have narrow-band (full width at half-maximum (fwhm) = 74 nm) and broad-band (fwhm = 201 nm) emission, respectively. We found that when organic cations have no contribution to the formation of conduction band minimum and valence band maximum, and the distances between polyhedrons are larger than the van der Waals diameter of the halogen atom, the effect of phonons on exciton transitions can be reduced to achieve a narrow-band emission. Further, Cu(I)- and Mn (II)-based 0D-OMHs were synthesized, which have high photoluminescence quantum yield (PLQY) (33.97 and 47.33%, respectively). When the emitting of 0D-OMHs produced by the interaction of the metal-center and halogens, the asymmetric planar metal-halogen structure will result in a higher PLQY.

Production of iron-enriched yeast and it's application in the treatment of iron-deficiency anemia.

Iron deficiency anemia (IDA) is one of the most serious forms of malnutrition. Wild type strains of Saccharomyces cerevisiae have higher tolerance to inorganic iron and higher iron conversion and accumulation capacity. The aim of this study was to investigate the effect of S. cerevisiae enriched iron as a potential organic iron supplement on mice with iron deficiency anemia. 60 male Kunming mice (KM mice, with strong adaptability and high reproduction rate, it can be widely used in pharmacology, toxicology, microbiology and other research) were randomly divided into normal control group and iron deficiency diet model group to establish IDA model. After the model was established, IDA mice were randomly divided into 5 groups: normal control group, IDA group, organic iron group (ferrous glycinate), inorganic iron group (ferrous sulfate) and S. cerevisiae enriched iron group. Mice in the experimental group were given different kinds of iron by intragastric administration once a day for 4w. The results showed that S. cerevisiae enriched iron had an effective recovery function, and the body weight and hematological parameters of IDA mice returned to normal levels. The activities of superoxide dismutase, glutathione peroxidase and total antioxidant capacity in serum were increased. In addition, the strain no. F8, able to grow in an iron-rich environment, was more effective in alleviating IDA and improving organ indices with fewer side effects compared to ferrous glycinate and ferrous sulfate groups. This study suggests that the iron-rich strain no. F8 may play an important role in improving IDA mice and may be developed as a new iron supplement.

Fluorescence modulation of quantum dots in subsurface defects of optical elements by a linearly polarized light.

The limited excitation efficiency of quantum dots in the detection of subsurface defects in optical elements by quantum dot fluorescence gives rise to insufficient accuracy. To enhance the excitation efficiency of quantum dots, we studied the modulation of the polarization direction of linearly polarized incident light on quantum dot fluorescence. We first apply density matrix evolution theory to study the quantum dots interacting with linearly polarized incident light and emitting fluorescence. The fluorescence intensity exhibits cosine oscillations versus modulated laser polarization. It reaches a maximum value at the polarization angle zero, and then decreases as the angle becomes larger until π/2. The experimental results for the quantum dot in both solutions and subsurface defect of optical elements confirmed these results. For optical elements tagged with CdSe/ZnS quantum dots, the fluorescence intensity increases by 61.7%, and the area for the detected subsurface defects increases by 142.9%. Similarly, for C and InP/ZnS quantum dots, there are also increases in both the fluorescence intensity and the area of subsurface defects. Our study suggests that the subsurface defect detection in optical elements by the linearly polarized incident light could enhance the detection accuracy of subsurface defects in optical elements, and potentially achieve super-resolution imaging of subsurface defects.

Design and control of a fast steering mirror based on flexible supports and piezoelectric ceramic actuators.

The use of the fast steering mirror in an optical path requires strict volume control, and traditional structures have low space-utilization efficiency, resulting in traditional actuators having limited output in narrow spaces. The design in this paper adopts a combination of flexible universal supports and piezoelectric ceramic actuators, greatly reducing the layout space of the rotating-shaft system. We accurately model the design structure and develop closed-loop control methods to further improve the closed-loop control accuracy of the system. The experimental results indicate that the developed control method effectively improves the response speed and bandwidth and thus has good potential for use in engineering applications.

PROTACs in Epigenetic Cancer Therapy: Current Status and Future Opportunities.

The epigenetic regulation of gene functions has been proven to be strongly associated with the development and progression of cancer. Reprogramming the cancer epigenome landscape is one of the most promising target therapies in both treatments and in reversing drug resistance. Proteolytic targeted chimeras (PROTACs) are an emerging therapeutic modality for selective degradation via the native ubiquitin-proteasome system. Rapid advances in PROTACs have facilitated the exploration of targeting epigenetic proteins, a lot of PROTAC degraders have already been designed in the field of epigenetic cancer therapy, and PROTACs targeting epigenetic proteins can better exploit target druggability and improve the mechanistic understanding of the epigenetic regulation of cancer. Thus, this review focuses on the progress made in the development of PROTAC degraders and PROTAC drugs targeting epigenetics in cancer and discusses challenges and future opportunities for the field.

Conjugated sulfonamides as a class of organic lithium-ion positive electrodes.

The applicability of organic battery materials in conventional rocking-chair lithium (Li)-ion cells remains deeply challenged by the lack of Li-containing and air-stable organic positive electrode chemistries. Decades of experimental and theoretical research in the field has resulted in only a few recent examples of Li-reservoir materials, all of which rely on the archetypal conjugated carbonyl redox chemistry. Here we extend the chemical space of organic Li-ion positive electrode materials with a class of conjugated sulfonamides (CSAs) and show that the electron delocalization on the sulfonyl groups endows the resulting CSAs with intrinsic oxidation and hydrolysis resistance when handled in ambient air, and yet display reversible electrochemistry for charge storage. The formal redox potential of the uncovered CSA chemistries spans a wide range between 2.85 V and 3.45 V (versus Li+/Li0), finely tunable through electrostatic or inductive molecular design. This class of organic Li-ion positive electrode materials challenges the realm of the inorganic battery cathode, as this first generation of CSA chemistries already displays gravimetric energy storage metrics comparable to those of the stereotypical LiFePO4.

Liquid crystal spatial light modulator based non-mechanical beam steering system fractional-order model.

The liquid crystal spatial light modulator (LCSLM) is an optical device that can realise non-mechanical beam scanning. However, the traditional integer-order model cannot adequately characterise the dynamic performance of LCSLM beam steering because of the viscoelasticity of liquid crystals. This paper uses the memory characteristics of fractional calculus to construct a fractional constitutive equation for liquid crystals. Combining this equation with the LCSLM beam steering principle, a fractional-order model of the beam steering system is established, and the Legendre wavelet integration operational matrix method is used to estimate the model parameters. In addition, we established a test platform for the dynamic characteristics of LCSLM beam steering system and verified the effectiveness of the established model through experiments. The fitting effects of the integer-order and fractional-order models are compared, and the influence of different model orders on the dynamic performance of beam steering is analysed. Experimental results show that the fractional-order model can accurately describe the dynamic process of beam steering, and this model can be applied to the study of LCSLM-based two-dimensional non-mechanical beam steering control strategies to achieve fast, accurate, and stable beam scanning.

Diffraction characteristics of a non-mechanical beam steering system with liquid crystal polarization gratings.

The non-mechanical beam steering system is composed of multiple liquid crystal polarization gratings (LCPGs) cascaded by binary or ternary technologies. However, cascading multiple LCPGs cause the beam from one LCPG to obliquely enter the subsequent LCPGs, changing their diffraction efficiency and working voltage at different steering angles. This paper uses the elastic continuum theory of liquid crystals to simulate the tilt angle of liquid crystal molecules under different voltages. The transmission process of the beam in the system at oblique incidence is described with an extended Jones matrix, and the highest diffraction efficiency and working voltage of each LCPG at different steering angles are calculated using vector diffraction theory. It is convenient to calibrate the LCPGs' working voltage and analyze the system's diffraction characteristics. In addition, we used an improved binary cascade technology to design a LCPG non-mechanical beam steering system with a steering angle of ±10° and an angular resolution of 0.67°. Compared with binary cascade, this technology can effectively reduce the number of cascaded devices and increase the system throughput under the same maximum beam steering angle and angular resolution.

Heterologous expression of pediocin/papA in Bacillus subtilis.

Listeria monocytogenes is a food-borne pathogen. Pediocin is a group IIα bacteriocin with anti-listeria activity that is naturally produced by Pediococcus acidilactic and Lactobacillus plantarum. The pedA/papA gene encodes pediocin/plantaricin. In native hosts, the expression and secretion of active PedA/PapA protein rely on the accessory protein PedC/PapC and ABC transporter PedD/PapD on the same operon. The excretion machines were also necessary for pediocin protein expression in heterologous hosts of E. coli, Lactobacillus lactis, and Corynebacterium glutamicum. In this study, two vectors carrying the codon sequence of the mature PapA peptide were constructed, one with and one without a His tag. Both fragments were inserted into the plasmid pHT43 and transformed into Bacillus subtilis WB800N. The strains were induced with IPTG to secrete the fused proteins PA1 and PA2. Supernatants from both recombinant strains can inhibit Listeria monocytogenes ATCC54003 directly. The fused protein possesses inhibition activity as a whole dispense with removal of the leading peptide. This is the first report of active pediocin/PapA expression without the assistance of PedCD/PapCD in heterogeneous hosts. In addition, the PA1 protein can be purified by nickel-nitrilotriacetic acid (Ni-NTA) metal affinity chromatography.

Synthesis and fungicidal activity of methyl (E)-1-(2-((E)-2-methoxy-1-(methoxyimino)-2-oxoethyl)benzyl)-2-(1-arylidene)hydrazine-1-carboxylates †‡.

To discover novel strobilurin fungicides, a series of methyl (E)-1-(2-((E)-2-methoxy-1-(methoxy-imino)-2-oxoethyl)benzyl)-2-(1-arylidene)hydrazine-1-carboxylates were designed based on the principle of biologically active splicing and the receptor target structure. The fungicidal activity results show that this class of compounds has excellent fungicidal activity, especially against S. sclerotiorum (Lib.) deBary, wheat white powder and puccinia polysora. The result of structure-activity relationship implied that the introduction of t-butyl in the side chain facilitates the hydrophobic interaction between the compound and the active site. The electrostatic effect of the substituents on the benzene ring is also a key factor affecting such activities. Among them, the compound I-1 not only showed a fungicidal effect comparable to that of kresoxim-methyl in vivo, but also had an excellent inhibitory effect on spore germination of P. oryzae Cav in vitro, which indicated that it could be used as a potential commercial fungicide for plant disease control.

Three-dimensional point cloud denoising via a gravitational feature function.

Point cloud noise is inevitable in the LiDAR scanning of objects and affects measurement accuracy and integrity. To minimize such noise, we propose a gravitational feature function-based point cloud denoising algorithm and a universal gravitation formula for a point cloud. First, we calculate the point cloud barycenter (i.e., the position of the average mass distribution) and the spherical neighborhood of points in terms of the distribution of the point cloud in three-dimensional space. Next, using the proposed formula, we calculate the gravitational forces between the barycenter and the spherical neighborhood of all points. We then combine all of the gravitational forces into a gravitational feature function and filter the noises in the point cloud using a gravitational feature-function threshold. This novel algorithm, to the best of our knowledge, effectively removes drift noises and takes into account the local and global structure of point clouds. Finally, we demonstrate the effectiveness of the algorithm through extensive experiments in which sparse, dense, and mixed noises are removed.

High-efficiency chromosomal integrative amplification strategy for overexpressing α-amylase in Bacillus licheniformis.

Bacillus licheniformis is a well-known platform strain for production of industrial enzymes. However, the development of genetically stable recombinant B. licheniformis for high-yield enzyme production is still laborious. Here, a pair of plasmids, pUB-MazF and pUB'-EX1, were firstly constructed. pUB-MazF is a thermosensitive, self-replicable plasmid. It was able to efficiently cure from the host cell through induced expression of an endoribonuclease MazF, which is lethal to the host cell. pUB'-EX1 is a nonreplicative and integrative plasmid. Its replication was dependent on the thermosensitive replicase produced by pUB-MazF. Transformation of pUB'-EX1 into the B. licheniformis BL-UBM harboring pUB-MazF resulted in both plasmids coexisting in the host cell. At an elevated temperature, and in the presence of isopropyl-1-thio-ß-d-galactopyranoside and kanamycin, curing of the pUB-MazF and multiple-copy integration of pUB'-EX1 occurred, simultaneously. Through this procedure, genetically stable recombinants integrated multiple copies of amyS, from Geobacillus stearothermophilus ATCC 31195 were facilely obtained. The genetic stability of the recombinants was verified by repeated subculturing and shaking flask fermentations. The production of α-amylase by recombinant BLiS-002, harboring five copies of amyS, in a 50-l bioreactor reached 50 753 U/ml after 72 hr fermentation. This strategy therefore has potential for production of other enzymes in B. licheniformis and for genetic modification of other Bacillus species.

Changes in the composition of the soil seed bank of grassland after giant ragweed (Ambrosia trifida L.) invasion.

Giant ragweed (Ambrosia trifida L.), an invasive weed, has an expanding distribution area and has recently started to spread in grasslands. This unusual event threatens grasslands worldwide. In this study, we aimed to evaluate the changes in the grassland soil seed banks caused by the giant ragweed invasion in Yili Valley, Xinjiang, China. Using the space-for-time substitution approach, we compared and quantified the soil seed bank communities in a grassland over eight years following giant ragweed invasion and after its removal. The results showed that the duration of invasion determined whether giant ragweed might pose a significant threat to the native seed bank community. Four years after the invasion, the in-site seed bank density of native community significantly decreased (30.44%), while the relative coverage of giant ragweed aboveground reached 83.75%. Furthermore, the species richness in the seed bank decreased significantly (12.36%), while the relative coverage of giant ragweed reached 100% six years after the invasion. Eight years after the invasion, the seed bank density and species richness of the native community decreased by 83.28% and 39.33%, respectively, whereby the seed banks tended to be homogeneous. After the removal of giant ragweed, the potential for regeneration was limited by the residual seed bank densities of the native community. Although the native seed bank density had increased significantly after three years of restoration, new growth was dominated by weedy species, rather than by the distinctive components of the grassland habitat. Our study clarifies the process by which giant ragweed causes damage to grasslands and serves as a reference for grassland restoration and management efforts.

Angiocrine FSTL1 (Follistatin-Like Protein 1) Insufficiency Leads to Atrial and Venous Wall Fibrosis via SMAD3 Activation.

OBJECTIVE: Angiocrine factors, mediating the endothelial-mural cell interaction in vascular wall construction as well as maintenance, are incompletely characterized. This study aims to investigate the role of endothelial cell-derived FSTL1 (follistatin-like protein 1) in vascular homeostasis. Approach and Results: Using conditional knockout mouse models, we show that loss of FSTL1 in endothelial cells (Fstl1ECKO) led to an increase of pulmonary vascular resistance, resulting in the heart regurgitation especially with tricuspid valves. However, this abnormality was not detected in mutant mice with Fstl1 knockout in smooth muscle cells or hematopoietic cells. We further showed that there was excessive αSMA (α-smooth muscle actin) associated with atrial endocardia, heart valves, veins, and microvessels after the endothelial FSTL1 deletion. There was also an increase in collagen deposition, as demonstrated in livers of Fstl1ECKO mutants. The SMAD3 (mothers against decapentaplegic homolog 3) phosphorylation (pSMAD3) was significantly enhanced, and pSMAD3 staining was colocalized with αSMA in vein walls, suggesting the activation of TGFß (transforming growth factor ß) signaling in vascular mural cells of Fstl1ECKO mice. Consistently, treatment with a TGFß pathway inhibitor reduced the abnormal association of αSMA with the atria and blood vessels in Fstl1ECKO mutant mice. CONCLUSIONS: The findings imply that endothelial FSTL1 is critical for the homeostasis of vascular walls, and its insufficiency may favor cardiovascular fibrosis leading to heart failure.

Analysis of the etiologies of female infertility in Yunnan minority areas.

BACKGROUND: The present study aims to provide a comparative analysis of the etiologies of female infertility between Dehong, on the Yunnan Frontier, and Kunming. METHODS: A retrospective study, which included 941 infertile females in Kunming who were treated in the First People's Hospital of Yunnan Province and infertile females who were treated in the local hospital in Dehong from January 2016 to November 2018, was conducted. A comparative analysis of the etiologies of infertility in the two regions was then carried out. RESULTS: In patients with primary infertility, ovulation disorder (15.03%) was the main cause of infertility in Kunming, and pelvic inflammatory disease (25.59%) was the main cause in Dehong. With regard to secondary infertility, although pelvic inflammatory disease was the main cause of infertility in both regions, the incidence of intrauterine adhesions in Kunming was significantly higher than in Dehong. CONCLUSIONS: The etiology of infertility showed different epidemiological characteristics depending on the region, hence individualized treatment should be given accordingly.

Structure Analysis and Study of Biological Activities of Condensed Tannins from Bruguiera gymnorhiza (L.) Lam and Their Effect on Fresh-Cut Lotus Roots.

Bruguiera gymnorhiza (L.) Lam is a mangrove plant that spread in many parts of the world. Though mangrove plant polyphenols have been reported to exhibit many biological activities, little is known about mangrove plant tannins. To explore the application value of tannins from B. gymnorhiza, analyses on the structure and biological activity of condensed tannins (CTs) from Bruguiera gymnorhiza (L.) Lam were carried out. The results from 13C nuclear magnetic resonance (13C-NMR) and reversed-phase, high-performance liquid chromatography (RP-HPLC) showed that the CTs were dominated by procyanidins, with a small quantity of prodelphinidins and propelargonidins; and that the monomeric constituents of B. gymnorhiza tannins were catechin/epicatechin, gallocatechin/epigallocatechin and afzelechin/epiafzelechin. The CTs were reversible and mixed competitive inhibitors of tyrosinase and the 50% inhibiting concentration (IC50) was estimated to be 123.90 ± 0.140 µg/mL. The antioxidant activities of CTs from B. gymnorhiza leaves were evaluated, the IC50 for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid diammonium salt) (ABTS) scavenging activities were 88.81 ± 0.135 and 105.03 ± 0.130 µg/mL, respectively, and the ferric ion reducing antioxidant power (FRAP) value was 1052.27 ± 4.17 mgAAE/g. In addition, the results from fresh-keeping assays on fresh-cut lotus root reveal that CTs from B. gymnorhiza had excellent effects on inhibiting the activities of polyphenol oxidase (PPO) and peroxidase (POD), protecting fresh-cut lotus root from the oxidation of total phenolics and malondialdehyde (MDA) content and slowing the increase in total phenol content (TPC) at 4 °C during the whole storage period. Therefore, CTs showed good effects against the browning of fresh-cut lotus root. Together, these results suggested that B. gymnorhiza CTs are promising antibrowning agents for fresh-cut fruits.

Evaluation of ibuprofen contamination in local urban rivers and its effects on immune parameters of juvenile grass carp.

Ibuprofen as a non-steroidal anti-inflammatory drug can be detected in the aquatic environments all over the world. This study evaluated the effects of ibuprofen on the immune parameters of juvenile grass carp at the concentration in real environments which were determined by detecting its concentrations in the surface water of local rivers. The concentration of ibuprofen ranged from 13.2 to 95.5 ng/L with a mean value of 47.9 ng/L in the surface water of local rivers detected by solid-phase extraction followed by LC-MS/MS analysis. Accordingly, juvenile grass carp were exposed to 4.8, 48.0 and 480.0 ng/L of ibuprofen for 14 days. The serum lysozyme activity of these fish decreased, while the serum creatinine levels were not affected after the exposure. Moreover, the mRNA expression of interleukin 6 in the skin and interleukin 1 beta and tumor necrosis factor alpha in the gills was enhanced by this exposure. These results collectively suggest that ibuprofen at environmentally relevant concentration can affect the immune parameters of juvenile grass carp, providing an insight into the possibility of this contaminant to modify the immunostatus of fish.

Ubiquitin-specific protease 19 blunts pathological cardiac hypertrophy via inhibition of the TAK1-dependent pathway.

Ubiquitin-specific protease 19 (USP19) belongs to USP family and is involved in promoting skeletal muscle atrophy. Although USP19 is expressed in the heart, the role of USP19 in the heart disease remains unknown. The present study provides in vivo and in vitro data to reveal the role of USP19 in preventing pathological cardiac hypertrophy. We generated USP19-knockout mice and isolated neonatal rat cardiomyocytes (NRCMs) that overexpressed or were deficient in USP19 to investigate the effect of USP19 on transverse aortic constriction (TAC) or phenylephrine (PE)-mediated cardiac hypertrophy. Echocardiography, pathological and molecular analysis were used to determine the extent of cardiac hypertrophy, fibrosis, dysfunction and inflammation. USP19 expression was markedly increased in rodent hypertrophic heart or cardiomyocytes underwent TAC or PE culturing, the increase was mediated by the reduction of Seven In Absentia Homolog-2. The extent of TAC-induced cardiac hypertrophy, fibrosis, dysfunction and inflammation in USP19-knockout mice was exacerbated. Consistently, gain-of-function and loss-of-function approaches that involved USP19 in cardiomyocytes suggested that the down-regulation of USP19 promoted the hypertrophic phenotype, while the up-regulation of USP19 improved the worsened phenotype. Mechanistically, the USP19-elicited cardiac hypertrophy improvement was attributed to the abrogation of the transforming growth factor beta-activated kinase 1 (TAK1)-p38/JNK1/2 transduction. Furthermore, the inhibition of TAK1 abolished the aggravated hypertrophy induced by the loss of USP19. In conclusion, the present study revealed that USP19 and the downstream of TAK1-p38/JNK1/2 signalling pathway might be a potential target to attenuate pathological cardiac hypertrophy.