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Photodynamic therapy (PDT) under hypoxic conditions and drug resistance in chemotherapy are perplexing problems in anti‐tumor treatment. In addition, central nervous system neoplasm‐targeted nanoplatforms are urgently required. To address these issues, a new multi‐functional protein hybrid nanoplatform is designed, consisting of transferrin (TFR) as the multicategory solid tumor recognizer and hemoglobin for oxygen supply (ODP‐TH). This protein hybrid framework encapsulates the photosensitizer protoporphyrin IX (PpIX) and chemotherapeutic agent doxorubicin (Dox), which are attached by a glutathione‐responsive disulfide bond. Mechanistically, ODP‐TH crosses the blood–brain barrier (BBB) and specifically aggregated in hypoxic tumors via protein homology recognition. Oxygen and encapsulated drugs ultimately promote a therapeutic effect by down‐regulating the abundance of multidrug resistance gene 1 (MDR1) and hypoxia‐inducible factor‐1‐α (HIF‐1α). The results reveal that ODP‐TH achieves oxygen transport and protein homology recognition in the hypoxic tumor occupation. Indeed, compared with traditional photodynamic chemotherapy, ODP‐TH achieves a more efficient tumor‐inhibiting effect. This study not only overcomes the hypoxia‐related inhibition in combination therapy by targeted oxygen transport but also achieves an effective treatment of multiple tumors, such as breast cancer and glioma, providing a new concept for the construction of a promising multi‐functional targeted and intensive anti‐tumor nanoplatform. A new multi‐functional protein hybrid nanoplatform is designed, consisting of transferrin as the multicategory solid tumor recognizer and hemoglobin for oxygen supply. This study not only overcomes the hypoxia‐related inhibition in combination therapy by targeted oxygen transport but also achieves effective treatment of multiple tumors, providing a new concept for the construction of a promising multi‐functional targeted anti‐tumor nanoplatform.

Mastitis caused by Staphylococcus aureus infection not only causes serious economic losses, but also affects human health. Se plays an important role in body immunity. However, the mechanisms by which Se regulates mastitis induced by S. aureus are still principally unknown. The purpose of this study is to investigate whether Se can inhibit mastitis induced by S. aureus through regulation of MerTK. Sixty BALB/c female mice were fed low, normal, or high Se concentrations for 7 weeks and then randomly divided into six groups (Se-Low Control group (LSN), Se-Normal Control group (NSN), Se-High Control group (HSN), Se-Low S. aureus group (LSS), Se-Normal S. aureus group (NSS), Se-High S. aureus group (HSS)). The regulation of Se on MerTK was detected via histopathological staining, western blot analysis, enzyme-linked immunosorbent assay, and qRT-PCR. With increased selenium concentrations, the levels of IL-1β, IL-6, and TNF-α decreased, while the phosphorylation levels of MerTK, PI3K, AKT, and mTOR increased. Therefore, this study showed that Se could alleviate S. aureus mastitis by activating MerTK and PI3K/AKT/mTOR pathway.

Objectives This study investigated the impact and related mechanisms of single-nucleotide variants (SNVs) in the HBV pre-S/S region on tumor development, and evaluated the role of antiviral therapy. Methods A retrospective analysis was conducted in 104 patients of the gray zone. HCC-associated SNVs were analyzed in baseline samples. Results HCC occurred in 15 patients (14.4%) during the median follow-up period of 10.4 years. Genotype B HBV-infected HCC patients had more T53C, A273G, and A529G SNVs and genotype C HBV-infected HCC patients had more T53C, G633A, and A3120G SNVs than HCC-free groups. Antiviral therapy reduced the risk of HCC in patients with HCC-associated SNVs in the gray zone both genotype B or C. Ectopic expression of replication-competent HBV plasmids in Huh7 cells expressing HCC-associated SNVs resulted in greater impairment of mitochondrial dynamics, increased production of reactive oxygen species (ROS), decreased mitochondrial membrane potential, lower ATP production, higher basal calcium levels, and reduced calcium buffering capacity compared to controls or wild-type HBV-expressing cells. Conclusions CHB patients in the gray zone remain at risk for HCC owing to both wild-type and HCC-associated HBV SNVs, especially the latter, inducing mitochondrial and metabolic dysfunctions. Antiviral therapy reduces the risk of HCC development in these patients.

The gel-spun ultra-high molecular weight polyethylene (UHMWPE) fibers were prepared at the industrial production line with different gel solution concentrations of 15 wt%, 18 wt% and 24 wt%. The difference in ultimate structure and mechanical properties of UHMWPE fibers for different gel solution concentrations were analyzed by tensile testing, differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and small angle X-ray scattering (SAXS). With the increase of gel solution concentration, the ultimate mechanical properties of UHMWPE fibers were decreased and the crystallization and orientation of UHMWPE fibers became inferior. Besides, both the average shish length () and shish misorientation (Bϕ) of UHMWPE fibers were decreased with the increase of gel solution concentration. In addition, the appropriate increase of spinning temperature led to the further optimization of the ultimate structure and mechanical properties of UHMWPE fibers.

Ultra-high molecular weight polyethylene (UHMWPE)/chitin nanocrystal (CNC) fibers were prepared. Compared with the pure UHMWPE fibers, the ultimate tensile strength and Young’s modulus of UHMWPE/CNC fibers are improved by 15.7% and 49.6%, respectively, with the addition of chitin nanocrystals (CNCs) of 1 wt%. The melting temperature (Tm) of UHMWPE/CNC fibers was higher than that of pure UHMWPE fibers. Pure UHMWPE fibers and UHMWPE/CNC fibers were characterized with respect to crystallinity, orientation and kebab structure by wide-angle X-ray diffraction (WAXD), small-angle X-ray scattering (SAXS) and scanning electron microscopy (SEM). It is found that the CNCs act as the shish structure in UHMWPE/CNC fibers and the kebab crystals are grown around the CNCs. There was almost no difference between pure UHMWPE fibers and UHMWPE/CNC fibers in orientation. But the degree of crystallinity of various stages of UHMWPE/CNC fibers was respectively higher than the corresponding stage of pure UHMWPE fibers. Moreover, the addition of 1 wt% CNCs improved the thickness of kebab crystals and accelerated the transformation of kebab to shish.

During the underground excavation, various flaws are frequently observed, which significantly decrease the mechanical properties of surrounding rock, as has been proven. As known, grouting technology is a means of reinforcement that efficiently enhances the stability of underground engineering. However, existing studies have mainly focused on increasing the strength of the slurry stone, and relatively less attention has been paid to the poor bonding effect at the interface between the slurry and the rock mass. In this work, we proposed to adopt slurry containing nano-silica sol to reinforce the fractured rock mass. Based on the mechanical model of micro–nano-siliceous slurry reinforcement for single fractured rock masses established in this paper, the effect and the mechanism of micro–nano-siliceous slurry reinforcement for fractured rock were explored through theoretical analysis, laboratory tests, and numerical simulations. Results showed that the application of micro–nano-siliceous slurry increased the friction and the bonding force at the slurry–rock interface, which led to a (σn·Δμ + Δc) reduction of the effective stress. The optimum incorporation rate of the nano-silica sol was determined to be 3% based on these indicators including slurry fluidity, slurry stone rate, and strength and deformation parameters of slurry stone. The peak strength of the sandstone specimens reinforced by the micro–nano-siliceous slurry increased by 16.49% those of the sandstones reinforced by the ordinary slurry, and the elastic energy accumulated by the former was higher. Scanning electron microscope images revealed that the incorporation of nano-silica sol distinctly improved the pore characteristics of the slurry-rock interface. Finally, on the basis of 1790 ventilation roadway of Shiyakou coal mine, the effectiveness and the feasibility of micro–nano-siliceous slurry for reinforcing underground engineering surrounding rocks were verified using numerical simulation.HighlightsThis paper developed a new micro–nano-siliceous grouting material.A mechanical model for fractured rock mass reinforced by new slurry was proposed.The optimal incorporation rate of nano-silica sol was determined by various means.This study demonstrated the effectiveness of the new grouting material in reinforcing fractured rock mass by control lab experiments and numerical simulation.The mechanisms of micro–nano-siliceous slurry to improve slurry–rock interface were revealed.

The multiple endothermic peaks of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P(HB-co-HV)) in differential scanning calorimetry (DSC) results, as one representative phenomenon of polymer with unique cocrystallization behavior, were generally considered as the results of melting/recrystallization. In this study, wide angle X-ray diffraction (WAXD) and small angle X-ray scattering (SAXS) experiments were conducted to analyze the phenomena of multiple endothermic peaks in DSC results. The results of these analyses indicated that the multiple endotherms were mainly caused by different lamellae structures. For P(HB-co-HV) with lower HV content, it was comprised of two structures of HV total exclusion and HV partial inclusion in the crystal lamellae. For P(HB-co-HV) with higher HV content, it was also comprised of two structures of HV total inclusion and HV partial inclusion in the crystal lamellae. However, only structure with HV partial inclusion in the crystal lamellae remained existing after first melting peak for all samples.

As a member of the potassium calcium-activated channel subfamily, increasing evidence suggests that KCNN4 was associated with malignancies. However, the roles and regulatory mechanisms of KCNN4 in PDAC have been little explored. In this work, we demonstrated that the level of KCNN4 in PDAC was abnormally elevated, and the overexpression of KCNN4 was induced by transcription factor AP-1. KCNN4 was closely correlated with unfavorable clinicopathologic characteristics and poor survival. Functionally, we found that overexpression of KCNN4 promoted PDAC cell proliferation, migration and invasion. Conversely, the knockdown of KCNN4 attenuated the growth and motility of PDAC cells. In addition to these, knockdown of KCNN4 promoted PDAC cell apoptosis and led to cell cycle arrest in the S phase. In mechanistic investigations, RNA-sequence revealed that the MET-mediated AKT axis was essential for KCNN4, encouraging PDAC cell proliferation and migration. Collectively, these findings reveal a function of KCNN4 in PDAC and suggest it’s an attractive therapeutic target and tumor marker. Our studies underscore a better understanding of the biological mechanism of KCNN4 in PDAC and suggest novel strategies for cancer therapy.

Microbeam wide-angle X-ray diffraction (WAXD) experiments were carried out at different structural knot positions of SIOC and M4 fibers of ultra-high molecular weight polyethylene (UHMWPE). The optical microscope images revealed that SIOC fiber had bamboo-like structural knots, and M4 fiber had chaotic distribution of structural knots. WAXD patterns showed the monoclinic unit cell in the whole M4 fiber, but different lamellar orientations in the bamboo joint of SIOC fiber. In addition, small-angle X-ray scattering (SAXS) patterns confirmed that the SIOC fiber contained uniform distribution of shish structures, and differential scanning calorimetry (DSC) measurements showed that its less branched and short chains benefited the orthorhombic-hexagonal phase transformation.

Autism spectrum disorders (ASD) affect approximately 1.0% of children worldwide with still increasing global prevalence. The fact that genetic factors contribute to less than 50% of ASD suggests some critical yet enigmatic roles of non-genetic factors in ASD etiology. Here, we reported that montelukast (MTK), a cysteinyl leukotriene receptor antagonist and one of the most commonly prescribed anti-asthma drugs, potently disrupted neuronal retinoic acid (RA) signaling and altered synaptic plasticity of the primary neurons from rat pre-frontal cortex (PFC). Prenatal or early postnatal exposure to MTK induced autistic-like behaviors in wild-type rats, which could be significantly alleviated by supplementing all-trans retinoic acid (atRA). MTK altered neuronal RA signaling and forebrain patterning in brain organoids derived from human embryonic stem cells through antagonizing RA in RA signaling. Meanwhile, molecular docking followed by biochemical validation strongly indicated that MTK could physically interact with RA receptors (RARs), e.g. RA receptor α (RARA). Furthermore, multi-center survey with a large Chinese ASD cohort suggested that MTK administration during early childhood might indeed increase the risk of ASD in children. Altogether, our findings have not only established MTK use as a yet unrecognized risk factor for human ASD, but highlighted the key importance of safer use of medicines to prevent ASD.