Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by chronic visceral pain with a complex etiology and challenging treatment. Although accumulating evidence supports the involvement of central nervous system sensitization in the development of visceral pain, the precise molecular mechanisms remain incompletely understood. In this study, we highlight the critical regulatory role of lysine-specific demethylase 6B (KDM6B) in the anterior cingulate cortex (ACC) in chronic visceral pain. To simulate clinical IBS conditions, we utilized the neonatal maternal deprivation (NMD) mouse model. Our results demonstrated that NMD induced chronic visceral pain and anxiety-like behaviors in mice. Notably, the protein expression level of KDM6B significantly increased in the ACC of NMD mice, leading to a reduction in the expression level of H32K7me3. Immunofluorescence staining revealed that KDM6B primarily co-localizes with neurons in the ACC, with minimal presence in microglia and astrocytes. Injecting GSK-J4 (a KDM6B-specific inhibitor) into ACC of NMD mice, resulted in a significant alleviation in chronic visceral pain and anxiety-like behaviors, as well as a remarkable reduction in NR2B expression level. ChIP assay further indicated that KDM6B regulates NR2B expression by influencing the demethylation of H3K27me3. In summary, our findings underscore the critical role of KDM6B in regulating chronic visceral pain and anxiety-like behaviors in NMD mice. These insights provide a basis for further understanding the molecular pathways involved in IBS and may pave the way for targeted therapeutic interventions.

A Mesoporous Theranostic Platform for Ultrasound and Photoacoustic Dual Imaging-guided Photothermal and Enhanced Starvation Therapy for Cancer.

Tumor starvation therapy utilizing glucose oxidase (GOx), has gained traction due to its non-invasive and bio-safe attributes. However, its effectiveness is often hampered by severe hypoxia in the tumor microenvironment (TME), limiting GOx's catalytic activity. To address this issue, a multifunctional nanosystem based on mesoporous polydopamine nanoparticles (MPDA NPs) was developled to alleviate TME hypoxia. This nanosystem integrated GOx modification and loading of oxygenated perfluoropentane (PFP) and oxygen (O2) to address hypoxia-related challenges in the TME. Under NIR laser irradiation, the MPDA NPs exhibit significant photothermal conversion efficacy, activating targeted tumor photothermal therapy (PTT), while also serving as proficient photoacoustic (PA) imaging agents. The ensuing temperature rise facilitates O2 release and induces liquid-gas conversion of PFP, generating microbubbles for enhanced ultrasound (US) imaging signals. The supplied oxygen alleviates local hypoxia, thereby enhancing GOx-mediated endogenous glucose consumption for tumor starvation. Overall, the integration of ultrasound/photoacoustic dual imaging-guided PTT and starvation therapy within MPDA-GOx@PFP@O2 nanoparticles (MGPO NPs) presents a promising platform for enhancing the efficacay of tumor treatment by overcoming the complexities of the TME. STATEMENT OF SIGNIFICANCE: A multifunctional MPDA-based theranostic nanoagent was developed for US/PAI imaging-guided PTT and starvation therapy against tumor hypoxia by direct O2 delivery. The incorporation of oxygenated perfluoropentane (PFP) within the mesoporous structure of MGPO not only enables efficient US imaging but also helps in alleviating tumor hypoxia. Moreover, the strong near-infrared (NIR) absorption of MGPO NPs promote the generation of PFP microbubbles and release of oxygen, thereby enhancing US imaging and GOx-mediated starvation therapy. Such a multifunctional nanosystem leverages synergistic effects to enhance therapeutic efficacy while incorporating US/PA imaging for precise visualization of the tumor.

Characteristics of Pickering emulsions stabilized by microgel particles of five different plant proteins and their application.

Pickering emulsions stabilized by protein particles are of great interest for use in real food systems. This study was to investigate the properties of microgel particles prepared from different plant proteins, i.e., soybean protein isolate (SPI), pea protein isolate (PPI), mung bean protein isolate (MPI), chia seed protein isolate (CSPI), and chickpea protein isolate (CPI). MPI protein particles had most desirable Pickering emulsion forming ability. The particles of SPI and PPI had similar particle size (316.23 nm and 294.80 nm) and surface hydrophobicity (2238.40 and 2001.13) and emulsion forming ability, while the CSPI and CPI particle stabilized emulsions had the least desirable properties. The MPI and PPI particle stabilized Pickering emulsions produced better quality ice cream than the one produced by SPI particle-stabilized emulsions. These findings provide insight into the properties of Pickering emulsions stabilized by different plant protein particles and help expand their application in emulsions and ice cream.

Comparison of valganciclovir versus foscarnet for the treatment of cytomegalovirus viremia in adult acute leukemia patients after allogeneic hematopoietic cell transplantation.

Cytomegalovirus (CMV) reactivation increases treatment-related mortality (TRM) after allogeneic hematopoietic cell transplantation (allo-HCT). We analyzed 141 adult acute leukemia (AL) patients suffered allo-HCT between 2017 and 2021, who developed CMV viremia post-HCT and treated with valganciclovir or foscarnet, to evaluate effectiveness and safety of both drugs. Viremia clearance rates (14 and 21 d post treatment) and toxicities were similar in two groups. However, valganciclovir was associated with a lower cumulative incidence of CMV recurrence within 180 days (16.7% vs. 35.7%, p=0.029) post CMV clearance. Finally, 2-year TRM was lower in valganciclovir group (9.7% ± 0.2% vs. 26.2% ± 0.3%, p = 0.026), result a superior 2-year overall survival (OS; 88.1% ± 5.2% vs. 64.4% ± 5.5%, p = 0.005) and leukemia-free survival (LFS; 82.0% ± 5.9% vs. 58.9% ± 5.6%, p = 0.009). Valganciclovir might decrease CMV viremia recurrence and led to better long-term outcome than foscarnet in adult AL patients developed CMV viremia post-HCT. Considering the inherent biases of retrospective study, well-designed trials are warranted to validate our conclusion.

Histological chorioamnionitis and pathological stages on very preterm infant outcomes.

AIMS: Histological chorioamnionitis (HCA) is a condition linked to preterm birth and neonatal infection and its relationship with various pathological stages in extremely preterm neonates, and with their associated short- and long-term consequences, remains a subject of research. This study investigated the connection between different pathological stages of HCA and both short-term complications and long-term outcomes in preterm infants born at or before 32 weeks of gestational age. METHODS: Preterm infants born at ≤ 32 weeks of gestation who underwent placental pathology evaluation and were followed-up at 18-24 months of corrected age were included. Neonates were classified based on their exposure to HCA and were further subdivided into different groups according to maternal inflammatory responses (MIR) and fetal inflammatory responses (FIR) stages. We compared short-term complications during their hospital stay between the HCA-exposed and -unexposed groups and examined the influence of HCA stages on long-term outcomes. RESULTS: The HCA group exhibited distinct characteristics such as higher rates of premature rupture of membranes > 18 h, reduced amniotic fluid, early-onset sepsis, bronchopulmonary dysplasia and intraventricular haemorrhage (IVH) grades III-IV (P < 0.05). The moderate-severe HCA group displayed lower gestational age, lower birth weight and higher incidence of IVH (grades III-IV) and preterm sepsis compared with the mild HCA group (P < 0.05). After adjusting for confounders, the MIR stages 2-3 group showed associations with cognitive impairment and cerebral palsy (P < 0.05), and the FIR stages 2-3 group also showed poor long-term outcomes and cognitive impairment (P < 0.05). CONCLUSIONS: Moderate-severe HCA was associated with increased early-onset sepsis, severe IVH and poor long-term outcomes, including cognitive impairment and cerebral palsy. Vigilant prevention strategies are warranted for severe HCA cases in order to mitigate poorer clinical outcomes.

Freeze-thaw stability of Pickering emulsion stabilized by modified soy protein particles and its application in plant-based ice cream.

Pickering emulsions are of great interest to the food industry and their freeze-thaw stability important when used in frozen foods. Particles of soybean isolate (SPI) were heat treated and then crosslinked with transglutaminase (TG) enzyme to produce Pickering emulsions. The protein particles produced using unheated and uncrosslinked SPI (NSPI) was used as the benchmark. The mean particle size, absolute zeta potential, and surface hydrophobicity of protein particles produced using heat treatment and TG crosslinking (at 40 U/g) SPI (HSPI-TG-40) were the highest and substantially higher than those produced using NSPI. The thermal treatment of protein particles followed by crosslinking with TG enzyme improved the freeze-thaw stability of Pickering emulsions stabilized by them. The Pickering emulsions produced using HSPI-TG-40 had the lowest temperature for ice crystal formation and they had better freeze-thaw stability. The plant-based ice cream prepared by HSPI-TG-40 particle-stabilized Pickering emulsions had suitable texture and freeze-thaw stability compared to the ice cream produced using NSPI. The Pickering particles produced using heat treatment of SPI followed by crosslinking with TG (at 40 U/g) produced the most freeze-thaw stable Pickering emulsions. These Pickering particles and Pickering emulsions could be used in frozen foods such as ice cream.

Metabolome profiling and transcriptome analysis filling the early crucial missing steps of piperine biosynthesis in Piper nigrum L.

Black pepper (Piper nigrum L.), the world renown as the King of Spices, is not only a flavorsome spice but also a traditional herb. Piperine, a species-specific piper amide, is responsible for the major bioactivity and pungent flavor of black pepper. However, several key steps for the biosynthesis of piperoyl-CoA (acyl-donor) and piperidine (acyl-acceptor), two direct precursors for piperine, remain unknown. In this study, we used guilt-by-association analysis of the combined metabolome and transcriptome, to identify two feruloyldiketide-CoA synthases responsible for the production of the C5 side chain scaffold feruloyldiketide-CoA intermediate, which is considered the first and important step to branch metabolic fluxes from phenylpropanoid pathway to piperine biosynthesis. In addition, we also identified the first two key enzymes for piperidine biosynthesis derived from lysine in P. nigrum, namely a lysine decarboxylase and a copper amine oxidase. These enzymes catalyze the production of cadaverine and 1-piperideine, the precursors of piperidine. In vivo and in vitro experiments verified the catalytic capability of them. In conclusion, our findings revealed enigmatic key steps of piperine biosynthetic pathway and thus provide a powerful reference for dissecting the biosynthetic logic of other piper amides.

Advances of blend films based on natural food soft matter: Multi-scale structural analysis.

The blend films made of food soft matter are of growing interest to the food packaging industries as a pro-environment packaging option. The blend films have become a novel pattern to replace traditional plastics gradually due to their characteristics of biodegradability, sustainability, and environmental friendliness. This review discussed the whole process of the manufacturing of food soft matter blend films from the raw material to the application due to multi-scale structural analysis. There are 3 stages and 12 critical analysis points of the entire process. The raw material, molecular self-assembly, film-forming mechanism and performance test of blend films are investigated. In addition, 11 kinds of blend films with different functional properties by casting are also preliminarily described. The industrialization progress of blend films can be extended or facilitated by analysis of the 12 critical analysis points and classification of the food soft matter blend films which has a great potential in protecting environment by developing sustainable packaging solutions.

Identification of Na+/K+-ATPase Inhibitor Bufalin as a Novel Pseudorabies Virus Infection Inhibitor In Vitro and In Vivo.

Pseudorabies virus (PRV), an alpha herpesvirus, induces significant economic losses to the swine industry and infects multiple kinds of animals. Therefore, it is of great importance to explore anti-PRV compounds. In this study, to explore the anti-PRV compounds, a library of natural compounds was screened through a cell-based ELISA assay, and it was discovered that bufalin, a Na+/K+-ATPase inhibitor, had a robust inhibitory effect on PRV replication. A time-of-addition experiment and temperature-shift assay showed that bufalin significantly inhibited the entry stage of PRV. NaCl- or KCl-treatment showed that NaCl could enhance the inhibitory effect of bufalin on PRV replication, whereas there was no significant effect under the treatment of KCl. Meanwhile, it was also found that bufalin possessed antiviral activity against other alpha herpesviruses, including human herpes simplex virus type 1 (HSV-1) and chicken Marek's disease virus (MDV). Finally, it was found that bufalin could decrease the viral load in multiple tissues, and reduce the morbidity and mortality in PRV-challenged BALB/c mice. Overall, our findings demonstrated that bufalin has the potential to be developed as an anti-PRV compound.

Effect of Physical Modifications on Physicochemical and Functional Properties of Walnut Protein.

Walnut protein is a high-quality vegetable protein with promising applications in the food industry; however, its potential is hindered by low solubility and associated properties. We utilized various physical modification techniques (cold plasma; ball milling; superfine grinding; ultrasound; wet ball milling; and high-pressure microjet) to enhance walnut proteins' physicochemical and functional properties. The changes in particle size, microstructure, surface hydrophobicity, fluorescence, solubility, foaming, and emulsification were investigated. Cold plasma and ultrasound treatments minimally affected particle size and morphology. Cold plasma increased the particle size D4,3 from 145.20 µm to 152.50 µm. Ultrasonication reduced the particle size D4,3 to 138.00 µm. The variation was within ±10 µm, while the particle size of walnut protein significantly decreased after the other four modification treatments. The greatest variation in particle size was in the superfine grinding, with the D4,3 being reduced to 23.80 µm. Ultrasound treatment converted the ß-sheet into an α-helix, while the other methods transformed the α-helix into a ß-sheet. The dispersion stability notably improved after wet ball milling and high-pressure microjet treatments, which was accompanied by a significant increase in solubility from 6.9% (control) to 13.6% (wet ball milling) and 31.7% (high-pressure microjet). The foaming and emulsification properties were also enhanced through these modifications (foaming improved from 47% to 55.33% and emulsification improved from 4.32 m2/g to 8.27 m2/g). High-pressure microjet treatment proved most effective at improving solubility in the functional properties of walnut protein. These findings are expected to help broaden the potential utilization of walnut protein in the food industry, including in beverages and emulsions.

Hydrothermal Extraction and Characterization of Natural Hydroxyapatite from Waste Bovine Femur Bone.

The management of large amounts of bio-wastes, such as bovine femurs from kitchens and slaughterhouses, has long been a challenging issue. However, through the utilization of a hydrothermal process, it is possible to transform these bio-wastes into valuable products. In this study, we focused on extracting hydroxyapatite (HAp), the primary inorganic component of bovine femurs, for potential use in bone tissue engineering scaffolds. By subjecting the femurs to hydrothermal treatment at varying times and solvents, we successfully decomposed and removed the organic matter present, resulting in the extraction of HAp. To comprehensively evaluate the properties of the extracted HAp, we employed several characterization techniques that provided valuable insights into the structure, morphology, and elemental composition of the extracted HAp. Furthermore, we conducted a Cell Counting Kit-8 assay, which confirmed the favorable biocompatibility of the extracted HAp. Overall, this study highlights the potential of hydrothermal treatment as an environmentally friendly and cost-effective method for handling bio-waste, specifically bovine femurs. The extracted HAp exhibits promising characteristics, making it suitable for a wide range of biomedical applications. This research contributes to the sustainable utilization of bio-waste and underscores the importance of resourceful exploitation for environmental protection.

CircRREB1 mediates lipid metabolism related senescent phenotypes in chondrocytes through FASN post-translational modifications.

Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid metabolism, and upregulation of senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 is highly expressed in secondary generation chondrocytes and its deficiency can alleviate FASN related senescent phenotypes and osteoarthritis progression. CircRREB1 impedes proteasome-mediated degradation of FASN by inhibiting acetylation-mediated ubiquitination. Meanwhile, CircRREB1 induces RanBP2-mediated SUMOylation of FASN and enhances its protein stability. CircRREB1-FASN axis inhibits FGF18 and FGFR3 mediated PI3K-AKT signal transduction, then increased p21 expression. Intra-articular injection of adenovirus-CircRreb1 reverses the protective effects in CircRreb1 deficiency mice. Further therapeutic interventions could have beneficial effects in identifying CircRREB1 as a potential prognostic and therapeutic target for age-related OA.

Removal of chloramphenicol and resistance gene changes in electric-integrated vertical flow constructed wetlands.

The performance of an electric-integrated vertical flow constructed wetland (E-VFCW) for chloramphenicol (CAP) removal, changes in microbial community structure, and the fate of antibiotic resistance genes (ARGs) were evaluated. CAP removal in the E-VFCW system was 92.73% ± 0.78% (planted) and 90.80% ± 0.61% (unplanted), both were higher than the control system which was 68.17% ± 1.27%. The contribution of anaerobic cathodic chambers in CAP removal was higher than the aerobic anodic chambers. Plant physiochemical indicators in the reactor revealed electrical stimulation increased oxidase activity. Electrical stimulation enhanced the enrichment of ARGs in the electrode layer of the E-VFCW system (except floR). Plant ARGs and intI1 levels were higher in the E-VFCW than in the control system, suggesting electrical stimulation induces plants to absorb ARGs, reducing ARGs in the wetland. The distribution of intI1 and sul1 genes in plants suggests that horizontal transfer may be the main mechanism dispersing ARGs in plants. High throughput sequencing analysis revealed electrical stimulation selectively enriched CAP degrading functional bacteria (Geobacter and Trichlorobacter). Quantitative correlation analysis between bacterial communities and ARGs confirmed the abundance of ARGs relates to the distribution of potential hosts and mobile genetic elements (intI1). E-VFCW is effective in treating antibiotic wastewater, however ARGs potentially accumulate.

Bioactive mineralized small intestinal submucosa acellular matrix/PMMA bone cement for vertebral bone regeneration.

Polymethylmethacrylate (PMMA) bone cement extensively utilized for the treatment of osteoporotic vertebral compression fractures due to its exceptional handleability and mechanical properties. Nevertheless, the clinical application of PMMA bone cement is restricted by its poor bioactivity and excessively high modulus of elasticity. Herein, mineralized small intestinal submucosa (mSIS) was incorporated into PMMA to prepare a partially degradable bone cement (mSIS-PMMA) that provided suitable compressive strength and reduced elastic modulus compared to pure PMMA. The ability of mSIS-PMMA bone cement to promote the attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells was shown through cellular experiments carried out in vitro, and an animal osteoporosis model validated its potential to improve osseointegration. Considering these benefits, mSIS-PMMA bone cement shows promising potential as an injectable biomaterial for orthopedic procedures that require bone augmentation.

Gallocatechin Gallate Inhibits the Replication of Pseudorabies Virus via Suppressing the Entry and Release Stages in Its Replication Cycle.

The pseudorabies virus is a widespread swine pathogen that has caused significant economic losses to the global pig industry. Due to the emergence of PRV variant strains in recent years, vaccines cannot provide complete protection against the infection of PRV. Therefore, the research on antiviral compounds is of great importance for PRV treatment. In this study, an EGFP-labeled PRV was used to screen anti-PRV compounds from 86 natural product extracts. Gallocatechin gallate was found to efficiently inhibit the replication of PRV with a half-maximal inhibitory concentration (IC50) of 0.41 µM. In addition, it was found that gallocatechin gallate was unable to directly inactivate PRV and had no effect on the attachment stage of PRV. However, it was found that gallocatechin gallate significantly suppressed the viral entry stage. Furthermore, it was found that the release stage of PRV was also significantly suppressed by gallocatechin gallate. Together, this study found that gallocatechin gallate could efficiently inhibit the replication of PRV by suppressing the entry and release stages of PRV, which will contribute to the development of a new therapeutic strategy against PRV infection.

A novel circular RNA circRBMS3 regulates proliferation and metastasis of osteosarcoma by targeting miR-424-eIF4B/YRDC axis.

Circular RNAs (circRNAs) have been demonstrated to have critical regulatory roles in tumorigenesis. However, the contribution of circRNAs to OS (osteosarcoma) remains largely unknown. circRNA deep sequencing was performed to the expression of circRNAs between OS and chondroma tissues. The regulatory and functional role of circRBMS3 (a circRNA derived from exons 7 to 10 of the RBMS3 gene, hsa_circ_0064644) upregulation was examined in OS and was validated in vitro and in vivo, upstream regulator and downstream target of circRBMS3 were both explored. RNA pull down, a luciferase reporter assay, biotin-coupled microRNA capture and fluorescence in situ hybridization were used to evaluate the interaction between circRBMS3 and micro (mi)-R-424-5p. For in vivo tumorigenesis experiments, Subcutaneous and Orthotopic xenograft OS mouse models were built. Expression of circRBMS3 was higher in OS tissues due to the regulation of adenosine deaminase 1-acting on RNA (ADAR1), an abundant RNA editing enzyme. Our in vitro data indicated that ShcircRBMS3 inhibits the proliferation and migration of osteosarcoma cells. Mechanistically, we showed that circRBMS3 could regulate eIF4B and YRDC, through 'sponging' miR-424-5p. Furthermore, knockdown of circRBMS3 inhibited malignant phenotypes and bone destruction of OS in vivo. Our results reveal an important role for a novel circRBMS3 in the growth and metastasis of malignant tumor cells and offer a fresh perspective on circRNAs in OS progression.

CircFNDC3B regulates osteoarthritis and oxidative stress by targeting miR-525-5p/HO-1 axis.

Osteoarthritis (OA) is a common chronic degenerative joint disease associated with a variety of risk factors including aging, genetics, obesity, and mechanical disturbance. This study aimed to elucidate the function of a newly discovered circular RNA (circRNA), circFNDC3B, in OA progression and its relationship with the NF-κB signaling pathway and oxidative stress. The circFNDC3B/miR-525-5p/HO-1 axis and its relationship with the NF-κB signaling pathway and oxidative stress were investigated and validated using fluorescence in situ hybridization, real-time PCR, western blotting, immunofluorescence analysis, luciferase reporter assays, pull-down assays, and reactive oxygen species analyses. The functions of circFNDC3B in OA was investigated in vitro and in vivo. These evaluations demonstrated that circFNDC3B promotes chondrocyte proliferation and protects the extracellular matrix (ECM) from degradation. We also revealed that circFNDC3B defends against oxidative stress in OA by regulating the circFNDC3B/miR-525-5p/HO-1 axis and the NF-κB signaling pathway. Further, we found that overexpression of circFNDC3B alleviated OA in a rabbit model. In summary, we identified a new circFNDC3B/miR-525-5p/HO-1 signaling pathway that may act to relieve OA by alleviating oxidative stress and regulating the NF-κB pathway, resulting in the protection of the ECM in human chondrocytes, highlighting it as a potential therapeutic target for the treatment of OA.

CircZSWIM6 mediates dysregulation of ECM and energy homeostasis in ageing chondrocytes through RPS14 post-translational modification.

BACKGROUND: Circular RNAs (CircRNAs) are important and have different roles in disease progression. Herein, we aim to elucidate the roles of a novel CircRNA (CircZSWIM6) which is upregulated in ageing chondrocytes. METHODS: We verified the roles of CircZSWIM6 in senescent and osteoarthritis (OA) development in vitro through CircZSWIM6 knockdown and overexpression. RNA pulldown assay and RNA binding protein immunoprecipitation were performed to identify the interaction between CircZSWIM6 and Ribosomal protein S14 (RPS14). The roles of CircZSWIM6 in ageing-related OA were also confirmed in non-traumatic and traumatic model respectively. RESULTS: CircZSWIM6 regulates extracellular matrix (ECM) and energy metabolism in ageing chondrocyte. Mechanistically, CircZSWIM6 competitively bound to the E3 ligase STUB1 binding site on RPS14 (K125) to inhibit proteasomal degradation of RPS14 to maintain RPS14 function. CircZSWIM6-RPS14 axis is highly associated with AMPK signaling transduction, which keeps energy metabolism in chondrocyte. Furthermore, CircZSWIM6 AAV infection leads to senescent and OA phenotypes in a non-traumatic model and accelerates OA progression in a traumatic model. CONCLUSION: Our results revealed a significant role of CircZSWIM6 in age-related OA by regulating ECM metabolism and AMPK-associated energy metabolism. We highlight the CircZSWIM6-RPS14-PCK1-AMPK axis is a potential biomarker for OA.