Mutual regulation of microglia and astrocytes after Gas6 inhibits spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202502000-00032/figure1/v/2024-05-28T214302Z/r/image-tiff Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury. Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction. However, the mechanisms involved remain unclear. In this study, we found that after spinal cord injury, resting microglia (M0) were polarized into pro-inflammatory phenotypes (MG1 and MG3), while resting astrocytes were polarized into reactive and scar-forming phenotypes. The expression of growth arrest-specific 6 (Gas6) and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury. In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia, and even inhibited the cross-regulation between them. We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway. This, in turn, inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways. In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord, thereby promoting tissue repair and motor function recovery. Overall, Gas6 may play a role in the treatment of spinal cord injury. It can inhibit the inflammatory pathway of microglia and polarization of astrocytes, attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment, and thereby alleviate local inflammation and reduce scar formation in the spinal cord.

Flexible Hydrazone-Linked Metal-Covalent Organic Frameworks with Copper Clusters for Efficient Electrocatalytic Oxygen Evolution Reaction.

Despite the challenges associated with the synthesis of flexible metal-covalent organic frameworks (MCOFs), these offer the unique advantage of maximizing the atomic utilization efficiency. However, the construction of flexible MCOFs with flexible building units or linkages has rarely been reported. In this study, novel flexible MCOFs are constructed using flexible building blocks and copper clusters with hydrazone linkages. The heterometallic frameworks (Cu, Co) are prepared through the hydrazone linkage coordination method and evaluated as catalysts for the oxygen evolution reaction (OER). Owing to the spatial separation and functional cooperation of the heterometallic MCOF catalysts, the as-synthesized MCOFs exhibited outstanding catalytic activities with an overpotential of 268.8 mV at 10 mA cm-2 for the OER in 1 M KOH, which is superior to those of the reported covalent organic frameworks (COFs)-based OER catalysts. Theoretical calculations further elucidated the synergistic effect of heterometallic active sites within the linkages and frameworks, contributing to the enhanced OER activity. This study thus introduces a novel approach to the fundamental design of flexible MCOF catalysts for the OER, emphasizing their enhanced atomic utilization efficiency.

A Multi-Center, Multi-Parametric MRI Dataset of Primary and Secondary Brain Tumors.

Brain metastases (BMs) and high-grade gliomas (HGGs) are the most common and aggressive types of malignant brain tumors in adults, with often poor prognosis and short survival. As their clinical symptoms and image appearances on conventional magnetic resonance imaging (MRI) can be astonishingly similar, their accurate differentiation based solely on clinical and radiological information can be very challenging, particularly for "cancer of unknown primary", where no systemic malignancy is known or found. Non-invasive multiparametric MRI and radiomics offer the potential to identify these distinct biological properties, aiding in the characterization and differentiation of HGGs and BMs. However, there is a scarcity of publicly available multi-origin brain tumor imaging data for tumor characterization. In this paper, we introduce a multi-center, multi-origin brain tumor MRI (MOTUM) imaging dataset obtained from 67 patients: 29 with high-grade gliomas, 20 with lung metastases, 10 with breast metastases, 2 with gastric metastasis, 4 with ovarian metastasis, and 2 with melanoma metastasis. This dataset includes anonymized DICOM files alongside processed FLAIR, T1-weighted, contrast-enhanced T1-weighted, T2-weighted sequences images, segmentation masks of two tumor regions, and clinical data. Our data-sharing initiative is to support the benchmarking of automated tumor segmentation, multi-modal machine learning, and disease differentiation of multi-origin brain tumors in a multi-center setting.

A universal packaging substrate for mechanically stable assembly of stretchable electronics.

Stretchable electronics commonly assemble multiple material modules with varied bulk moduli and surface chemistry on one packaging substrate. Preventing the strain-induced delamination between the module and the substrate has been a critical challenge. Here we develop a packaging substrate that delivers mechanically stable module/substrate interfaces for a broad range of stiff and stretchable modules with varied surface chemistries. The key design of the substrate was to introduce module-specific stretchability and universal adhesiveness by regionally tuning the bulk molecular mobility and surface molecular polarity of a near-hermetic elastic polymer matrix. The packaging substrate can customize the deformation of different modules while avoiding delamination upon stretching up to 600%. Based on this substrate, we fabricated a fully stretchable bioelectronic device that can serve as a respiration sensor or an electric generator with an in vivo lifetime of 10 weeks. This substrate could be a versatile platform for device assembly.

PDCD2 as a prognostic biomarker in glioma correlates with malignant phenotype.

Programmed cell death 2 (PDCD2) is related to cancer progression and chemotherapy sensitivity. The role of PDCD2 in solid cancers (excluding hematopoietic malignancies) and their diagnosis and prognosis remains unclear. The TCGA, CGGA, GEPIA, cBioPortal, and GTEx databases were analyzed for expression, prognostic value, and genetic modifications of PDCD2 in cancer patients. Functional enrichment analysis, CCK8, colony formation assay, transwell assay, and xenograft tumor model were undertaken to study the PDCD2's biological function in glioma (GBMLGG). The PDCD2 gene was associated with solid cancer progression. In the functional enrichment analysis results, PDCD2 was shown to participate in several important GBMLGG biological processes. GBMLGG cells may be inhibited in their proliferation, migration, invasion, and xenograft tumor growth by knocking down PDCD2. Our research can provide new insights into solid cancer prognostic biomarkers of PDCD2.

Flexible wafer-scale bifunctional metasurface based on nanoimprinting.

Metasurfaces have demonstrated remarkable capabilities in manipulating light fields across diverse applications. However, current research tends to examine these functionalities in isolation, prompting a growing interest in integrating different functionalities within a singular metasurface device. In this paper, we propose and experimentally demonstrate a bifunctional metasurface capable of providing concealment and sensing functions simultaneously. Specifically, the proposed nanostructure effectively operates as a one-way mirror, exhibiting an average reflection rate of approximately 90% under external illumination, alongside an absorption rate of 87.9% from the opposite direction of incidence. This functionality renders it suitable for privacy-enhancing building windows. Meanwhile, this nanostructure also integrates liquid sensing capabilities boasting a sensitivity of 464 nm/RIU, which is particularly valuable for monitoring liquid-based corrosion. The experimental performance of the prepared 6-inch nanohole-patterned metasurface closely aligns with the simulations, and the utilization of flexible polyethylene terephthalate (PET) film, coupled with nanoimprint lithography technology, enables a direct and cost-effective manufacturing process that can be scaled up for widespread applications.

Insight into the Contact Mechanism of Ag/Al-Si Interface for the Front-Side Metallization of TOPCon Silicon Solar Cells.

For N-type tunnel-oxide-passivated-contact silicon solar cells, optimal Ag/Al-Si contact interface is crucial to improve the efficiency. However, the specific roles of Ag and Al at the interface have not been clearly elucidated. Hence, this work delves into the sintering process of Ag/Al paste and examines the impact of the Ag/Al-Si interface structure on contact quality. By incorporating TeO2 into PbO-based Ag/Al paste, the Ag/Al-Si interface structure can be modulated. It can be found that TeO2 accelerates the sintering of Ag powder and increases Ag colloids within glass layer, while it simultaneously impedes the diffusion of molten Al. It leads to a reduced Al content near the Ag/Al-Si interface and a shorter diffusion distance of Al into Si. Notably, it can be demonstrated that the diffusion of Al in Si layer is more effective to reduce the contact resistance than the precipitation of Ag colloids. Therefore, the PbO-based Ag/Al paste, which favors Al diffusion, leads to solar cells with lower contact resistance and series resistance, higher fill factor, and superior photoelectric conversion efficiency. In brief, this work is significant for optimizing metallization of silicon solar cells and other semiconductor devices.

High estrogen induces trans-differentiation of vascular smooth muscle cells to a macrophage-like phenotype resulting in aortic inflammation via inhibiting VHL/HIF1a/KLF4 axis.

Estrogen is thought to have a role in slowing down aging and protecting cardiovascular and cognitive function. However, high doses of estrogen are still positively associated with autoimmune diseases and tumors with systemic inflammation. First, we administered exogenous estrogen to female mice for three consecutive months and found that the aorta of mice on estrogen develops inflammatory manifestations similar to Takayasu arteritis (TAK). Then, in vitro estrogen intervention was performed on mouse aortic vascular smooth muscle cells (MOVAS cells). Stimulated by high concentrations of estradiol, MOVAS cells showed decreased expression of contractile phenotypic markers and increased expression of macrophage-like phenotypic markers. This shift was blocked by tamoxifen and Krüppel-like factor 4 (KLF4) inhibitors and enhanced by Von Hippel-Lindau (VHL)/hypoxia-inducible factor-1α (HIF-1α) interaction inhibitors. It suggests that estrogen-targeted regulation of the VHL/HIF-1α/KLF4 axis induces phenotypic transformation of vascular smooth muscle cells (VSMC). In addition, estrogen-regulated phenotypic conversion of VSMC to macrophages is a key mechanism of estrogen-induced vascular inflammation, which justifies the risk of clinical use of estrogen replacement therapy.

Contribution of mechanoreceptors to spinal cord injury-induced mechanical allodynia.

ABSTRACT: Evidence from previous studies supports the concept that spinal cord injury (SCI)-induced neuropathic pain (NP) has its neural roots in the peripheral nervous system. There is uncertainty about how and to which degree mechanoreceptors contribute. Sensorimotor activation-based interventions (eg, treadmill training) have been shown to reduce NP after experimental SCI, suggesting transmission of pain-alleviating signals through mechanoreceptors. The aim of the present study was to understand the contribution of mechanoreceptors with respect to mechanical allodynia in a moderate mouse contusion SCI model. After genetic ablation of tropomyosin receptor kinase B expressing mechanoreceptors before SCI, mechanical allodynia was reduced. The identical genetic ablation after SCI did not yield any change in pain behavior. Peptidergic nociceptor sprouting into lamina III/IV below injury level as a consequence of SCI was not altered by either mechanoreceptor ablation. However, skin-nerve preparations of contusion SCI mice 7 days after injury yielded hyperexcitability in nociceptors, not in mechanoreceptors, which makes a substantial direct contribution of mechanoreceptors to NP maintenance unlikely. Complementing animal data, quantitative sensory testing in human SCI subjects indicated reduced mechanical pain thresholds, whereas the mechanical detection threshold was not altered. Taken together, early mechanoreceptor ablation modulates pain behavior, most likely through indirect mechanisms. Hyperexcitable nociceptors seem to be the main drivers of SCI-induced NP. Future studies need to focus on injury-derived factors triggering early-onset nociceptor hyperexcitability, which could serve as targets for more effective therapeutic interventions.

Research Progress on Active Ingredients and Product Development of Lycium ruthenicum Murray.

Lycium ruthenicum Murray possesses significant applications in both food and medicine, including antioxidative, anti-tumor, anti-fatigue, anti-inflammatory, and various other effects. Consequently, there has been a surge in research endeavors dedicated to exploring its potential benefits, necessitating the organization and synthesis of these findings. This article systematically reviews the extraction and content determination methods of active substances such as polysaccharides, anthocyanins, flavonoids, and polyphenols in LRM in the past five years, as well as some active ingredient composition determination methods, biological activities, and product development. This review is divided into three main parts: extraction and determination methods, their bioactivity, and product development. Building upon prior research, we also delve into the economic and medicinal value of Lycium ruthenicum Murray, thereby contributing significantly to its further exploration and development. It is anticipated that this comprehensive review will serve as a valuable resource for advancing research on Lycium ruthenicum Murray.

Knockdown of vitellogenin receptor based on minute insect RNA interference methods affects the initial mature egg load in the pest natural enemy Trichogramma dendrolimi.

Vitellogenin receptor (VgR) plays a crucial role in oogenesis by mediating endocytosis of vitellogenin and a portion of the yolk proteins in many insect species. However, the function of VgR in minute parasitoid wasps is largely unknown. Here, we applied Trichogramma dendrolimi, a minute egg parasitoid, as a study model to investigate the function of VgR in parasitoids. We developed RNA interference (RNAi) methods based on microinjection of prepupae in T. dendrolimi. RNAi employs nanomaterial branched amphipathic peptide capsules (BAPC) as a carrier for double-stranded RNA (dsRNA), significantly enhancing delivery efficiency. Also, artificial hosts without medium were used to culture the injected prepupae in vitro. Utilizing these methods, we found that ovarian growth was disrupted after knockdown of TdVgR, as manifested by the suppressed development of the ovariole and the inhibition of nurse cell internalization by oocytes. Also, the initial mature egg load in the ovary was significantly reduced. Notably, the parasitic capacity of the female adult with ovarian dysplasia was significantly decreased, possibly resulting from the low availability of mature eggs. Moreover, ovarian dysplasia in T. dendrolimi caused by VgR deficiency are conserved despite feeding on different hosts. The results confirmed a critical role of TdVgR in the reproductive ability of T. dendrolimi and provided a reference for gene functional studies in minute insects.

Sustained delivery of NT-3 and curcumin augments microenvironment modulation effects of decellularized spinal cord matrix hydrogel for spinal cord injury repair.

Decellularized extracellular matrix hydrogel, especially that derived from spinal cord (DSCM hydrogel), has been actively considered as a functional biomaterial for remodeling the extracellular matrix of the native tissue, due to its unique characteristics in constructing pro-regenerative microenvironment for neural stem cells (NSCs). Furthermore, DSCM hydrogel can provide multiple binding domains to growth factors and drugs. Therefore, both exogenous neurotrophic factors and anti-inflammatory drugs are highly desired to be incorporated into DSCM hydrogel, which may synergistically modulate the complex microenvironment at the lesion site after spinal cord injury (SCI). Herein, neurotrophin-3 (NT-3) and curcumin (Cur) were integrated into DSCM hydrogel for SCI therapy. Due to different affinities to the DSCM hydrogel, NT-3 underwent a controlled release manner, while curcumin released explosively within the first 24 h, followed by rather sustained but slower release. The integration of both NT-3 and curcumin significantly enhanced NSCs proliferation and their neuronal differentiation. Meanwhile, the release of curcumin promoted macrophages polarization into anti-inflammatory subtypes, which further facilitated NSCs differentiation into neurons. The in situ injected DSCM + NT3 + Cur hydrogel exerted superior capability in alleviating the inflammatory responses in rat contused spinal cord. Compared to DSCM hydrogel alone, DSCM + NT3 + Cur hydrogel more significantly promoted the recruitment of NSCs and their neuronal differentiation at the lesion site. These outcomes favored functional recovery, as evidenced by the improved hind limb movement. Overall, the bioactive DSCM hydrogel can serve as a multifunctional carrier for cooperatively release of growth factors and drugs, which significantly benefits microenvironment regulation and nerve regeneration after SCI.

UV aging may enhance adsorption capacity of Poly (butylene adipate-co-terephthalate) (PBAT) to heavy metals and toxicity to zebrafish.

Compared with the fossil-based plastics, biodegradable plastics are more easily decomposed into small-sized particles (e.g., microplastics). However, the role of aged biodegradable plastics in being vector of co-existed pollutants and potential toxicological effects remain to be elucidated. The present study selected micro-sized biodegradable polymer Poly (butylene adipate-co-terephthalate) (PBAT) as the object, aiming to explore its aging process, environmental behavior with heavy metals (Cu and Pb), and the toxic effects on zebrafish. The results showed that distinct changes such as cracks and severe deformation can be observed on the surface of PBAT after 60 days of UV aging, and the functional groups changed consequently. The maximum adsorption capacity of aged PBAT for Cu and Pb reached 0.967 and 0.939 mg·g-1, which increased by 1.32 and 1.46 times, respectively. The results of 7-day acute toxicology experiments suggested that the adsorption behavior of aged PBAT may alleviate the toxic effects of heavy metals Cu and Pb on zebrafish in short-term exposure, however it could simultaneously cause a serious imbalance of intestinal microorganisms in zebrafish. As demonstrated, the coexistence of aged PBAT and heavy metals (Cu, Pb) can seriously reduce the intestinal microbial diversity and richness of zebrafish, which may induce more serious toxicity and disease in long-term exposure to pollutants. This study could provide fundamental data for better understanding on the adsorption behavior and ecological risk of aged biodegradable plastics with coexisted pollutants.

Magnetic Seeding of SPIO-BMSCs Into a Biphasic Scaffold Can Promote Tendon-Bone Healing After Rotator Cuff Repair.

BACKGROUND: The tendon-bone interface (TBI) in the rotator cuff has a poor intrinsic capacity for healing, which increases the risk of retear after rotator cuff repair (RCR). However, facilitating regeneration of the TBI still remains a great clinical challenge. Herein, the authors established a novel strategy based on magnetic seeding to enhance the TBI regeneration. HYPOTHESIS: Magnetic seeding bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide (SPIO-BMSCs) into a biphasic scaffold can promote tendon-bone healing after RCR. STUDY DESIGN: Controlled laboratory study. METHODS: BMSCs were labeled with SPIOs. Prussian blue staining, CCK-8 tests, Western blot, and quantitative reverse transcription polymerase chain reaction (PCR) were used to determine the optimal effect concentration of SPIOs on cell bioactivities and abilities. Then SPIO-BMSCs were magnetically seeded into a biphasic scaffold under a magnetic field. The seeding efficacy was assessed by a scanning electron microscope, and the potential mechanism in chondrogenic differentiation after seeding SPIO-BMSCs into the scaffold was evaluated by Western blot and PCR. Furthermore, the effect of SPIO-BMSC/biphasic scaffold on tendon-bone healing after RCR using a rat model was examined using histological analysis, enzyme-linked immunosorbent assay, and biomechanical evaluation. RESULTS: BMSCs labeled with 100 µg/mL SPIO had no effect on cell bioactivities and the ability of chondrogenic differentiation. SPIO-BMSCs were magnetically seeded into a biphasic scaffold, which offered a high seeding efficacy to enhance chondrogenic differentiation of SPIO-BMSCs via the CDR1as/miR-7/FGF2 pathway for TBI formation in vitro. Furthermore, in vivo application of the biphasic scaffold with magnetically seeded SPIO-BMSCs showed their regenerative potential, indicating that they could significantly accelerate and promote TBI healing with superior biomechanical properties after RCR in a rat rotator cuff tear model. CONCLUSION: Magnetically seeding SPIO-BMSCs into a biphasic scaffold enhanced seeding efficacy to promote cell distribution and condensation. This construct enhanced the chondrogenesis process via the CDR1as/miR-7/FGF2 pathway and further promoted tendon-bone healing after RCR in a rat rotator cuff tear model. CLINICAL RELEVANCE: This study provides an alternative strategy for improving TBI healing after RCR.

Causal associations of cognition, intelligence, education, health and lifestyle factors with cervical spondylosis: a mendelian randomization study.

Background: Education, cognition, and intelligence are phenotypically and genetically related. Education has been shown to have a protective effect on the risk of developing cervical spondylosis. However, it is unclear whether cognition and intelligence have independent causal effects on cervical spondylosis, and whether health and lifestyle factors influence this association. Methods: We first assessed the independent effects of education, cognition, and intelligence on cervical spondylosis by two-sample Mendelian randomization and multivariable Mendelian randomization analysis, and evaluated 26 potential association mediators using two-step Mendelian randomization, and calculated the median proportion. Results: The results showed that only education had an independent causal effect on cervical spondylosis, and had a protective effect on the risk of cervical spondylosis (ß: 0.3395; se: 0.166; p < 0.05; OR:0.71; [95%CI: 0.481-0.943]. Of the 26 potential associated mediators, a factor was identified: SHBG (mediated proportion: 2.5%). Univariable Mendelian randomization results showed that the risk factors for cervical spondylosis were time spent watching TV (OR:1.96; [95%CI: 1.39-2.76]), smoking (OR:2.56; [95%CI: 1.061-1.486]), body mass index (OR:1.26; [95%CI: 1.124-1.418]), percentage of body fat (OR:1.32; [95%CI: 1.097-1.593]), major depression (OR:1.27; [95%CI: 1.017-1.587]) and sitting height (OR:1.15; [95%CI: 1.025-1.291]). Protective factors include computer using (OR:0.65; [95%CI: 0.418-0.995]), sex hormone binding globulin (OR:0.87; [95%CI: 0.7955-0.951]) and high-density lipoprotein (OR:0.90; [95%CI: 0.826-0.990]). Conclusion: Our findings demonstrate the causal and independent effects of education on cervical spondylosis and suggest that lifestyle media may be a priority target for the prevention of cervical spondylosis due to low educational attainment.

Weak-Interaction Environment in a Composite Electrolyte Enabling Ultralong-Cycling High-Voltage Solid-State Lithium Batteries.

Poly(vinylidene fluoride) (PVDF)-based solid electrolytes with a Li salt-polymer-little residual solvent configuration are promising candidates for solid-state batteries. Herein, we clarify the microstructure of PVDF-based composite electrolyte at the atomic level and demonstrate that the Li+-interaction environment determines both interfacial stability and ion-transport capability. The polymer works as a "solid diluent" and the filler realizes a uniform solvent distribution. We propose a universal strategy of constructing a weak-interaction environment by replacing the conventional N,N-dimethylformamide (DMF) solvent with the designed 2,2,2-trifluoroacetamide (TFA). The lower Li+ binding energy of TFA forms abundant aggregates to generate inorganic-rich interphases for interfacial compatibility. The weaker interactions of TFA with PVDF and filler achieve high ionic conductivity (7.0 × 10-4 S cm-1) of the electrolyte. The solid-state Li||LiNi0.8Co0.1Mn0.1O2 cells stably cycle 4900 and 3000 times with cutoff voltages of 4.3 and 4.5 V, respectively, as well as deliver superior stability at -20 to 45 °C and a high energy density of 300 Wh kg-1 in pouch cells.

Three-Dimensional Structure Light Robot-Assisted Frameless Stereotactic Brain Biopsy.

BACKGROUND AND OBJECTIVES: To assess the feasibility, accuracy, and safety of 3-dimensional (3D) structure light robot-assisted frameless stereotactic brain biopsy. METHODS: Five consecutive patients (3 males, 2 females) were included in this study. The patients' clinical, imaging, and histological data were analyzed, and all patients received a 3D structure light robot-assisted frameless stereotactic brain biopsy. The raw and/or analyzed data of the study are available from the corresponding author. RESULTS: The statistical results showed a mean age of 59.6 years (range 40-70 years), a mean target depth of 60.9 mm (range 53.5-65.8 mm), a mean radial error of 1.2 ± 0.7 mm (mean ± SD), a mean depth error of 0.7 ± 0.3 mm, and a mean absolute tip error of 1.5 ± 0.6 mm. The calculated Pearson product-moment correlation coefficient (r = 0.23) revealed no correlation between target depth and absolute tip error. All biopsy needles were placed in line with the planned trajectory successfully, and diagnostic specimens were harvested in all cases. Histopathological analysis revealed lymphoma (2 cases), lung adenocarcinoma (1 case), glioblastoma multiforme (1 case), and oligodendroglioma (1 case). CONCLUSION: Surface registration using the 3D structure light technique is fast and precise because of the achievable million-scale point cloud data of the head and face. 3D structure light robot-assisted frameless stereotactic brain biopsy is feasible, accurate, and safe.

Fully Biodegradable Packaging Films for Fresh Food Storage Based on Oil-Infused Bacterial Cellulose.

Fully biodegradable packaging materials are demanded to resolve the issue of plastic pollution. However, the fresh food storage performance of biodegradable materials is generally much lower than that of plastics due to their high permeability, microbial friendliness, and limited stretchability and transparency. Here a biodegradable packaging material is reported with high fresh food storage performance based on an oil-infused bacterial cellulose (OBC) porous film. The oil infusion significantly improved cellulose's food-keeping performance by reducing its gas permeability, increasing its stretchability and transparency, and enabling the active release of green vapor-phase preservative molecules, while maintaining its intrinsically high degradability. Strawberries stored in a container with the OBC lid at 23 °C after 5 days exhibited a moldy rate of 0%, in contrast to the 100% moldy rate of those stored by poly(ethylene). Enhanced storage performance is also obtained on tomatoes, pork, and shrimp. The OBC film is naturally degraded after being buried in wet soil at 30 °C for 9 days, identical to the degradation rate of bacterial cellulose. The liquid seal strategy broadly applies to different celluloses, providing a general option for developing cellulose-based biodegradable packaging materials.

Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

BACKGROUND: Atherosclerosis (AS) is a persistent inflammatory condition triggered and exacerbated by several factors including lipid accumulation, endothelial dysfunction and macrophages infiltration. Nobiletin (NOB) has been reported to alleviate atherosclerosis; however, the underlying mechanism remains incompletely understood. METHODS: This study involved comprehensive bioinformatic analysis, including multidatabase target prediction; GO and KEGG enrichment analyses for function and pathway exploration; DeepSite and AutoDock for drug binding site prediction; and CIBERSORT for immune cell involvement. In addition, target intervention was verified via cell scratch assays, oil red O staining, ELISA, flow cytometry, qRT‒PCR and Western blotting. In addition, by establishing a mouse model of AS, it was demonstrated that NOB attenuated lipid accumulation and the extent of atherosclerotic lesions. RESULTS: (1) Altogether, 141 potentially targetable genes were identified through which NOB could intervene in atherosclerosis. (2) Lipid and atherosclerosis, fluid shear stress and atherosclerosis may be the dominant pathways and potential mechanisms. (3) ALB, AKT1, CASP3 and 7 other genes were identified as the top 10 target genes. (4) Six genes, including PPARG, MMP9, SRC and 3 other genes, were related to the M0 fraction. (5) CD36 and PPARG were upregulated in atherosclerosis samples compared to the normal control. (6) By inhibiting lipid uptake in RAW264.7 cells, NOB prevents the formation of foam cell. (7) In RAW264.7 cells, the inhibitory effect of oxidized low-density lipoprotein on foam cells formation and lipid accumulation was closely associated with the PPARG signaling pathway. (8) In vivo validation showed that NOB significantly attenuated intra-arterial lipid accumulation and macrophage infiltration and reduced CD36 expression. CONCLUSIONS: Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

TGF-ß1-triggered BMI1 and SMAD2 cooperatively regulate miR-191 to modulate bone formation.

Transforming growth factor ß 1 (TGF-ß1), as the most abundant signaling molecule in bone matrix, is essential for bone homeostasis. However, the signaling transduction of TGF-ß1 in the bone-forming microenvironment remains unknown. Here, we showed that microRNA-191 (miR-191) was downregulated during osteogenesis and further decreased by osteo-favoring TGF-ß1 in bone marrow mesenchymal stem cells (BMSCs). MiR-191 was lower in bone tissues from children than in those from middle-aged individuals and it was negatively correlated with collagen type I alpha 1 chain (COL1A1). MiR-191 depletion significantly increased osteogenesis and bone formation in vivo. Hydrogels embedded with miR-191-low BMSCs displayed a powerful bone repair effect. Mechanistically, transcription factors BMI1 and SMAD2 coordinately controlled miR-191 level. In detail, BMI1 and pSMAD2 were both upregulated by TGF-ß1 under osteogenic condition. SMAD2 activated miR-191 transcription, while BMI1 competed with SMAD2 for binding to miR-191 promoter region, thus disturbing the activation of SMAD2 on miR-191 and reducing miR-191 level. Altogether, our findings reveal that miR-191 regulated by TGF-ß1-induced BMI1 and SMAD2 negatively modulated bone formation and regeneration, and inhibition of miR-191 might be therapeutically useful to enhance bone repair in clinic.