Correlation of thyroid function and sensitivity to thyroid hormone with spinal bone mineral content, bone mineral density, and osteoporotic vertebral fracture: A cross-sectional study based on NHANES.

Previous studies have demonstrated that thyroid hormone plays an important role in normal bone development, bone metabolism, and establishment of peak bone mass. However, the correlation of thyroid status with bone mineral content (BMC), bone mineral density (BMD), and osteoporotic vertebral fracture (OVF) is rarely discussed. The current study probes into the potential association between thyroid status and spinal BMC, BMD, and OVF from a novel perspective of thyroid function (TF) and sensitivity to thyroid hormone based on the National Health and Nutrition Examination Survey database. A total of 1844 participants were included in this study. The association of thyroid status with outcome variables, like spinal BMC, BMD, and OVF, was analyzed using thyroid function indices and sensitivity to thyroid hormone indices as influence factors. The correlation of them were assessed using univariate and multivariable weighted linear regression, weighted logistic regression models, restricted cubic spline model, and subgroup analyses. The results of this study showed that the association of free triiodothyronine (FT3)/free thyroxine (FT4) with BMC remained negatively associated after adjustment for all covariates. Higher thyroid peroxidase antibody (TPOAb) was significantly associated with an increased risk of developing OVF in both unadjusted and adjusted models. In addition, the results of the restricted cubic spline model were consistent with the weighted multivariate regression analysis after adjustment. The results of this cross-sectional study showed that higher FT3/FT4 and TPOAb were associated with decreased spinal BMC and the increased risk of OVF, indicating a complex link between thyroid status and bone health. Therefore, patients with hyperthyroidism, hypothyroidism, autoimmune thyroid disease, or abnormal peripheral thyroid sensitivity, especially who with elevated TPOAb or FT3/FT4, should focus on the prevention of vertebral osteopenia, osteoporosis, and OVF.

Adipose stem cell exosomes promote mitochondrial autophagy through the PI3K/AKT/mTOR pathway to alleviate keloids.

BACKGROUND: Fibrosis with unrelieved chronic inflammation is an important pathological change in keloids. Mitochondrial autophagy plays a crucial role in reducing inflammation and inhibiting fibrosis. Adipose stem cell-derived exosomes, a product of adipose stem cell paracrine secretion, have pharmacological effects, such as anti-inflammatory and antiapoptotic effects, and mediate autophagy. Therefore, this study aims to investigate the function and mechanism of adipose stem cell exosomes in the treatment of keloids. METHOD: We isolated adipose stem cell exosomes under normoxic and hypoxic condition to detect their effects on keloid fibroblast proliferation, migration, and collagen synthesis. Meanwhile, 740YPDGFR (PI3K/AKT activator) was applied to detect the changes in autophagic flow levels and mitochondrial morphology and function in keloid fibroblasts. We constructed a human keloid mouse model by transplanting human keloid tissues into six-week-old (20-22 g; female) BALB/c nude mice, meanwhile, we applied adipose stem cell exosomes to treat the mouse model and observed the retention and effect of ADSC exosomes in vivo. RESULTS: ADSC exosomes can inhibit the PI3K/AKT/mTOR signaling pathway. The exosomes of ADSCs decreased the inflammatory level of KFs, enhanced the interaction between P62 and LC3, and restored the mitochondrial membrane potential. In the human keloid mouse model, ADSC exosomes can exist stably, promote mitochondrial autophagy in keloid tissue, improve mitochondrial morphology, reduce inflammatory reaction and fibrosis. Meanwhile, At the same time, the exosomes derived from hypoxic adipose stem cells have played a more effective role in both in vitro and in vivo experiments. CONCLUSIONS: Adipose stem cell exosomes inhibited the PI3K/AKT/mTOR pathway, activated mitochondrial autophagy, and alleviated keloid scars.

Design, Synthesis, and Anticancer Activity of Novel Enmein-Type Diterpenoid Derivatives Targeting the PI3K/Akt/mTOR Signaling Pathway.

The enmein-type diterpenoids are a class of anticancer ent-Kaurane diterpnoids that have received much attention in recent years. Herein, a novel 1,14-epoxy enmein-type diterpenoid 4, was reported in this project for the first time. A series of novel enmein-type diterpenoid derivatives were also synthesized and tested for anticancer activities. Among all the derivatives, compound 7h exhibited the most significant inhibitory effect against A549 cells (IC50 = 2.16 µM), being 11.03-folds better than its parental compound 4. Additionally, 7h exhibited relatively weak anti-proliferative activity (IC50 > 100 µM) against human normal L-02 cells, suggesting that it had excellent anti-proliferative selectivity for cancer cells. Mechanism studies suggested that 7h induced G0/G1 arrest and apoptosis in A549 cells by inhibiting the PI3K/AKT/mTOR pathway. This process was associated with elevated intracellular ROS levels and collapsed MMP. In summary, these data identified 7h as a promising lead compound that warrants further investigation of its anticancer properties.

OligoM-Cancer: A multidimensional information platform for deep phenotyping of heterogenous oligometastatic cancer.

Patients with oligometastatic cancer (OMC) exhibit better response to local therapeutic interventions and a more treatable tendency than those with polymetastatic cancers. However, studies on OMC are limited and lack effective integration for systematic comparison and personalized application, and the diagnosis and precise treatment of OMC remain controversial. The application of large language models in medicine remains challenging because of the requirement of high-quality medical data. Moreover, these models must be enhanced using precise domain-specific knowledge. Therefore, we developed the OligoM-Cancer platform (http://oligo.sysbio.org.cn), pioneering knowledge curation that depicts various aspects of oligometastases spectrum, including markers, diagnosis, prognosis, and therapy choices. A user-friendly website was developed using HTML, FLASK, MySQL, Bootstrap, Echarts, and JavaScript. This platform encompasses comprehensive knowledge and evidence of phenotypes and their associated factors. With 4059 items of literature retrieved, OligoM-Cancer includes 1345 valid publications and 393 OMC-associated factors. Additionally, the included clinical assistance tools enhance the interpretability and credibility of clinical translational practice. OligoM-Cancer facilitates knowledge-guided modeling for deep phenotyping of OMC and potentially assists large language models in supporting specialised oligometastasis applications, thereby enhancing their generalization and reliability.

Shaping the future of gastrointestinal cancers through metabolic interactions with host gut microbiota.

Gastrointestinal (GI) cancers represent a significant global health challenge, driving relentless efforts to identify innovative diagnostic and therapeutic approaches. Recent strides in microbiome research have unveiled a previously underestimated dimension of cancer progression that revolves around the intricate metabolic interplay between GI cancers and the host's gut microbiota. This review aims to provide a comprehensive overview of these emerging metabolic interactions and their potential to catalyze a paradigm shift in precision diagnosis and therapeutic breakthroughs in GI cancers. The article underscores the groundbreaking impact of microbiome research on oncology by delving into the symbiotic connection between host metabolism and the gut microbiota. It offers valuable insights into tailoring treatment strategies to individual patients, thus moving beyond the traditional one-size-fits-all approach. This review also sheds light on novel diagnostic methodologies that could transform the early detection of GI cancers, potentially leading to more favorable patient outcomes. In conclusion, exploring the metabolic interactions between host gut microbiota and GI cancers showcases a promising frontier in the ongoing battle against these formidable diseases. By comprehending and harnessing the microbiome's influence, the future of precision diagnosis and therapeutic innovation for GI cancers appears more optimistic, opening doors to tailored treatments and enhanced diagnostic precision.

Observation of Fast Low-Temperature Oxygen Ion Conduction in CeO2/ß"-Al2O3 Heterostructure.

Semiconductor ion fuel cells (SIFCs) have demonstrated impressive ionic conductivity and efficient power generation at temperatures below 600 °C. However, the lack of understanding of the ionic conduction mechanisms associated with composite electrolytes has impeded the advancement of SIFCs toward lower operating temperatures. In this study, a CeO2/ß″-Al2O3 heterostructure electrolyte is introduced, incorporating ß″-Al2O3 and leveraging the local electric field (LEF) as well as the manipulation of the melting point temperature of carbonate/hydroxide (C/H) by Na+ and Mg2+ from ß″-Al2O3. This design successfully maintains swift interfacial conduction of oxygen ions at 350 °C. Consequently, the fuel cell device achieved an exceptional ionic conductivity of 0.019 S/cm and a power output of 85.9 mW/cm2 at 350 °C. The system attained a peak power density of 1 W/cm2 with an ultra-high ionic conductivity of 0.197 S/cm at 550 °C. The results indicate that through engineering the LEF and incorporating the lower melting point C/H, there approach effectively observed oxygen ion transport at low temperatures (350 °C), effectively overcoming the issue of cell failure at temperatures below 419 °C. This study presents a promising methodology for further developing high-performance semiconductor ion fuel cells in the low temperature range of 300-600 °C.

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.