Smurf1-targeting microRNA-136-5p-modified bone marrow mesenchymal stem cells combined with 3D-printed ß-tricalcium phosphate scaffolds strengthen osteogenic activity and alleviate bone defects.

Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR-136-5p or Smurf1 expression were transfected into BMSCs. The effects of miR-136-5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR-136-5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR-136-5p/BMSCs/ß-TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro-CT and HE staining. Elevating miR-136-5p-3p or suppressing Smurf1 could stimulate OD of BMSCs. miR-136-5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR-136-5p on the OD of BMSCs. miR-136-5p/BMSCs/ß-TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1-targeting miR-136-5p-modified BMSCs combined with 3D-printed ß-TCP scaffolds can strengthen osteogenic activity and alleviate bone defects.

Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD.

Highly contagious respiratory illnesses like influenza and COVID-19 pose serious risks to public health. A two-in-one vaccine would be ideal to avoid multiple vaccinations for these diseases. Here, we generated a chimeric receptor binding domain of the spike protein (S-RBD) and hemagglutinin (HA)-stalk-based vaccine for both SARS-CoV-2 and influenza viruses. The S-RBD from SARS-CoV-2 Delta was fused to the headless HA from H1N1 (H1Delta), creating a chimera that forms trimers in solution. The cryo-electron microscopy structure of the chimeric protein complexed with the RBD-targeting CB6 and the HA-stalk-targeting CR9114 antibodies shows that the trimeric protein is stable and accessible for neutralizing antibody binding. Immunization with the vaccine elicited high and long-lasting neutralizing antibodies and effectively protected mice against the challenges of lethal H1N1 or heterosubtypic H5N8, as well as the SARS-CoV-2 Delta or Omicron BA.2 variants. Overall, this study offers a two-in-one universal vaccine design to combat infections caused by both SARS-CoV-2 variants of concern and influenza viruses.

Risk-Taking Behavior Among Male Adolescents: The Role of Observer Presence and Individual Self-Control.

A number of studies have focused on the same-sex peer effect on and the developmental difference in adolescent risk-taking in terms of the dual systems model. Little research, however, addresses the effects of different observers, the role of different levels of individual self-control, and their interactions. To fill this gap, the present study examined the main and interactive effects of observer presence and individual self-control on male adolescents' risk-taking behavior with an experimental design. A total of 261 male adolescents (Mage = 15.79 ± 0.79, range = 14-18) completed an adapted Stoplight Task, which measures risk-taking behavior, in the presence of an observer, either peer or adult, either male or female. The results indicated that a same-sex peer's presence and low self-control were both risk factors of male adolescents' risk-taking, but did only low self-control male adolescents take serious risks when in the presence of a same-sex peer whereas those with high self-control consistently had low levels of risk-taking under any condition. An opposite-sex observer, particularly an opposite-sex adult's presence, played a similar protective role for male adolescents with low self-control. The findings suggest that a high level of self-control closely related to the cognitive control system may significantly buffer the negative effect of an adverse social stimulus which activates the social-emotional system on male adolescents' risk-taking; the findings also reveal that an opposite-sex adult's presence may contribute to a decrease in male adolescents' risk-taking by improving their cognitive control system.

Myricetin Restores Aß-Induced Mitochondrial Impairments in N2a-SW Cells.

Alzheimer's disease (AD) is the most common type of dementia that occurs in the elderly. Amyloid hypothesis is one of the most studied pathological mechanisms, and ß-amyloid (Aß) is the drug target for most clinical trials. Mitochondrial dysfunction induced by the Aß-precursor protein (APP)/Aß has been suggested to play a key role in the development of AD. Here, we explored the effects of myricetin, a polyphenol compound abundant in fruits and vegetables, on mitochondrial damages in N2a-SW cells. After the treatment of myricetin, mitochondrial depolarization was improved by increasing the mitochondrial membrane potential. Mitochondrial biogenesis as well as mitochondrial genome integrity was enhanced via increased levels of PGC-1α, Nrf1, TFAM, and the copy number of mtDNA. Mitochondrial functions were restored as represented by the increased levels of proteins involved in the electron transport chain and the adenosine 5'-triphosphate (ATP) content and the decreased concentration of ROS. Mitochondrial dynamics and mitophagy were ameliorated through the regulation of proteins involved in fusion (OPA1 and Mfn2), fission (Drp1 and Fis1), and mitophagy (PINK1 and Parkin). Thus, it is summarized that myricetin could recover the mitochondrial impairments in N2a-SW cells, exhibiting the potential to promote neuroprotection for APP/Aß-related diseases, including AD.

A Flexible, Fireproof, Composite Polymer Electrolyte Reinforced by Electrospun Polyimide for Room-Temperature Solid-State Batteries.

Solid-state batteries (SSBs) have attracted considerable attention for high-energy-density and high-safety energy storage devices. Many efforts have focused on the thin solid-state-electrolyte (SSE) films with high room-temperature ionic conductivity, flexibility, and mechanical strength. Here, we report a composite polymer electrolyte (CPE) reinforced by electrospun PI nanofiber film, combining with succinonitrile-based solid composite electrolyte. In situ photo-polymerization method is used for the preparation of the CPE. This CPE, with a thickness around 32.5 µm, shows a high ionic conductivity of 2.64 × 10-4 S cm-1 at room temperature. It is also fireproof and mechanically strong, showing great promise for an SSB device with high energy density and high safety.

Robust and high thermal-stable composite polymer electrolyte reinforced by PI nanofiber network.

To address the flammable and chemical unstable problems of liquid electrolyte, the solid electrolyte is a promising candidate to replace liquid electrolyte for solid-state batteries. Herein, a composite polymer electrolyte (CPE) of 3D polyimide (PI)-nanofiber membrane-incorporated polyethylene oxide (PEO)/lithium bis (triflu-romethanesulphonyl) imid (LiTFSI) is reported. Three advantages of the PI nanofiber network in the CPE include providing a continuous, rapid transport channel of lithium ions to improve the Li-ion conductivity, improving the mechanical properties and stability, and effectively inhibiting the dendrite growth of Li metal. The PI/PEO/LiTFSI CPE delivers an ionic conductivity of 4.2 × 10-4S cm-1at 60 °C, a wider electrochemical window to 5.4 V, and an excellent thermal stability, which result in the excellent electrochemical performance of LiFePO4full cells assembled with PI/PEO/LiTFSI CPE.

Seaweed polysaccharide mitigates intestinal barrier dysfunction induced by enterotoxigenic Escherichia coli through NF-κB pathway suppression in porcine intestinal epithelial cells.

This study aimed to investigate the protective effects and underlying mechanism of seaweed polysaccharide (SWP) on intestinal epithelial barrier dysfunction induced by E. coli in an IPEC-J2 model. A preliminary study was done to screen optimum SWP concentrations by cell viability, cytotoxicity, apoptosis and proliferation evaluation. The regular study was conducted to evaluate the protective effects of SWP against E. coli challenge via the analysis of transepithelial electrical resistance (TEER), tight junction proteins, NF-κB signalling pathway, proinflammatory cytokines and the E. coli adhesion and invasion. Our results show that 4 h E. coli challenge down-regulated tight junction proteins expression, decreased TEER, activated NF-κB signalling pathway and increased proinflammatory response, which indicates that the E. coli infection model was well-established. Pre-treatment with 240 µg/ml SWP for 24 h alleviated the 4 h E. coli -induced intestinal epithelial barrier dysfunction, as evidenced by the up-regulated expression of Occludin, Claudin-1 and ZO-1 at both mRNA and protein level and the increased TEER of IPEC-J2 cells. Pre-incubation with 240 µg/ml SWP for 24 h inhibited the activation of the NF-κB signalling pathway by 4 h E. coli challenge, including the decreased mRNA expression of TLR-4, MyD88, IκBα, p-65, as well as the reduced ratio of protein expression of p-p65/p65. Also, pre-treatment with 240 µg/ml SWP for 24 h decreased proinflammatory response (IL-6 and TNF-α) induced by 4 h E. coli challenge and decreased the E. coli adhesion and invasion. In conclusion, SWP mitigated intestinal barrier dysfunction caused by E. coli through NF-κB pathway in IPEC-J2 cells and 240 µg/ml SWP exhibited better effect. Our results also provide a fundamental basis for SWP in reducing post-weaning diarrhoea of weaned piglets, especially under E. coli -infected or in-feed antibiotic-free conditions.

Fisetin inhibits tau aggregation by interacting with the protein and preventing the formation of ß-strands.

Alzheimer's disease is a neurodegenerative disease which severely impacts the health of the elderly. Current treatments are only able to alleviate symptoms, but not prevent or cure the disease. The neurofibrillary tangles formed by tau protein aggregation are one of the defining characteristics of Alzheimer's disease, so tau protein has become a key target for the drug design. In this study, we show that fisetin, a plant-derived polyphenol compound, can inhibit aggregation of the tau fragment, K18, and can disaggregate tau K18 filaments in vitro. Meanwhile it is able to prevent the formation of tau aggregates in cells. Both experimental and computational studies indicate that fisetin could directly interact with tau K18 protein. The binding is mainly created by hydrogen bond and van der Waal force, prevents the formation of ß-strands at the two hexapeptide motifs, and does not perturb the secondary structure or the tubulin binding ability of tau protein. In summary, fisetin might be a candidate for further development as a potential preventive or therapeutic drug for Alzheimer's disease.

UNG2 deacetylation confers cancer cell resistance to hydrogen peroxide-induced cytotoxicity.

Cancer therapeutics produce reactive oxygen species (ROS) that damage the cancer genome and lead to cell death. However, cancer cells can resist ROS-induced cytotoxicity and survive. We show that nuclear-localized uracil-DNA N-glycosylase isoform 2 (UNG2) has a critical role in preventing ROS-induced DNA damage and enabling cancer-cell resistance. Under physiological conditions, UNG2 is targeted for rapid degradation via an interaction with the E3 ligase UHRF1. In response to ROS, however, UNG2 protein in cancer cells exhibits a remarkably extended half-life. Upon ROS exposure, UNG2 is deacetylated at lysine 78 by histone deacetylases, which prevents the UNG2-UHRF1 interaction. Accumulated UNG2 protein can thus excise the base damaged by ROS and enable the cell to survive these otherwise toxic conditions. Consequently, combining HDAC inhibitors (to permit UNG2 degradation) with genotoxic agents (to produce cytotoxic cellular levels of ROS) leads to a robust synergistic killing effect in cancer cells in vitro. Altogether, these data support the application of a novel approach to cancer treatment based on promoting UNG2 degradation by altering its acetylation status using an HDAC inhibitor.

SIRT7 activates p53 by enhancing PCAF-mediated MDM2 degradation to arrest the cell cycle.

Sirtuin 7 (SIRT7), an NAD+-dependent deacetylase, plays vital roles in energy sensing, but the underlying mechanisms of action remain less clear. Here, we report that SIRT7 is required for p53-dependent cell-cycle arrest during glucose deprivation. We show that SIRT7 directly interacts with p300/CBP-associated factor (PCAF) and the affinity for this interaction increases during glucose deprivation. Upon binding, SIRT7 deacetylates PCAF at lysine 720 (K720), which augments PCAF binding to murine double minute (MDM2), the p53 E3 ubiquitin ligase, leading to accelerated MDM2 degradation. This effect results in upregulated expression of the cell-cycle inhibitor, p21Waf1/Cip1, which further leads to cell-cycle arrest and decreased cell viability. These data highlight the importance of the SIRT7-PCAF interaction in regulating p53 activity and cell-cycle progression during conditions of glucose deprivation. This axis may represent a new avenue to design effective therapeutics based on tumor starvation.

Dietary guanidinoacetic acid improves the growth performance and skeletal muscle development of finishing pigs through changing myogenic gene expression and myofibre characteristics.

This study aimed to evaluate the effects of dietary guanidine acetic acid (GAA) supplementation on growth performance, carcass traits and the expression of muscle growth-related genes in finishing pigs. A total of 128 (81.03 ± 1.09 kg body weight) crossbred pigs (Duroc × Landrace ×Yorkshire) were blocked by body weight and allotted to 16 pens (eight pigs per pen), and pens were randomly assigned within blocks to one of five dietary treatments, with a basal diet (control group) or a basal diet supplemented with 0.03%, 0.06% and 0.09% GAA respectively. During the 60-day trial, GAA increased the average dairy gain (ADG) and average daily feed intake (ADFI) (p < .05). The back fat thickness of pigs fed 0.06% GAA was lower than other groups (p < .05). Pigs fed 0.06% GAA had improved lean meat percentage, loin muscle area, shear force and cross-sectional area of muscle fibre in comparison with control group (p < .05). The drop loss and the muscle fibre density in pigs fed 0.06% GAA were lower than control (p < .05). In addition, dietary GAA enhanced the expression of myosin heavy chain gene (MYH4), myogenic determination (Myod) and myogenic factor 5 (Myf5) in longissimus dorsi and carnitine palmitoyltransferase-1(CPT-1) in liver (p < .05). Meanwhile, GAA decreased the expression of Myostatin in longissimus dorsi and fatty acid synthase (FAS) in liver (p < .05). In conclusion, our results showed that appropriate dietary GAA supplementation (0.06%) promotes skeletal muscle development through changing myogenic gene expression and myofibre characteristics.

Two new species of the genus Trachylophus Gahan, 1888 (Coleoptera, Cerambycinae, Cerambycini) from China.

Two new species of the genus Trachylophus Gahan, 1888, T. tianmuensis sp. nov. and T. chiangi sp. nov. from China are described. The adult habitus and male genitalia of the two new species are described in detail.

Pointing error analysis of Risley-prism-based beam steering system.

Based on the vector form Snell's law, ray tracing is performed to quantify the pointing errors of Risley-prism-based beam steering systems, induced by component errors, prism orientation errors, and assembly errors. Case examples are given to elucidate the pointing error distributions in the field of regard and evaluate the allowances of the error sources for a given pointing accuracy. It is found that the assembly errors of the second prism will result in more remarkable pointing errors in contrast with the first one. The pointing errors induced by prism tilt depend on the tilt direction. The allowances of bearing tilt and prism tilt are almost identical if the same pointing accuracy is planned. All conclusions can provide a theoretical foundation for practical works.

Frame frequency prediction for Risley-prism-based imaging laser radar.

A dual-wedge scanner has potential applications in laser imaging radar. To realize fast scanning imaging without a blind region, the rotation rates of the wedges have to be controlled to perform beam scanning along appropriate track paths. The first-order paraxial approximation method is employed to investigate the 2D scan patterns and path density for different angular frequency ratios of the wedges rotating steadily in the same and opposite directions. The frame rate of no-blind-region scanning imaging is estimated in terms of the imaging coverage requirement. The internal relations between the rotation rates, the instantaneous field of view (IFOV), and the imaging velocity are revealed. The results show that the spiral scanning trace, resulting from co-rotating wedges, is dense in the center and sparse at the edge of the scanning field. The reverse results can be obtained for the rosette scanning trace, resulting from counter-rotating wedges. The denser the scanning trace is, the longer the scan period is. The faster the wedges rotate and the wider the IFOV is, the higher the frame rate is. When the ratio of the width of IFOV to the angular radius of the scanning field is 0.15, the frame rate of no-blind-region spiral scanning imaging can be up to 18 fps for wedge rotation rate of 12000 r/min, and that for rosette scanning imaging can be up to 20 fps.

Motion control of the wedge prisms in Risley-prism-based beam steering system for precise target tracking.

Two exact inverse solutions of Risley prisms have been given by previous authors, based on which we calculate the gradients of the scan field that open a way to investigate the nonlinear relationship between the slewing rate of the beam and the required angular velocities of the two wedge prisms in the Risley-prism-based beam steering system for target tracking. The limited regions and singularity point at the center and the edge of the field of regard are discussed. It is found that the maximum required rotational velocities of the two prisms for target tracking are nearly the same and are dependent on the altitude angle. The central limited region is almost independent of the prism parameters. The control singularity at the crossing center path can be avoided by switching the two solutions.

Theoretical and experimental determination of steering mechanism for Risley prism systems.

Two different analytical methods, the first-order paraxial approximation method and the nonparaxial ray tracing method, are applied to determine the steering mechanism of the Risley prism system, including the pointing prediction and the complete and exact inverse orientation solutions. The analytical results obtained with the two different methods are investigated in detail about the pointing prediction and the two groups of inverse orientation solutions, respectively. Risley prism equipment for wide angular range beam scanning is assembled and the experimental setup is built to test the steering mechanism of the Risley prism system. Experimental results validate the availability of the nonparaxial ray tracing method to discuss the beam steering mechanism for the Risley prism system.

A multivalent three-point linkage analysis model of autotetraploids.

Because of its widespread occurrence and role in shaping evolutionary processes in the biological kingdom, especially in plants, polyploidy has been increasingly studied from cytological to molecular levels. By inferring gene order, gene distances and gene homology, linkage mapping with molecular markers has proven powerful for investigating genome structure and organization. Here we review and assess a general statistical model for three-point linkage analysis in autotetraploids by integrating double reduction, a phenomenon that commonly occurs in autopolyploids whose chromosomes are derived from a single ancestral species. This model does not require any assumption on the distribution of the occurrence of double reduction and can handle the complexity of multilocus linkage in terms of crossover interference. Implemented with the expectation-maximization (EM) algorithms, the model can estimate and test the recombination fractions between less informative dominant markers, thus facilitating its practical implications for any autopolyploids in most of which inexpensive dominant markers are still used for their genetic and evolutionary studies. The model was applied to reanalyze a published data in tetraploid switchgrass, validating its practical usefulness and utilization.