Ultra-Fast-Healing Glassy Hyperbranched Plastics Capable of Restoring 26.4†MPa Tensile Strength within One Minute at Room Temperature.

The growing concern regarding widespread plastic pollution has propelled the development of sustainable self-healing plastics. Although considerable efforts have been dedicated to fabricating self-healing plastics, achieving rapid healing at room temperature is extremely challenging. Herein, we have developed an ultra-fast-healing glassy polyurethane (UGPU) by designing a hyperbranched molecular structure with a high density of multiple hydrogen bonds (H-bonds) on compliant acyclic heterochains and introducing trace water to form water bridge across the fractured surfaces. The compliant acyclic heterochains allow the dense multiple hydrogen bonds to form a frozen network, enabling tensile strength of up to 70 MPa and storage modulus of 2.5 GPa. The hyperbranched structure can drive the reorganization of the H-bonding network through the high mobility of the branched chains and terminals, thereby leading to self-healing ability at room temperature. Intriguingly, the presence of trace water vapor facilitates the formation of activated layers and the rearrangement of networks across the fractured UGPU sections, thereby enabling ultra-fast self-healing at room temperature. Consequently, the restored tensile strength after healing for 1 minute achieves a historic-record of 26.4 MPa. Furthermore, the high transparency (>90 %) and ultra-fast healing property of UGPU make it an excellent candidate for advanced optical and structural materials.

Room-temperature autonomous self-healing glassy polymers with hyperbranched structure.

Glassy polymers are extremely difficult to self-heal below their glass transition temperature (T g) due to the frozen molecules. Here, we fabricate a series of randomly hyperbranched polymers (RHP) with high density of multiple hydrogen bonds, which show T g up to 49 °C and storage modulus up to 2.7 GPa. We reveal that the hyperbranched structure not only allows the external branch units and terminals of the molecules to have a high degree of mobility in the glassy state, but also leads to the coexistence of "free" and associated complementary moieties of hydrogen bonds. The free complementary moieties can exchange with the associated hydrogen bonds, enabling network reconfiguration in the glassy polymer. As a result, the RHP shows amazing instantaneous self-healing with recovered tensile strength up to 5.5 MPa within 1 min, and the self-healing efficiency increases with contacting time at room temperature without the intervention of external stimuli.

Ten-gene signature reveals the significance of clinical prognosis and immuno-correlation of osteosarcoma and study on novel skeleton inhibitors regarding MMP9.

OBJECTIVES: This study aimed to identify novel targets in the carcinogenesis, therapy and prognosis of osteosarcoma from genomic level, together with screening ideal lead compounds with potential inhibition regarding MMP-9. METHODS: Gene expression profiles from GSE12865, GSE14359, GSE33382, GSE36001 and GSE99671 were obtained respectively from GEO database. Differentially expressed genes were identified, and functional enrichment analysis, such as GO, KEGG, GSEA, PPI were performed to make a comprehensive understanding of the hub genes. Next, a series of high-precision computational techniques were conducted to screen potential lead compounds targeting MMP9, including virtual screening, ADME, toxicity prediction, and accurate docking analysis. RESULTS: 10 genes, MMP9, CD74, SPP1, CXCL12, TYROBP, FCER1G, HCLS1, ARHGDIB, LAPTM5 and IGF1R were identified as hub genes in the initiation of osteosarcoma. Machine learning, multivariate Cox analysis, ssGSEA and survival analysis demonstrated that these genes had values in prognosis, immune-correlation and targeted treatment. Tow novel compounds, ZINC000072131515 and ZINC000004228235, were screened as potential inhibitor regarding MMP9, and they could bind to MMP9 with favorable interaction energy and high binding affinity. Meanwhile, they were precited to be efficient and safe drugs with low-ames mutagenicity, none weight evidence of carcinogenicity, as well as non-toxic with liver. CONCLUSIONS: This study revealed the significance of 10-gene signature in the development of osteosarcoma. Besides, drug candidates identified in this study provided a solid basis on MMP9 inhibitors' development.

Effects of Short-Term Limitation of Movement of the First Metatarsophalangeal Joint on the Biomechanics of the Ipsilateral Hip, Knee, and Ankle Joints During Walking.

BACKGROUND We analyzed the effect of limitation of movement of the first metatarsophalangeal joint (FMJ) on the biomechanics of the lower limbs during walking. MATERIAL AND METHODS Eight healthy college students completed walking under barefoot (BF) and FMJ constraint (FMJC) conditions. We synchronously collected kinematics and dynamics data, and calculated the torque, power, and work of hip, knee, and ankle joints. RESULTS Compared with normal conditions, when the FMJ is restricted from walking, the maximum ankle dorsiflexion angle is significantly increased (P<0.001), the maximum plantar flexion angle is significantly reduced (P<0.001), the maximum plantar flexion torque (P<0.001) and the maximum dorsiflexion torque (P<0.05) increased significantly, the maximum power increased significantly (P<0.001), the minimum power decreased significantly (P<0.001), and the negative work increased significantly (P<0.001). The torque of hip and knee joints increased significantly (P<0.05). CONCLUSIONS After the movement of the FMJ is restricted, the human body mainly compensates and transfers compensation by increasing the angle of dorsiflexion, increasing work and the activity level of surrounding muscles through the ankle joint, thereby increasing the torque load of the knee and hip joints to maintain the dynamic balance of kinematics. FMJC condition increases the energy consumption of the human ankle, knee, and hip joints during walking. The load is compensated by the gradual attenuation of the ankle, knee, and hip. Long-term limitation may cause damage to the posterior calf muscles and increase the incidence of knee arthritis.

Anatomic Study of Craniocervical Junction and Its Surrounding Structures in Endoscopic Transoral-Transpharyngeal Approach.

PURPOSE: This study aims to provide accurate and comprehensive data of craniocervical junction and its peripheral structures in order to provide a profound insight of craniocervical junction as well as to avoid complications during surgical procedures related to it. METHODS: Computed tomographic angiography (CTA) images of 120 individuals were reviewed, the measurements were performed on coronal, sagittal, and axial planes after 3-dimensional volume reconstruction. The authors measured pharyngeal tubercle, foramen magnum, and tuberculum anterius atlantis, which located based on the position of incisor. The anatomic features of other important bony landmarks, internal carotid artery, and vertebral artery were also fully studied so as to avoid being injured during the transoral-transpharyngeal procedure. RESULTS: During the endoscopic surgery to craniocervical junction, the bending angle of neuroendoscopy should be 14.27 ±â€Š4.51° and the entering depth should be about 72.57 ±â€Š8.72 mm. It is safe to work within the angle of 77.73 ±â€Š3.15° in axial plane and the safe penetration width from the axial midline is 20.05 ±â€Š3.11 mm in the level of foramina magnum. The distance from axial middle line to hypoglossal canal, external opening of carotid canal, and inner edge of jugular foramen was 9.78 ±â€Š0.72, 24.50 ±â€Š1.26, and 24.33 ±â€Š1.68 mm, respectively. CONCLUSIONS: These data in this study are valuable for neurosurgeons in clinical practice to reduce the possibility of complications and maximize the safety of surgeries; these data also contribute to the understanding of the anatomy of craniocervical junction and its surrounding structures.

Water Catchers within Sub-Nano Channels Promote Step-by-Step Zinc-Ion Dehydration Enable Highly Efficient Aqueous Zinc-Metal Batteries.

Zinc metal suffers from violent and long-lasting water-induced side reactions and uncontrollable dendritic Zn growth, which seriously reduce the coulombic efficiency (CE) and lifespan of aqueous zinc-metal batteries (AZMBs). To suppress the corresponding harmful effects of the highly active water, a stable zirconium-based metal-organic framework with water catchers decorated inside its sub-nano channels is used to protect Zn-metal. Water catchers within narrow channels can constantly trap water molecules from the solvated Zn-ions and facilitate step-by-step desolvation/dehydration, thereby promoting the formation of an aggregative electrolyte configuration, which consequently eliminates water-induced corrosion and side reactions. More importantly, the functionalized sub-nano channels also act as ion rectifiers and promote fast but even Zn-ions transport, thereby leading to a dendrite-free Zn metal. As a result, the protected Zn metal demonstrates an unprecedented cycling stability of more than 10 000 h and an ultra-high average CE of 99.92% during 4000 cycles. More inspiringly, a practical NH4V4O10//Zn pouch-cell is fabricated and delivers a capacity of 98 mAh (under high cathode mass loading of 25.7 mg cm-2) and preserves 86.2% capacity retention after 150 cycles. This new strategy in promoting highly reversible Zn metal anodes would spur the practical utilization of AZMBs.

A meta-analysis of randomized controlled trials comparing enteral immunonutrition (EIN) and standard enteral nutrition regarding biochemical, immunological, and clinical outcomes in gastrectomy patients with gastric cancer and investigating evidence networks for EIN formulae.

Introduction: For patients with gastric cancer who have undergone gastrectomy, recent research has shown that enteral immunonutrition (EIN) is more successful than enteral nutrition (EN) at boosting host immunity and, in turn, improving prognosis. The claimed outcomes, however, are inconsistent. Aim: This meta-analysis examines how EIN affects biochemical, immunological, and clinical outcomes for gastrectomy (GC) patients following gastrectomy and EIN formulae evidence networks. Material and methods: A comprehensive search of the Medline, EMBASE, Scopus, and Cochrane Library databases identified English-language peer-reviewed journal papers. The odds ratio (OR) and standard mean difference (SMD) were calculated, along with their 95% confidence intervals. The heterogeneity was assessed using Cochrane Q and I2 statistics and the appropriate p-value. The analysis used RevMan 5.3. Results: This meta-analysis included 10 RCTs involving 1409 GC patients, 714 of whom were assigned to EIN and 695 to EN. After EIN treatment, serum proalbumin, serum transferrin, lymphocyte count, and CD4+/CD8+ ratio had statistically significant standardised mean differences (SMDs) of 2.39, 2.39, 1.34, and 0.72, respectively. EIN reduces postoperative infectious complications with an OR of 0.63 (95% CI: 0.41-0.77) for infections, an OR of 0.63 for complications, and an SMD of -1.05 for systemic inflammations. A network diagram with high-quality data and a well-defined network design with consistent and accurate connection shows that EIN can improve serum protein levels, immunological parameters, and post-operative problems. Conclusions: The use of EIN has been shown to enhance cellular immunity, regulate inflammatory response, and decrease postoperative complications in GC patients who underwent major GI surgery.

Conjoint research of WGCNA, single-cell transcriptome and structural biology reveals the potential targets of IDD development and treatment and JAK3 involvement.

OBJECTIVES: This study conducted integrated analysis of bulk RNA sequencing, single-cell RNA sequencing and Weighted Gene Co-expression Network Analysis (WGCNA), to comprehensively decode the most essential genes of intervertebral disc degeneration (IDD); then mainly focused on the JAK3 macromolecule to identify natural compounds to provide more candidate drug options in alleviating IDD. METHODS: In the first part, we performed single-cell transcriptome analysis and WGCNA workflow to delineate the most pivotal genes of IDD. Then series of structural biology approaches and high-throughput virtual screening techniques were performed to discover potential compounds targeting JAK-STAT signaling pathway, such as Libdock, ADMET, precise molecular docking algorithm and in-vivo drug stability assessment. RESULTS: Totally 4 hub genes were determined in the development of IDD, namely VEGFA, MMP3, TNFSF11, and TIMP3, respectively. Then, 3 novel natural materials, ZINC000014952116, ZINC000003938642 and ZINC000072131515, were determined as potential compounds, with less toxicities and moderate ADME characteristics. In-vivo drug stability assessment suggested that these drugs could interact with JAK3, and their ligand-JAK3 complexes maintained the homeostasis in-vivo, which acted as regulatory role to JAK3 protein. Among them, ZINC000072131515, also known as Menaquinone, demonstrated significant protective roles to alleviate the progression of IDD in vitro, which proved the nutritional therapy in alleviating IDD. CONCLUSIONS: This study reported the essential genes in the development of IDD, and also the roles of Menaquinone to ameliorate IDD through inhibiting JAK3 protein. This study also provided more options and resources on JAK3 targeted screening, which may further expand the drug resources in the pharmaceutical market.

Deciphering the sequential changes of monocytes/macrophages in the progression of IDD with longitudinal approach using single-cell transcriptome.

Intervertebral disk degeneration (IDD) is a chronic inflammatory disease with intricate connections between immune infiltration and oxidative stress (OS). Complex cell niches exist in degenerative intervertebral disk (IVD) and interact with each other and regulate the disk homeostasis together. However, few studies have used longitudinal approach to describe the immune response of IDD progression. Here, we conducted conjoint analysis of bulk-RNA sequencing and single-cell sequencing, together with a series of techniques like weighted gene co-expression network analysis (WGCNA), immune infiltration analysis, and differential analysis, to systematically decipher the difference in OS-related functions of different cell populations within degenerative IVD tissues, and further depicted the longitudinal alterations of immune cells, especially monocytes/macrophages in the progression of IDD. The OS-related genes CYP1A1, MMP1, CCND1, and NQO1 are highly expressed and might be diagnostic biomarkers for the progression of IDD. Further landscape of IVD microenvironment showed distinct changes in cell proportions and characteristics at late degeneration compared to early degeneration of IDD. Monocytes/macrophages were classified into five distinct subpopulations with different roles. The trajectory lineage analysis revealed transcriptome alterations from effector monocytes/macrophages and regulatory macrophages to other subtypes during the evolution process and identified monocytes/macrophage subpopulations that had rapidly experienced the activation of inflammatory or anti-inflammatory responses. This study further proposed that personalized therapeutic strategies are needed to be formulated based on specific monocyte/macrophage subtypes and degenerative stages of IDD.

Integrated analysis of single-cell transcriptome and structural biology approach reveals the dynamics changes of NP subtypes and roles of Menaquinone in attenuating intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is a progressive and chronic disease, the mechanisms have been studied extensively as a whole, while the cellular heterogeneity of cells in nucleus pulposus (NP) tissues remained controversial for a long time. This study conducted integrated analysis through single-cell sequencing analysis, weighted gene co-expression network analysis (WGCNA), and differential expression analysis, to systematically decipher the longitudinal alterations of distinct NP subtypes, and also analyzed the most essential genes in the development of IDD. Then, this study further conducted structural biology method to discover the potential lead compounds through a suite of advanced approaches like high-throughput screening (HTVS), pharmaceutical characteristics assessment, CDOCKER module as well as molecular dynamics simulation, etc., aiming to ameliorate the progression of IDD. Totally 5 NP subpopulations were identified with distinct biological functions based on their unique gene expression patterns. The predominant dynamics changes mainly involved RegNPs and EffNPs, the RegNPs were mainly aggregated in normal NP tissues and drastically decreased in degenerative NP, while EffNPs, as pathogenic subtype, exhibited opposite phenomenon. Importantly, this study further reported the essential roles of Menaquinone in alleviating degenerative NP cells for the first time, which could provide solid evidence for the application of nutritional therapy in the treatment of IDD. This study combined scRNA-seq, bulk-RNA seq and HTVS techniques to systematically decipher the longitudinal changes of NP subtypes during IDD. EffNPs were considered to be 'chief culprit' in IDD progression, while the novel natural drug Menaquinone could reverse this phenomenon.Communicated by Ramaswamy H. Sarma.

Intratympanic steroid treatments rescued recurrent hearing loss following COVID-19 vaccination and detection of an intralabyrinthine schwannoma.

It remains unclear how to effectively treat rare cases of sudden and recurrent hearing losses which might coincidently follow vaccination. We report the first case, to our knowledge, of systemic and local steroid administration to successfully treat sudden and recurrent left-ear hearing loss, respectively, following a second dose of the BNT162b2 COVID-19 mRNA vaccination which inflammatory response potentially affected an existing left intralabyrinthine schwannoma in a young male patient. This case highlights the importance and timing of intratympanic steroid treatment strategies to suppress the progressive symptoms and restore hearing to a stable condition, and therefore avoid permanent hearing loss which would otherwise demand a surgical removal of the schwannoma to improve vertigo and reconstitute artificial hearing.

Bioinspired Design of High Vibration-Damping Supramolecular Elastomers Based on Multiple Energy-Dissipation Mechanisms.

Suppressing vibrations and noises is essential for our automated society. Here, inspired by the hierarchical dynamic bonds and phase separation of mussel byssal threads, we synthesize high-damping supramolecular elastomers (HDEs) via simple one-pot radical polymerization of butyl acrylate (BA), acrylic acid (AA), and vinylimidazole (VI). Interestingly, AA and VI not only form hydrogen bonds and ionic bonds simultaneously but also segregate into aggregates of different sizes, thereby successfully mimicking the hierarchical structure of mussel byssal threads. When applying external forces, the weak hydrogen bonds are broken at first and then the ionic bonds and aggregates are disrupted progressively from small to large deformations. Such multiple energy-dissipation mechanisms lead to the outstanding damping property of the HDEs. Therefore, the HDEs outperform commercially available rubbers in terms of sound absorption and vibration damping. Furthermore, the multiple energy-dissipation mechanisms impart the HDEs with high toughness (41.1 MJ/m3), tensile strength (21.3 MPa), and self-healing ability.

Revealing oxidative stress-related genes in osteoporosis and advanced structural biological study for novel natural material discovery regarding MAPKAPK2.

Objectives: This study aimed to find novel oxidative stress (OS)-related biomarkers of osteoporosis (OP), together with targeting the macromolecule Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) protein to further discover potential novel materials based on an advanced structural biology approach. Methods: Gene expression profiles of GSE35958 were obtained from the Gene Expression Omnibus (GEO) database, which were included for weighted gene co-expression network analysis (WGCNA) and differential analysis to identify the most correlated module, to identify OS-related hub genes in the progression of OP. Functional annotations were also analyzed on the interested module to get a comprehensive understanding of these genes. Then, a series of advanced structural biology methods, including high-throughput screening, pharmacological characteristic prediction, precise molecular docking, molecular dynamics simulation, etc., was implemented to discover novel natural inhibitor materials against the MAPKAPK2 protein. Results: The brown module containing 720 genes was identified as the interested module, and a group set of genes was determined as the hub OS-related genes, including PPP1R15A, CYB5R3, BCL2L1, ABCD1, MAPKAPK2, HSP90AB1, CSF1, RELA, P4HB, AKT1, HSP90B1, and CTNNB1. Functional analysis demonstrated that these genes were primarily enriched in response to chemical stress and several OS-related functions. Then, Novel Materials Discovery demonstrated that two compounds, ZINC000014951634 and ZINC000040976869, were found binding to MAPKAPK2 with a favorable interaction energy together with a high binding affinity, relatively low hepatoxicity and carcinogenicity, high aqueous solubility and intestinal absorption levels, etc., indicating that the two compounds were ideal potential inhibitor materials targeting MAPKAPK2. Conclusion: This study found a group set of OS-related biomarkers of OP, providing further insights for OS functions in the development of OP. This study then focused on one of the macromolecules, MAPKAPK2, to further discover potential novel materials, which was of great significance in guiding the screening of MAPKAPK2 potential materials.

Effect of Counterions on the Physicomechanical Properties of Copper-Nitrogen-Coordinated Metallosupramolecular Elastomers.

Metallosupramolecular elastomers have attracted much attention due to their excellent mechanical properties, flexible tailoring of performance, and responsiveness to photo and thermal stimuli. The physicomechanical properties of metallosupramolecular elastomers are highly dependent on metal salts and ligand units; however, the role of counterions lacks practical exploration. To this end, we synthesized a simple acrylate copolymer model and introduced copper salts with different counterions to construct dynamic copper-nitrogen coordination cross-linked networks. This approach generated a series of elastomers with a tensile strength of over 10 MPa and a laser self-healing efficiency of over 90% within 2 min. In particular, we studied the effects of counterions on the thermodynamic, viscoelastic, mechanical, photothermal, and self-healing properties of the materials. Therefore, this work can provide instruction for the preparation and performance tailoring of metallosupramolecular elastomers.

Fragment-interconnected nitrogen-doped porous carbon nanosheets loaded with platinum group metals for highly boosted hydrogen evolution reaction in alkaline solution.

The rational design and preparation of advanced electrocatalysts for the hydrogen evolution reaction (HER) under alkaline conditions is the key to achieving sustainable hydrogen production. Herein, a new type of nitrogen-doped porous carbon nanosheets (NPCN) loaded with platinum group metals (Pd, Pt or Ru) were prepared. The introduction of melamine not only realized the doping of N-species, but also optimized the morphology and surface functional groups of the prepared catalysts. The prepared Pd-NPCN, Pt-NPCN and Ru-NPCN with a metal loading of about 10 wt% showed outstanding HER activity (21, 9 and 11 mv at 10 mA cm-2 current density), small Tafel slopes (49, 30 and 30 mV dec-1) and good stability in 1.0 M KOH. In addition, the mechanism of the introduction of melamine to improve the catalytic performance of HER was also discussed. Therefore, this work provides promising alternatives to traditional Pt-based catalysts, and is instructive for the design of high-efficiency alkaline HER catalysts.

Ni-O4 as Active Sites for Efficient Oxygen Evolution Reaction with Electronic Metal-Support Interactions.

Precise adjustment of the metal site structure in single-atom catalysts (SACs) plays a key role in addressing the oxygen evolution reaction (OER). Herein, we report the synthesis of O-doped Ni SACs anchored on porous graphene-like carbon (Ni-O-G) using molten salts (ZnCl2 and NaCl) as templates, in which the unique Ni-O4 structure serves as the active sites. Ni-O-G, with an overpotential of only 238 mV (@ 10 mA cm-2), is one of the more advanced catalysts. An array of characterizations and density functional theory calculations show that the Ni-O4 coordination enables Ni to be closer to the Fermi level compared to traditional Ni-N4, enhancing the electronic metal-support interaction to facilitate OER kinetics. Thus, this work offers an alternative strategy for the structural modulation of Ni SACs and the effect of different coordination elements with the same atomic coordination structure on the intrinsic OER activity.

Innovative immune mechanisms and antioxidative therapies of intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is the basic pathological process of many degenerative diseases of the spine, characterized by series of symptoms, among which low back pain (LBP) is the most common symptom that patients suffer a lot, which not only makes patients and individual families bear a huge pain and psychological burden, but also consumes a lot of medical resources. IDD is usually thought to be relevant with various factors such as genetic predisposition, trauma and aging, and IDD progression is tightly relevant with structural and functional alterations. IDD processes are caused by series of pathological processes, including oxidative stress, matrix decomposition, inflammatory reaction, apoptosis, abnormal proliferation, cell senescence, autophagy as well as sepsis process, among which the oxidative stress and inflammatory response are considered as key link in IDD. The production and clearance of ROS are tightly connected with oxidative stress, which would further simulate various signaling pathways. The phenotype of disc cells could change from matrix anabolism-to matrix catabolism- and proinflammatory-phenotype during IDD. Recent decades, with the relevant reports about oxidative stress and inflammatory response in IDD increasing gradually, the mechanisms researches have attracted much more attention. Consequently, this study focused on the indispensable roles of the oxidative stress and inflammatory response (especially macrophages and cytokines) to illustrate the origin, development, and deterioration of IDD, aiming to provide novel insights in the molecular mechanisms as well as significant clinical values for IDD.

Microflora for improving the Auricularia auricula spent mushroom substrate for Protaetia brevitarsis production.

Mushroom cultivation is a sustainable agricultural waste utilization method, but the lack of high-value utilization of the produced spent mushroom substrate (SMS) has hindered the development of mushroom cultivation-based circular agricultural systems. Conversion and utilization of SMS via Protaetia brevitarsis larvae (PBL) have proven to be a high-value AASMS utilization strategy. However, Auricularia auricula SMS (AASMS), which contains woodchips, is less palatable and digestible for PBL. To solve this problem, in this investigation, we screened out microflora (MF) for AASMS fermentation by comparing the fermentation performance as well as the effect on PBL feed intake, weight gain, and AASMS phytotoxic compound removal efficiency. In addition, by bacterial community analysis, the genera Luteimonas, Moheibacter, and Pseudoxanthomonas were predicted to be functional bacteria for AASMS fermentation and contribute to palatability and digestibility improvement.

High-Throughput Sequencing Reveals CXCR4 and IGF1 Behave Different Roles in Weightlessness Osteoporosis.

Objective: This study is aimed at screening the differential expression profiles of mRNA under weightlessness osteoporosis through high-throughput sequencing technology, as well as investigating the pathogenesis of weightlessness osteoporosis at the molecular level especially in bone marrow mesenchymal stem cells (BMSCs). Methods: The mouse bone marrow mesenchymal stem cell line was divided into ground group and simulated microgravity (SMG) group. BMP-2 was used to induce osteogenic differentiation, and SMG group was placed into 2D-gyroscope to simulate weightless condition. Transcriptome sequencing was performed by Illumina technology, DEGs between ground and SMG group was conducted using the DEseq2 algorithm. Molecular functions and signaling pathways enriched by DEGs were then comprehensively analyzed via multiple bioinformatic approaches including but not limited to GO, KEGG, GSEA, and PPI analysis. Results: A total of 263 DEGs were identified by comparing these 2 groups, including 186 upregulated genes and 77 downregulated genes. GO analysis showed that DEGs were enriched in osteoblasts, osteoclasts cell proliferation, differentiation, and apoptosis; KEGG analysis revealed that DEGs were significantly enriched in the TNF signaling pathway and FoxO signaling pathway; the enrichment results from Reactome database displayed that DEGs were mainly involved in the transcription of Hoxb3 gene, RUNX1 recruitment KMT2A gene, and activation of Hoxa2 chromatin signaling pathway. The four genes, IL6, CXCR4, IGF1, and PLOD2, were identified as hub genes for subsequent analysis. Conclusions: This study elucidated the significance of 10 hub genes in the development of weightlessness osteoporosis. In addition, the results of this study provide a theoretical basis and novel ideas for the subsequent research of the pathogenesis and clinical treatment of weightlessness osteoporosis.

The Roles of Blood Lipid-Metabolism Genes in Immune Infiltration Could Promote the Development of IDD.

Objectives: Intervertebral disc degeneration is a progressive and chronic disease, usually manifesting as low back pain. This study aimed to screen effective biomarkers for medical practice as well as figuring out immune infiltration situations between circulation and intervertebral discs. Methods: Gene expression profiles of GSE124272 was included for differentially analysis, WGCNA and immune infiltration analysis from GEO database, and other GSE series were used as validation datasets. A series of validation methods were conducted to verify the robustness of hub genes, such as principal component analysis, machine learning models, and expression verification. Lastly, nomogram was established for medical practice. Results: 10 genes were commonly screened via combination of DEGs, WGCNA analysis and lipid metabolism related genes. Furthermore, 3 hub gens CYP27A1, FAR2, CYP1B1 were chosen for subsequent analysis based on validation of different methods. GSEA analysis discovered that neutrophil extracellular traps formation and NOD-like receptor signaling pathway was activated during IDD. Immune infiltration analysis demonstrated that the imbalance of neutrophils and γδT cells were significantly correlated with IDD progression. Nomogram was established based on CYP27A1, FAR2, CYP1B1 and age, the calibration plot confirmed the stability of our model. Conclusion: CYP27A1, FAR2, CYP1B1 were considered as hub lipid metabolism related genes (LMRGs) in the development of IDD, which were regarded as candidate diagnostic biomarkers especially in circulation. The effects are worth expected in the early diagnosis of IDD through detecting these genes in blood.