Intra-Articular Injection of Interleukin-8 Neutralizing Monoclonal Antibody Effectively Attenuates Osteoarthritis Progression in Rabbits.

OBJECTIVE: Cytokines are implicated in the pathogenesis of osteoarthritis (OA), and this study aims to assess the therapeutic potential of an IL-8 neutralizing monoclonal antibody (mAb) for OA intervention. DESIGN: The study employed a rabbit model of OA induced by anterior cruciate ligament transection (ACLT) surgery to investigate the effects of an interleukin (IL)-8 neutralizing mAb, with hyaluronic acid (HA) used as a positive control. Primary outcomes assessed in the rabbits included cartilage repair, synovitis, joint effusion, changes in footprints, and lower limb loading conditions. RESULTS: Compared to HA, intra-articular injection of the IL-8 neutralizing mAb demonstrated a more pronounced attenuation of OA progression and enhancement of cartilage repair. We observed a reduction in synovitis and joint effusion, indications of bone marrow edema, as well as improvements in lower limb function. In knees treated with the neutralizing IL-8 mAb, there was a significant decrease in IL-8 levels within the synovial tissues. CONCLUSIONS: The IL-8 neutralizing mAb exhibits promising therapeutic potential in the management of OA by attenuating inflammation and facilitating cartilage repair. However, further investigations are warranted to comprehensively elucidate the underlying mechanisms, optimize treatment protocols, and ensure the long-term safety and efficacy of this innovative therapeutic approach.

Unlocking the Immunomodulatory Potential of Rosmarinic Acid Isolated from Punica granatum L. Using Bioactivity-Guided Approach: In Silico, In Vitro, and In Vivo Approaches.

BACKGROUND: Punica granatum L. is well-known for its multifaceted therapeutic potential, including anti-inflammatory and immunomodulatory activities. AIM: This study aimed to characterize an immunomodulatory compound isolated from Punica granatum L. using a bioactivity-guided approach. METHODS: Chromatographic techniques were adopted for isolation and purification of secondary metabolites. In silico, in vitro, and in vivo methods were performed to characterize the therapeutic potential of the isolated compound. RESULTS: Using preparative thin-layer chromatography, rosmarinic acid was isolated from F4 (column chromatography product obtained from a butanolic fraction of the extract). The impact of rosmarinic acid was assessed in rats using the neutrophil adhesion test, DTH response, and phagocytic index. In immunized rats, rosmarinic acid demonstrated significant immunomodulatory potential. Computational experiments, like molecular docking and molecular dynamics, were also conducted against two targeted receptors, Cereblon (PDB ID: 8AOQ) and human CD22 (PDB ID: 5VKM). Computational studies suggested that an increase in phagocytic index by rosmarinic acid could be attributed to inhibiting Cereblon and CD22. Pharmacokinetics and toxicity prediction also suggested the drug-likeness of rosmarinic acid. CONCLUSION: Rosmarinic acid is a potential candidate, but extensive research needs to be done to translate this molecule from bench to bedside.

Exosomes from adipose-derived stem cells activate sebocytes through the PI3K/AKT/SREBP-1 pathway to accelerate wound healing.

Sebocyte regeneration after injury is considered a key element of functional skin repair. Exosomes from adipose-derived stem cells (ADSCs-EXO) accelerate wound healing by promoting the proliferation of fibroblasts. However, the effects of ADSCs-EXO on sebocytes are largely unknown. In this study, the effects of ADSCs-EXO on sebocyte proliferation and migration were evaluated. The levels of phosphorylated AKT (p-AKT), AKT, sterol regulatory-element binding protein (SREBP), and perilipin-1 (PLIN-1) were detected with immunofluorescence, quantitative PCR, and western blot analysis. RNA-Seq was used to analyze the differential gene expression between the ADSCs-EXO group and the control group under anaerobic conditions. Lipogenesis was assessed with Nile red staining. In animal studies, full-thickness skin wounds in BALB/c mice were treated with gelatin methacrylate (GelMA) hydrogel-loaded sebocytes alone or in combination with ADSCs-EXO. Histopathological assessments of the wound tissues were performed Masson Trichrome staining, Immunohistochemical staining and so on. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway blocker LY294002 inhibited the effects of ADSCs-EXO on p-AKT and sebocytes proliferation. ADSCs-EXO also regulated the expression of SREBP-1 and PLIN-1 through the PI3K/AKT pathway in an oxygen level-dependent manner. In BALB/c mice, ADSCs-EXO accelerated sebocyte-assisted wound healing and regeneration. These in vitro and in vivo results supported that ADSCs-EXO can promote the regeneration of fully functional skin after injury through the PI3K/AKT-dependent activation of sebocytes.

Facile and Widely Applicable Route to Self-Adaptive Emissivity Modulation: Energy-Saving Demonstration with Transparent Wood.

The cooling power provided by radiative cooling is unwanted during cold hours. Therefore, self-adaptive regulation is desired for radiative cooling, especially in all-weather applications. However, current routes for radiative cooling regulation are constrained by substrates and complicated processing. Here, self-adaptive radiative cooling regulation on various potential substrates (transparent wood, PET, normal glass, and cement) was achieved by a Fabry-Perot structure consisting of a silver nanowires (AgNWs) bottom layer, PMMA spacer, and W-VO2 top layer. The emissivity-modulated transparent wood (EMTW) exhibits an emissivity contrast of 0.44 (ε8-13-L = ∼0.19 and ε8-13-H = ∼0.63), which thereby yields considerable energy savings across different climate zones. The emissivity contrast can be adjusted by varying the spinning parameters during the deposition process. Positive emissivity contrast was also achieved on three other industrially relevant substrates via this facile and widely applicable route. This proves the great significance of the approach to the promotion and wide adoption of radiative cooling regulation concept in the built environment.

From multi-omics approaches to personalized medicine in myocardial infarction.

Myocardial infarction (MI) is a prevalent cardiovascular disease characterized by myocardial necrosis resulting from coronary artery ischemia and hypoxia, which can lead to severe complications such as arrhythmia, cardiac rupture, heart failure, and sudden death. Despite being a research hotspot, the etiological mechanism of MI remains unclear. The emergence and widespread use of omics technologies, including genomics, transcriptomics, proteomics, metabolomics, and other omics, have provided new opportunities for exploring the molecular mechanism of MI and identifying a large number of disease biomarkers. However, a single-omics approach has limitations in understanding the complex biological pathways of diseases. The multi-omics approach can reveal the interaction network among molecules at various levels and overcome the limitations of the single-omics approaches. This review focuses on the omics studies of MI, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and other omics. The exploration extended into the domain of multi-omics integrative analysis, accompanied by a compilation of diverse online resources, databases, and tools conducive to these investigations. Additionally, we discussed the role and prospects of multi-omics approaches in personalized medicine, highlighting the potential for improving diagnosis, treatment, and prognosis of MI.

The interaction between alpha-synuclein and mitochondrial dysfunction in Parkinson's disease.

Parkinson's disease (PD) is an aging-associated neurodegenerative disorder with the hallmark of abnormal aggregates of alpha-synuclein (α-syn) in Lewy bodies (LBs) and Lewy neurites (LNs). Currently, pathogenic α-syn and mitochondrial dysfunction have been considered as prominent roles that give impetus to the PD onset. This review describes the α-syn pathology and mitochondrial alterations in PD, and focuses on how α-syn interacts with multiple aspects of mitochondrial homeostasis in the pathogenesis of PD.

Effect of Interlayer Bonding Temperature on the Bending Properties of Asphalt Concrete Core Wall.

In the construction process of an asphalt concrete impermeable core wall, the interlayer bonding of the core wall is the weak link of the core wall structure and also the focus of construction, so it is important to carry out research on the influence of interlayer bonding temperature on the bending performance of an asphalt concrete core wall. In this paper, we study whether asphalt concrete core walls could be treated with cold-bonding by fabricating small beam bending specimens with different interlayer bond temperatures and conducting bending tests on them at 2 °C. The effect of temperature variation on the bending performance of the bond surface under the asphalt concrete core wall is studied through experimental data analysis. The test results show that the maximum value of porosity of bituminous concrete specimens is 2.10% at lower bond surface temperature of -25 °C, which does not meet the specification requirement of less than 2%. The bending stress, strain, and deflection of bituminous concrete core wall increase with the increase of bond surface temperature, especially when the bond surface temperature is less than -10 °C. If the lower bonding surface temperature is less than 10 °C, the upper layer of asphalt mixture with large grain size aggregate cannot be effectively buried in the low bond surface, resulting in flat fracture and brittle damage to the specimen, which is detrimental to construction quality; therefore, the bonding surface should be heated so that the temperature of the bottom bonding surface is 30 °C. If the lower bonding surface temperature is 10 °C or above, no heating is required.

Myocardial infarction unveiled: Key miRNA players screened by a novel lncRNA-miRNA-mRNA network model.

BACKGROUND: Myocardial infarction (MI) is a major contributor to global mortality, and microRNAs (miRNAs) are important in its pathogenesis. Identifying blood miRNAs with clinical application potential for the early detection and treatment of MI is crucial. METHODS: We obtained MI-related miRNA and miRNA microarray datasets from MI Knowledge Base (MIKB) and Gene Expression Omnibus (GEO), respectively. A new feature called target regulatory score (TRS) was proposed to characterize the RNA interaction network. MI-related miRNAs were characterized using TRS, transcription factor (TF) gene proportion (TFP), and ageing-related gene (AG) proportion (AGP) via the lncRNA-miRNA-mRNA network. A bioinformatics model was then developed to predict MI-related miRNAs, which were verified by literature and pathway enrichment analysis. RESULTS: The TRS-characterized model outperformed previous methods in identifying MI-related miRNAs. MI-related miRNAs had high TRS, TFP, and AGP values, and combining the three features improved prediction accuracy to 0.743. With this method, 31 candidate MI-related miRNAs were screened from the specific-MI lncRNA-miRNA-mRNA network, associated with key MI pathways like circulatory system processes, inflammatory response, and oxygen level adaptation. Most candidate miRNAs were directly associated with MI according to literature evidence, except hsa-miR-520c-3p and hsa-miR-190b-5p. Furthermore, CAV1, PPARA and VEGFA were identified as MI key genes, and were targeted by most of the candidate miRNAs. CONCLUSIONS: This study proposed a novel bioinformatics model based on multivariate biomolecular network analysis to identify putative key miRNAs of MI, which deserve further experimental and clinical validation for translational applications.

Novel n-i CeO2/a-Al2O3 Heterostructure Electrolyte Derived from the Insulator a-Al2O3 for Fuel Cells.

Heterostructure technologies have been regarded as promising methods in the development of electrolytes with high ionic conductivity for low-temperature solid oxide fuel cells (LT-SOFCs). Here, a novel semiconductor/insulator (n-i) heterostructure strategy has been proposed to develop composite electrolytes for LT-SOFCs based on CeO2 and the insulator amorphous alumina (a-Al2O3). The constructed CeO2/a-Al2O3 electrolyte exhibits an ionic conductivity of up to 0.127 S cm-1, and its fuel cell achieves a maximum power density (MPD) of 1017 mW cm-2 with an open-circuit voltage (OCV) of 1.14 V at 550 °C without the short-circuiting problem, suggesting that the introduction of a-Al2O3 can effectively suppress the electron conduction of CeO2. It is found that the potential energy barrier at the heterointerfaces caused by the ultrawide band gap of the insulator a-Al2O3 plays an important role in restraining electron conduction. Simultaneously, the thermoelectric effect of the insulator induces more oxygen vacancies because of interface charge compensation, which further promotes ionic transport and results in high ionic conductivity and fuel cell performance. This study presents a practical n-i heterostructure electrolyte design, and further research confirmed the advanced functionality of the CeO2/a-Al2O3 electrolyte. Our study may open frontiers in the field of developing high-efficiency electrolytes of LT-SOFCs using insulating materials such as amorphous alumina.

Migration of solidification grain boundaries and prediction.

Solidification processing is essential to the manufacture of various metal products, including additive manufacturing. Solidification grain boundaries (SGBs) result from the solidification of the last liquid film between two abutting grains of different orientations. They can migrate, but unlike normal GB migration, SGB migration (SGBM) decouples SGBs from solidification microsegregation, further affecting material properties. Here, we first show the salient features of SGBM in magnesium-tin alloys solidified with cooling rates of 8-1690 °C/s. A theoretical model is then developed for SGBM in dilute binary alloys, focusing on the effect of solute type and content, and applied to 10 alloy systems with remarkable agreement. SGMB does not depend on cooling rate or time but relates to grain size. It tends to occur athermally. The findings of this study extend perspectives on solidification grain structure formation and control for improved performance (e.g. hot or liquation cracking during reheating, intergranular corrosion or fracture).

Upper Eyelid Blepharoplasty Improved the Overall Periorbital Aesthetics Ratio by Enhancing Harmony Between the Eyes and Eyebrows.

Purpose: In upper eyelid blepharoplasty, most aesthetic surgeons and patients focus on improvements in the appearance of the upper eyelids, such as changing the vertical dimension of the palpebral fissure and the width of the pretarsal crease. Nevertheless, appropriately balanced periorbital aesthetics stemming from harmony between the eyelids and eyebrows is often ignored. The aim of this study was to explore the use of upper eyelid blepharoplasty to improve the overall periorbital aesthetics by enhancing the harmony between the eyes and eyebrows in young Asian women. Patients and Methods: From December 2019 to December 2020, 45 young Asian female patients underwent external incision upper eyelidplasty without ptosis repair or brow lift at The Second Affiliated Hospital of Harbin Medical University. The pre- and 6-month post-operative follow-up changes in the overall periorbital aesthetics were studied retrospectively. Results: The vertical position of the eyebrows in the upper face and shape of the brow apex were significantly improved after surgery. As a result, the height of the upper face was increased. Furthermore, the facial width proportion and midface ratio were closer to the ideal aesthetic golden ratio due to changes in the size of the periorbital area. All patients were satisfied with the result, and they achieved excellent surgical outcomes for not only the upper eyelids but also the overall periorbital region. Conclusion: This study revealed that upper eyelid blepharoplasty, which enhances the appearance of the upper eyelids while regulating the eyelid position and shape of the eyebrows by considering the eye to eyebrow ratio, optimizes the proportion of the periorbital area and improves the overall periorbital aesthetics.

Translational Bioinformatics for Human Reproductive Biology Research: Examples, Opportunities and Challenges for a Future Reproductive Medicine.

Since 1978, with the first IVF (in vitro fertilization) baby birth in Manchester (England), more than eight million IVF babies have been born throughout the world, and many new techniques and discoveries have emerged in reproductive medicine. To summarize the modern technology and progress in reproductive medicine, all scientific papers related to reproductive medicine, especially papers related to reproductive translational medicine, were fully searched, manually curated and reviewed. Results indicated whether male reproductive medicine or female reproductive medicine all have made significant progress, and their markers have experienced the progress from karyotype analysis to single-cell omics. However, due to the lack of comprehensive databases, especially databases collecting risk exposures, disease markers and models, prevention drugs and effective treatment methods, the application of the latest precision medicine technologies and methods in reproductive medicine is limited.

New paraconic acids from the endophytic fungus Xylariaceae sp. J4.

Three new paraconic acids, xylariacinics A-C (1-3), were isolated from the endophyte Xylariaceae sp. J4 harbored in the medicinal plant Blumea balsamifera. Their structures were elucidated on the basis of extensive spectroscopic data including HRMS, and NMR. The antibacterial efficacies of compounds 1-3 were evaluated against a panel of bacteria such as Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa. Their antifungal activities were also tested against Colletotrichum gloeosporioides. Unfortunately, all of them were inactive.

MIKB: A manually curated and comprehensive knowledge base for myocardial infarction.

Myocardial infarction knowledge base (MIKB; http://www.sysbio.org.cn/mikb/; latest update: December 31, 2020) is an open-access and manually curated database dedicated to integrating knowledge about MI to improve the efficiency of translational MI research. MIKB is an updated and expanded version of our previous MI Risk Knowledge Base (MIRKB), which integrated MI-related risk factors and risk models for providing help in risk assessment or diagnostic prediction of MI. The updated MIRKB includes 9701 records with 2054 single factors, 209 combined factors, 243 risk models, 37 MI subtypes and 3406 interactions between single factors and MIs collected from 4817 research articles. The expanded functional module, i.e. MIGD, is a database including not only MI associated genetic variants, but also the other multi-omics factors and the annotations for their functional alterations. The goal of MIGD is to provide a multi-omics level understanding of the molecular pathogenesis of MI. MIGD includes 1782 omics factors, 28 MI subtypes and 2347 omics factor-MI interactions as well as 1253 genes and 6 chromosomal alterations collected from 2647 research articles. The functions of MI associated genes and their interaction with drugs were analyzed. MIKB will be continuously updated and optimized to provide precision and comprehensive knowledge for the study of heterogeneous and personalized MI.

Extracellular Vesicles from HIF-1α-Overexpressing Adipose-Derived Stem Cells Restore Diabetic Wounds Through Accelerated Fibroblast Proliferation and Migration.

PURPOSE: Inhibition of cellular adaptation to hypoxia can cause persistent inflammation, thereby increasing tissue damage and complicating wound healing in diabetes patients. Regulating cellular adaptation to hypoxic environments can help in effective wound repair. Hypoxia-inducible factor (HIF)-1α is a key regulator of cell hypoxia. Extracellular vesicles (EVs) regulate wound repair. This study investigated the mechanism of HIF-1α overexpression in adipose-derived stem cell extracellular vesicles (ADSCs-hEVs) in the repair of diabetic wounds. MATERIALS AND METHODS: HIF-1α expression in diabetes patients and healthy participants was studied. High-throughput sequencing, GO, and KEGG analysis revealed that ADSCs small extracellular vesicle hypoxia environments may increase HIF-1α expression by affecting cell metabolism, differentiation, and TGF-ß secretion, or by altering the PI3K/AKT pathway. Effect of addition of ADSCs-hEVs on cell proliferation and migration was investigated using Western blotting, EdU assay, transwell assay, and migration. In vivo, after 7, 14, and 21 days, important factors for diabetic wound healing were evaluated by immunohistochemistry, qRT-PCR, Masson staining, and H&E staining. RESULTS: HIF-1α expression decreased in the skin of diabetes patients; interleukin (IL)-6 expression increased, and growth factor-related indexes decreased. ADSCs-hEVs significantly increased the expression and secretion of growth factors, compared with ADSCs-EVs. In vivo, ADSC-hEV treatment accelerated the healing rate and improved the healing quality of diabetic wounds compared with ADSCs-EVs. CONCLUSION: Speed and quality of wound healing increased significantly in the ADSCs-hEVs group, which could inhibit early inflammation while promoting the secretion and expression of growth factors and extracellular matrix-related indexes.

Neuroprotective effect of paeoniflorin in the mouse model of Parkinson's disease through α-synuclein/protein kinase C δ subtype signaling pathway.

OBJECTIVES: Paeoniflorin, an active component of Radix Paeoniae Alba, has a neuroprotective effect in Parkinson's animal models. However, its mechanism of action remains to be determined. METHODS: In this study, we hypothesized that the neuroprotective effect of paeoniflorin occurs through the α-synuclein/protein kinase C δ subtype (PKC-δ) signaling pathway. We tested our hypothesis in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease. We evaluated the effects of paeoniflorin on the expression levels of signal components of the α-synuclein/PKC-δ pathway, cellular apoptosis and motor performance. RESULTS: Our results demonstrated that paeoniflorin restored the motor performance impairment caused by MPTP, inhibited apoptosis, and protected the ultrastructure of neurons. Paeoniflorin treatment also resulted in the dose-dependent upregulation of an antiapoptotic protein, B-cell lymphoma-2, at the mRNA and protein levels, similar to the effects of the positive control, selegiline. In contrast, paeoniflorin treatment downregulated the expression of pro-apoptotic proteins BCL2-Associated X2, α-synuclein, and PKC-δ at the mRNA and protein levels, as well as the level of the activated form of nuclear factor kappa B (p-NF-κB p65). CONCLUSIONS: Thus, our results showed that paeoniflorin exerts its neuroprotective effect by regulating the α-synuclein/PKC-δ signaling pathway to reduce neuronal apoptosis.

High Performance Low-Temperature Solid Oxide Fuel Cells Based on Nanostructured Ceria-Based Electrolyte.

Ceria based electrolyte materials have shown potential application in low temperature solid oxide fuel cells (LT-SOFCs). In this paper, Sm3+ and Nd3+ co-doped CeO2 (SNDC) and pure CeO2 are synthesized via glycine-nitrate process (GNP) and the electro-chemical properties of the nanocrystalline structure electrolyte are investigated using complementary techniques. The result shows that Sm3+ and Nd3+ have been successfully doped into CeO2 lattice, and has the same cubic fluorite structure before, and after, doping. Sm3+ and Nd3+ co-doped causes the lattice distortion of CeO2 and generates more oxygen vacancies, which results in high ionic conductivity. The fuel cells with the nanocrystalline structure SNDC and CeO2 electrolytes have exhibited excellent electrochemical performances. At 450, 500 and 550 °C, the fuel cell for SNDC can achieve an extraordinary peak power densities of 406.25, 634.38, and 1070.31 mW·cm-2, which is, on average, about 1.26 times higher than those (309.38, 562.50 and 804.69 mW·cm-2) for pure CeO2 electrolyte. The outstanding performance of SNDC cell is closely related to the high ionic conductivity of SNDC electrolyte. Moreover, the encouraging findings suggest that the SNDC can be as potential candidate in LT-SOFCs application.

Hypoxia adipose stem cell-derived exosomes promote high-quality healing of diabetic wound involves activation of PI3K/Akt pathways.

Refractory diabetic wounds can cause persistent inflammation and delayed healing due to hypoxia. Currently, no optimal solution is available. Exosomes of adipose stem cells (ADSCs-exo) may promote skin wound healing, however, molecular mechanisms remains mysterious. We found significantly enhanced survival and proliferation of adipose stem cells after hypoxia induction compared to normoxia. Here, we aimed to investigate if hypoxic adipose stem cells exosomes (HypADSCs-exo) participate in hypoxia adaptability and accelerate diabetic wound healing. Based on high-throughput sequencing, 215 microRNAs (miRNAs) were upregulated and 369 miRNAs downregulated in HypADSCs-exo compared to ADSCs-exo. Up-regulated miR-21-3p, miR-126-5p, miR-31-5p whereas down-regulated gene miR-99b and miR-146-a correlated with wound healing. According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), miRNAs might regulate cell metabolism, differentiation and Transforming growth factor-ß (TGF-ß) function. Consistently, HpyADSCs-exo could promote diabetic wounds healing and inhibit inflammation through PI3K/AKT signaling pathway. Collectively, HpyADSCs-exo can promote diabetic wound healing as an alternative strategy to improve wound healing.

Comparison of the application value of two commonly used minimally invasive spinal surgery in the treatment of lumbar disc herniation.

The aim of the study was to compare the application value of percutaneous transforaminal endoscopic discectomy (PTED) and microendoscopic discectomy (MED) in the treatment of lumbar disc herniation (LDH). From January 2017 to July 2018, 108 LDH patients undergoing surgical treatment in our hospital were collected and divided into PTED group (treated with PTED, n=50) and MED group (treated with MED, n=58). The operation parameter index level, complications, recurrence and pain score (VAS), Oswestry disability index (ODI) and Japanese Orthopaedic Association Scale (JOA) were compared between the two groups. VAS, ODI and JOA scores of the two groups were significantly decreased after operation (P<0.05), but there was no significant difference between the two groups (P>0.05). Complications and recurrence of the two groups were similar (P>0.05). MED was superior to PTED in the number of intraoperative fluoroscopy and operation time, while PTED was superior to MED in intraoperative blood loss, incision length, length of hospital stay and bed rest time (P<0.05). Both PTED and MED can effectively treat LDH. Referring to clinical data, PTED may be the first choice for LDH treatment.