Gradient gyroid Ti6Al4V scaffolds with TiO2 surface modification: Promising approach for large bone defect repair.

Large bone defects, particularly those exceeding the critical size, present a clinical challenge due to the limited regenerative capacity of bone tissue. Traditional treatments like autografts and allografts are constrained by donor availability, immune rejection, and mechanical performance. This study aimed to develop an effective solution by designing gradient gyroid scaffolds with titania (TiO2) surface modification for the repair of large segmental bone defects. The scaffolds were engineered to balance mechanical strength with the necessary internal space to promote new bone formation and nutrient exchange. A gradient design of the scaffold was optimized through Finite Element Analysis (FEA) and Computational Fluid Dynamics (CFD) simulations to enhance fluid flow and cell adhesion. In vivo studies in rabbits demonstrated that the G@TiO2 scaffold, featuring a gradient structure and TiO2 surface modification, exhibited superior healing capabilities compared to the homogeneous structure and TiO2 surface modification (H@TiO2) and gradient structure (G) scaffolds. At 12 weeks post-operation, in a bone defect representing nearly 30 % of the total length of the radius, the implantation of the G@TiO2 scaffold achieved a 27 % bone volume to tissue volume (BV/TV) ratio, demonstrating excellent osseointegration. The TiO2 surface modification provided photothermal antibacterial effects, enhancing the scaffold's biocompatibility and potential for infection prevention. These findings suggest that the gradient gyroid scaffold with TiO2 surface modification is a promising candidate for treating large segmental bone defects, offering a combination of mechanical strength, bioactivity, and infection resistance.

The bone nonunion microenvironment: A place where osteogenesis struggles with osteoclastic capacity.

Bone nonunion is a common and serious orthopedic disorder, the occurrence of which is associated with a disruption of the dynamic balance between osteoblasts and osteoclasts during bone repair. However, the critical molecular mechanisms affecting this homeostasis are not well understood, and it is essential to investigate the specific components of this mechanism and to restore the balance between osteoblasts and osteoclasts to promote bone repair. First, we defined this complex local environmental factor as the "bone nonunion microenvironment" and identified the importance of the "struggle" between osteoblasts and osteoclasts, which is the most essential element in determining the process of repair. On this basis, we also explored the cellular factors that influence osteogenesis and the molecular signals that influence the balance between osteoclast and osteoblasts, which are important for restoring homeostasis. Further, we explored other factors involved in osteogenesis, such as the biomechanical environment, the nutritional environment, the acid-base environment, and the temperature environment, which are important players in osteogenesis. In conclusion, we found that the balance between osteoblasts and osteoclasts is the essence of bone healing, which is based on the "bone nonunion microenvironment". Therefore, investigating the role of the bone nonunion microenvironment in the system of osteoblast-osteoclast "struggle" provides an important basis for further understanding of the mechanism of nonunion and the development of new therapeutic approaches.

Spinel Nanostructures for the Hydrogenation of CO2 to Methanol and Hydrocarbon Chemicals.

Composite oxides have been widely applied in the hydrogenation of CO/CO2 to methanol or as the component of bifunctional oxide-zeolite for the synthesis of hydrocarbon chemicals. However, it is still challenging to disentangle the stepwise formation mechanism of CH3OH at working conditions and selectively convert CO2 to hydrocarbon chemicals with narrow distribution. Here, we investigate the reaction network of the hydrogenation of CO2 to methanol over a series of spinel oxides (AB2O4), among which the Zn-based nanostructures offer superior performance in methanol synthesis. Through a series of (quasi) in situ spectroscopic characterizations, we evidence that the dissociation of H2 tends to follow a heterolytic pathway and that hydrogenation ability can be regulated by the combination of Zn with Ga or Al. The coordinatively unsaturated metal sites over ZnAl2Ox and ZnGa2Ox originating from oxygen vacancies (OVs) are evidenced to be responsible for the dissociative adsorption and activation of CO2. The evolution of the reaction intermediates, including both carbonaceous and hydrogen species at high temperatures and pressures over the spinel oxides, has been experimentally elaborated at the atomic level. With the integration of a series of zeolites or zeotypes, high selectivities of hydrocarbon chemicals with narrow distributions can be directly produced from CO2 and H2, offering a promising route for CO2 utilization.

Suillusgrevillei and Suillus luteus promote lead tolerance of Pinus tabulaeformis and biomineralize lead to pyromorphite.

Lead (Pb) is a hazardous heavy metal that accumulates in many environments. Phytoremediation of Pb polluted soil is an environmentally friendly method, and a better understanding of mycorrhizal symbiosis under Pb stress can promote its efficiency and application. This study aims to evaluate the impact of two ectomycorrhizal fungi (Suillus grevillei and Suillus luteus) on the performance of Pinus tabulaeformis under Pb stress, and the biomineralization of metallic Pb in vitro. A pot experiment using substrate with 0 and 1,000 mg/kg Pb2+ was conducted to evaluate the growth, photosynthetic pigments, oxidative damage, and Pb accumulation of P. tabulaeformis with or without ectomycorrhizal fungi. In vitro co-cultivation of ectomycorrhizal fungi and Pb shots was used to evaluate Pb biomineralization. The results showed that colonization by the two ectomycorrhizal fungi promoted plant growth, increased the content of photosynthetic pigments, reduced oxidative damage, and caused massive accumulation of Pb in plant roots. The structural characteristics of the Pb secondary minerals formed in the presence of fungi demonstrated significant differences from the minerals formed in the control plates and these minerals were identified as pyromorphite (Pb5(PO4)3Cl). Ectomycorrhizal fungi promoted the performance of P. tabulaeformis under Pb stress and suggested a potential role of mycorrhizal symbiosis in Pb phytoremediation. This observation also represents the first discovery of such Pb biomineralization induced by ectomycorrhizal fungi. Ectomycorrhizal fungi induced Pb biomineralization is also relevant to the phytostabilization and new approaches in the bioremediation of polluted environments.

Enhancing the sequence coverage of nanodiamond-extracted early secretory proteins from the Mycobacterium tuberculosis complex.

The unambiguous identification of protein species requires high sequence coverage. In this study, we successfully improved the sequence coverage of early secretory 10 kDa cell filtrate protein (CFP-10) and 6 kDa early secretory antigenic target (ESAT-6) proteins from the Mycobacterium tuberculosis complex (MTC) in broth culture media with the use of the 4-chloro-α-cyanocinnamic acid (Cl-CCA) matrix. Conventional matrices, α-cyano-hydroxy-cinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB), were also used for comparison. After nanodiamond (ND) extraction, the sequence coverage of the CFP-10 protein was 87% when CHCA and DHB matrices were used, and the ESAT-6 protein was not detected. On the other hand, the sequence coverage for ND-extracted CFP-10 and ESAT-6 could reach 94% and 100%, respectively, when the Cl-CCA matrix was used and with the removal of interference from bovine serum albumin (BSA) protein and α-crystallin (ACR) protein. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) was also adopted to analyze the protein mass spectra. A total of 6 prominent ion signals were observed, including ESAT-6 protein peaks at mass-to-charge ratios (m/z) of ∼7931, ∼7974, ∼9768, and ∼9813 and CFP-10 protein peaks at m/z of ∼10 100 and ∼10 660. The ESAT-6 ion signals were always detected concurrently with CFP-10 ion signals, but CFP-10 ion signals could be detected alone without the ESAT-6 ion signals. Furthermore, the newly found ESAT-6 peaks were also confirmed using a Mag-Beads-Protein G kit with an ESAT-6 antibody to capture the ESAT-6 protein, which was also consistent with the sequence coverage analysis.

Exploration of the mode of death and potential death mechanisms of nucleus pulposus cells.

Intervertebral disc degeneration (IVDD) is a common chronic orthopaedic disease in orthopaedics that imposes a heavy economic burden on people and society. Although it is well established that IVDD is associated with genetic susceptibility, ageing and obesity, its pathogenesis remains incompletely understood. Previously, IVDD was thought to occur because of excessive mechanical loading leading to destruction of nucleus pulposus cells (NPCs), but studies have shown that IVDD is a much more complex process associated with inflammation, metabolic factors and NPCs death and can involve all parts of the disc, characterized by causing NPCs death and extracellular matrix (ECM) degradation. The damage pattern of NPCs in IVDD is like that of some programmed cell death, suggesting that IVDD is associated with programmed cell death. Although apoptosis and pyroptosis of NPCs have been studied in IVDD, the pathogenesis of intervertebral disc degeneration can still not be fully elucidated by using only traditional cell death modalities. With increasing research, some new modes of cell death, PANoptosis, ferroptosis and senescence have been found to be closely related to intervertebral disc degeneration. Among these, PANoptosis combines essential elements of pyroptosis, apoptosis and necroptosis to form a highly coordinated and dynamically balanced programmed inflammatory cell death process. Furthermore, we believe that PANoptosis may also crosstalk with pyroptosis and senescence. Therefore, we review the progress of research on multiple deaths of NPCs in IVDD to provide guidance for clinical treatment.

Dual substitution of host lattice ions to enhance the luminescence properties of Zn2TiO4:Cr3+ phosphor.

Near-infrared light sources have potential applications in many fields. Cr3+ is a good luminescence centre to prepare near-infrared phosphors. Improving the performance of existing near-infrared luminescent materials has indeed attracted great interest from researchers. The luminescence properties of Zn2TiO4:Cr3+ were improved by crystal field engineering strategies. Zn2+-Ti4+ was partially replaced using a Li+-Nb5+ ion pair based on the Zn2TiO4:Cr3+ phosphors. Luminescence Cr3+-activated luminescent materials are sensitive to changes in the local crystal structure and crystal field environment. Doping of Li+-Nb5+ increased the luminescence intensity up to 2.7 times that of the undoped sample. Also, the thermal stability of the phosphor was greatly increased by the replacement of Li+-Nb5+.

UBD participates in neutrophilic asthma by promoting the activation of IL-17 signaling.

Neutrophilic asthma is a persistent and severe inflammatory lung disease characterized by neutrophil activation and the mechanisms of which are not completely elucidated. Ubiquitin D (UBD) is a ubiquitin-like modifier participating in infections, immune responses, and tumorigenesis, while whether UBD involves in neutrophilic asthma needs further study. In this study, we initially found that UBD expression was significantly elevated and interleukin 17 (IL-17) signaling was enriched in the endobronchial biopsies of severe asthma along with neutrophils increasing by bioinformatics analysis. We further confirmed that UBD was upregulated in the lung tissues of neutrophilic asthma mouse model. UBD overexpression promoted IL-17 signaling activation. Knockdown of UBD suppressed the activation of IL-17 signaling. UBD interacted with TRAF2 and reduced the total and the K48-linked ubiquitination of TRAF2. However, IL-17 A stimulation increased both the total and the K48-linked ubiquitination of TRAF2. Together, these findings indicated that UBD was upregulated and played a critical role in IL-17 signaling which contributed to a better understanding of the complex mechanisms in neutrophilic asthma.

Stable anchoring of single rhodium atoms by indium in zeolite alkane dehydrogenation catalysts.

Maintaining the stability of single-atom catalysts in high-temperature reactions remains extremely challenging because of the migration of metal atoms under these conditions. We present a strategy for designing stable single-atom catalysts by harnessing a second metal to anchor the noble metal atom inside zeolite channels. A single-atom rhodium-indium cluster catalyst is formed inside zeolite silicalite-1 through in situ migration of indium during alkane dehydrogenation. This catalyst demonstrates exceptional stability against coke formation for 5500 hours in continuous pure propane dehydrogenation with 99% propylene selectivity and propane conversions close to the thermodynamic equilibrium value at 550°C. Our catalyst also operated stably at 600°C, offering propane conversions of >60% and propylene selectivity of >95%.

Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability.

Epimedin B (EB) is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim., a traditional herb widely used in China. Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase (TYR). However, the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear. Herein, as an extension to our previous investigation, we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins (TYRs) in terms of expression, activity, and stability. The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt (referred to as protein kinase B (PKB))/glycogen synthase kinase 3ß (GSK3ß)/ß-catenin, p-p70 S6 kinase cascades, and protein 38 (p38)/mitogen-activated protein (MAP) kinase (MAPK) and extracellular regulated protein kinases (ERK)/MAPK pathways, after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues. Furthermore, EB exerted repigmentation by stimulating TYR activity in hydroquinone- and N-phenylthiourea-induced TYR inhibitive models, including melanoma cells, zebrafish, and mice. Finally, EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding, TYR-related protein 1 formation, and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes. These data conclude that EB can target TYRs and alter their expression, activity, and stability, thus stimulating their pigmentation function, which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.

Selectivity Control by Relay Catalysis in CO and CO2 Hydrogenation to Multicarbon Compounds.

ConspectusThe hydrogenative conversion of both CO and CO2 into high-value multicarbon (C2+) compounds, such as olefins, aromatic hydrocarbons, ethanol, and liquid fuels, has attracted much recent attention. The hydrogenation of CO is related to the chemical utilization of various carbon resources including shale gas, biomass, coal, and carbon-containing wastes via syngas (a mixture of H2 and CO), while the hydrogenation of CO2 by green H2 to chemicals and liquid fuels would contribute to recycling CO2 for carbon neutrality. The state-of-the-art technologies for the hydrogenation of CO/CO2 to C2+ compounds primarily rely on a direct route via Fischer-Tropsch (FT) synthesis and an indirect route via two methanol-mediated processes, i.e., methanol synthesis from CO/CO2 and methanol to C2+ compounds. The direct route would be more energy- and cost-efficient owing to the reduced operation units, but the product selectivity of the direct route via FT synthesis is limited by the Anderson-Schulz-Flory (ASF) distribution. Selectivity control for the direct hydrogenation of CO/CO2 to a high-value C2+ compound is one of the most challenging goals in the field of C1 chemistry, i.e., chemistry for the transformation of one-carbon (C1) molecules.We have developed a relay-catalysis strategy to solve the selectivity challenge arising from the complicated reaction network in the hydrogenation of CO/CO2 to C2+ compounds involving multiple intermediates and reaction channels, which inevitably lead to side reactions and byproducts over a conventional heterogeneous catalyst. The core of relay catalysis is to design a single tandem-reaction channel, which can direct the reaction to the target product controllably, by choosing appropriate intermediates (or intermediate products) and reaction steps connecting these intermediates, and arranging optimized yet matched catalysts to implement these steps like a relay. This Account showcases representative relay-catalysis systems developed by our group in the past decade for the synthesis of liquid fuels, lower (C2-C4) olefins, aromatics, and C2+ oxygenates from CO/CO2 with selectivity breaking the limitation of conventional catalysts. These relay systems are typically composed of a metal or metal oxide for CO/CO2/H2 activation and a zeolite for C-C coupling or reconstruction, as well as a third or even a fourth catalyst component with other functions if necessary. The mechanisms for the activation of H2 and CO/CO2 on metal oxides, which are distinct from that on the conventional transition or noble metal surfaces, are discussed with emphasis on the role of oxygen vacancies. Zeolites catalyze the conversion of intermediates (including hydrocracking/isomerization of heavier hydrocarbons, methanol-to-hydrocarbon reactions, and carbonylation of methanol/dimethyl ether) in the relay system, and the selectivity is mainly controlled by the Brønsted acidity and the shape-selectivity or the confinement effect of zeolites. We demonstrate that the thermodynamic/kinetic matching of the relay steps, the proximity and spatial arrangement of the catalyst components, and the transportation of intermediates/products in sequence are the key issues guiding the selection of each catalyst component and the construction of an efficient relay-catalysis system. Our methodology would also be useful for the transformation of other C1 molecules via controlled C-C coupling, inspiring more efforts toward precision catalysis.

Red mud accommodated mesoporous black TiO2 framework with enhanced organic pollutant photodegradation.

In this work, black TiO2 (BTiO2) loaded on black red mud (BRM) was successfully prepared with the conversion of Fe2O3 into magnetic Fe3O4 in red mud and the reduction of partial Ti4+ to Ti3+ in TiO2 via the facile sol-gel method and H2 reduction treatment. The obtained low-cost BRM/BTiO2 composites exhibit remarkable photocatalytic degradation toward rhodamine B (91.2%) and tetracycline (83.6%) under visible light irradiation, much better than pristine TiO2. This enhancement is attributed to the narrow bandgap with the desired solar-light excitation, the black color with good solar-light absorption, and the heterojunctions with the efficient separation of photogenerated electron-hole pairs. Moreover, the desired magnetic separation of BRM/BTiO2 composites realizes the recycle and recovery of photocatalysts, favoring practical applications in environment. This work provides a cost-efficiency way to prepare RM-supported TiO2 composites for treating organic pollutants in the wastewater, which is of great significance to the comprehensive utilization of RM waste, the cost saving of the photocatalyst, and the visible-light active enhancement of TiO2.

Fabrication of Metal-Organic Framework-Based Mixed-Matrix Membranes by "Soft Spray" Technique.

Metal-organic framework (MOF)-based mixed-matrix membranes (MMMs) represent a class of composite membranes that seamlessly integrate the properties of MOF fillers and polymer matrix into a hybrid system and have been widely used in countless advanced technologies. However, there remains a need for scalable and simple manufacturing techniques that can fabricate a MOF-based MMM with uniform dispersion. Herein, a series of MMMs with well-dispersed MOFs are constructed by a soft spray technique. In brief, by uniformly spraying metal ions onto the surface of a mixed solution containing polyvinylpyrrolidone (PVP) and organic ligands, a free-standing MMM is synthesized at the miscible liquid-liquid interface, facilitated by the dual function of metal ions. Moreover, soft spray technology can also introduce multifunctional materials into the MMM to customize performance. We have successfully introduced carbon black into a MOF-based MMM by soft spray, resulting in MMMs with excellent photothermal effects. The resulted MOF-based MMM exhibits favorable catalytic performance in the condensation reaction of benzaldehyde with primary amines, and the MOF-based MMM modified with carbon black significantly boosts the endothermic CO2 conversion. The work opens a new avenue for the development of MOF-based MMMs with a promising future.

Bioinformatics-based discovery of intervertebral disc degeneration biomarkers and immune-inflammatory infiltrates.

Background: Intervertebral disc degeneration (IVDD) is a common chronic disease in orthopedics, and its molecular mechanisms are still not well explained. Aim: This study's objective was to bioinformatics-based discovery of IVDD biomarkers and immune-inflammatory infiltrates. Materials and Methods: The IVDD illness gene collection was gathered from GeneCards, DisGeNet, and gene expression profiles were chosen from the extensive Gene Expression Omnibus database (GSE124272, GSE150408, and GSE153761). The STRING database was used to create a network of protein-protein interactions, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases were used for functional enrichment analysis. Using hub genes, the immune cell infiltration between IVDD patient samples and control tissues was examined. Finally, quantitative polymerase chain reaction and Western blot experiments were used to verify the expression of hub genes. Results: A total of 27 differentially expressed hub genes were identified by bioinformatics. According to GO and KEGG analyses, hub genes were prominent in immunological responses, chemokine-mediated signaling pathways, and inflammatory responses, with the key signaling pathways engaged in cellular senescence, apoptosis, Th1 and Th2 cell differentiation, and Th17 cell differentiation. Immune cell infiltration research revealed that T cells, lymphocytes, B cells, and NK cells were decreased in IVDD patients while monocytes, neutrophils, and CD8 T cells were increased. The expression levels of the senescence hub genes SP1, VEGFA, IL-6, and the apoptosis key gene CASP3 were considerably greater in the IVDD model group than in the control group, according to in vitro validation. Conclusion: In conclusion, the cellular senescence signaling pathway, the apoptosis signaling pathway, and associated hub genes play significant roles in the development and progression of IVDD, this finding may help direct future research on the senescence signaling route in IVDD.

A Compound Essential Oil Alters Stratum Corneum Structure, Potentially Promoting the Transdermal Permeation of Hydrophobic and Hydrophilic Ingredients.

BACKGROUND: The stratum corneum (SC) is the main barrier of the skin, and cosmeceuticals are different from ordinary cosmetics in that they need to deliver active ingredients targeting specific skin problems through the SC into the deeper layers of the skin. Thus, we designed a compound essential oil (CEO) extracted from Salvia miltiorrhiza Bge and Cinnamomum cassia Presl, supplemented with borneol to deliver active ingredients through the SC. METHODS: The CEO was prepared by flash extraction combined with the microwave method. Moreover, the main components of the CEO were determined using gas chromatography-mass spectrometry (GCMS). Visualization techniques, such as scanning electron microscopy (SEM), haematoxylin-eosin (HE) staining, and confocal laser scanning microscopy (CLSM), were used to study the permeationpromoting mechanism of the CEO on the skin. Furthermore, the permeation-promoting effects of the CEO on both hydrophobic and hydrophilic ingredients were tested via in vitro skin penetration experiments and in vivo microdialysis experiments. RESULTS: The results indicated the ability of the CEO to alter the structure of the SC, leading to enhanced transdermal permeation of hydrophobic and hydrophilic ingredients. The 1.5% CEO group demonstrated the best permeation-promoting effect compared to the other CEO groups and blank groups (P<0.05). Furthermore, the CEO displayed an expedited permeability-promoting effect on hydrophobic ingredients compared to hydrophilic ingredients. CONCLUSION: It is concluded that the prepared CEO can promote the transdermal permeation of hydrophobic and hydrophilic ingredients. This study will provide a reference for the application of the prepared CEO in the development of cosmeceuticals with natural efficacy.

Crystal structure and luminescence properties of a novel near-infrared phosphor LiAlO2:Fe3.

Cr3+-free near-infrared (NIR) phosphors are currently gaining significant attention in various application fields. A novel Fe3+-activated LiAlO2 NIR phosphor was successfully synthesized by high-temperature solid-state method. Under excitation of 391 nm and 467 nm, the phosphor emits near-infrared light with wavelengths ranging from 600 to 850 nm. The emission bands with peaks at 725 nm correspond to the transition from 4T1(4G) to the ground state energy level 6A1(6S). The optical band gap of LiAlO2 was calculated using Density Function Theory (DFT) and diffuse reflectance spectrum, respectively. The thermal stability of the sample was measured under 391 nm and 467 nm excitation, showing that the emission intensity at 413 K is 55.3 % and 52.4 % of the emission intensity at room temperature.

A Novel Kunitz-Type Serine Protease Inhibitor (HcKuSPI) is Involved in Antibacterial Defense in Innate Immunity and Participates in Shell Formation of Hyriopsis cumingii.

Serine protease inhibitors (SPIs) are abundantly reported for its inhibition against specific proteases involved in the immune responses, but SPI data related to calcareous shells are scarce. Previously, our research group has reported the proteome analysis of non-nucleated pearl powder, and a candidate matrix protein containing two Kunitz domains in the acid soluble fraction caught our attention. In the present study, the full-length cDNA sequence of HcKuSPI was obtained from Hyriopsis cumingii. HcKuSPI was specifically expressed in the mantle, with hybridization signals mainly concentrated to dorsal epithelial cells at the mantle edge and weak signals at the mantle pallium, suggesting HcKuSPI was involved in shell formation. HcKuSPI expression in the mantle was upregulated after Aeromonas hydrophila and Staphylococcus aureus challenge to extrapallial fluids (EPFs). A glutathione S transferase (GST)-HcKuSPI recombinant protein showed strong inhibitory activity against the proteases, trypsin and chymotrypsin. Moreover, HcKuSPI expression in an experimental group was significantly higher when compared with a control group during pellicle growth and crystal deposition in shell regeneration processes, while the organic shell framework of newborn prisms and nacre tablets was completely destroyed after HcKuSPI RNA interference (RNAi). Therefore, HcKuSPI secreted by the mantle may effectively neutralize excess proteases and bacterial proteases in the EPF during bacterial infection and could prevent matrix protein extracellular degradation by suppressing protease proteolytic activity, thereby ensuring a smooth shell biomineralization. In addition, GST-HcKuSPI was also crucial for crystal morphology regulation. These results have important implications for our understanding of the potential roles of SPIs during shell biomineralization.

Exploring the potential mechanism of Taohong Siwu decoction in the treatment of avascular necrosis of the femoral head based on network pharmacology and molecular docking.

Based on network pharmacology and molecular docking, this study seeks to investigate the mechanism of Taohong Siwu decoction (THSWD) in the treatment of avascular necrosis of the femoral head (AVNFH). The Traditional Chinese Medicine Systems Pharmacology database was used in this investigation to obtain the active ingredients and related targets for each pharmaceutical constituent in THSWD. To find disease-related targets, the terms "avascular necrosis of the femoral head," "necrosis of the femoral head," "steroid-induced necrosis of the femoral head," "osteonecrosis," and "avascular necrosis of the bone" were searched in the databases DisGeNET, GeneCards, Comparative Toxicogenomics Database, and MalaCards. Following the identification of the overlap targets of THSWD and AVNFH, enrichment analysis using gene ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and WikiPathways was conducted. The "THSWD-drug-active compound-intersection gene-hub gene-AVNFH" network and protein-protein interaction network were built using Cytoscape 3.9.1 and string, and CytoHubba was used to screen hub genes. The binding activities of hub gene targets and key components were confirmed by molecular docking. 152 prospective therapeutic gene targets were found in the bioinformatics study of ONFH treated with THSWD, including 38 major gene targets and 10 hub gene targets. The enrichment analysis of 38 key therapeutic targets showed that the biological process of gene ontology analysis mainly involved cytokine-mediated signaling pathway, angiogenesis, cellular response to reactive oxygen species, death-inducing signaling complex. The Kyoto Encyclopedia of Genes and Genomes signaling pathway mainly involves TNF signaling pathway, IL-17 signaling pathway, and the Recactome pathway mainly involves Signaling by Interleukins, Apoptosis, and Intrinsic Pathway for Apoptosis. WikiPathways signaling pathway mainly involves TNF-related weak inducer of apoptosis signaling pathway, IL-18 signaling pathway. According to the findings of enrichment analysis, THSWD cured AVNFH by regulating angiogenesis, cellular hypoxia, inflammation, senescence, apoptosis, cytokines, and cellular proliferation through the aforementioned targets and signaling pathways. The primary component of THSWD exhibits a strong binding force with the key protein of AVNFH. This study sheds new light on the biological mechanism of THSWD in treating AVNFH by revealing the multi-component, multi-target, and multi-pathway features and molecular docking mechanism of THSWD.

Factors Influencing a Favorable Outcome for RFA of Huge Benign Thyroid Nodules: Preliminary Results and Short-Term Evaluation.

Objective: This study aimed to investigate potentially favorable factors influencing the therapeutic success of radiofrequency ablation (RFA) of huge benign thyroid nodules (BTNs) (volume >100 ml) and to evaluate the feasibility of RFA as an alternative treatment modality for patients unable or unwilling to undergo surgery. Methods: This retrospective study evaluated a total of 868 patients, of which 22 patients had huge BTNs who underwent ultrasound-guided moving shot RFA treatment between May 2017 and January 2022. The huge BTNs were categorized into two groups according to a post-RFA treatment volume reduction ratio (VRR) of >80% and <80% at 6 months. Factors influencing these huge BTNs were reviewed, analyzed, and correlated with treatment effectiveness between the two groups. Results: The factors influencing an effective VRR included huge BTNs located on the left side (OR 7.875, p = 0.03), predominant solid/spongiform nodules (OR 7.875, p = 0.03), and higher initial ablation rate (IAR) (p = 0.028). Multivariable logistic regression revealed predominant solid/spongiform nodule and the higher IAR were associated with the advanced VRR. Conclusion: RFA was effective at decreasing the volume of huge BTNs with an acceptable complication rate. The BTN characteristics correlated with a better VRR at the 6-month short-term follow-up were predominant solid/spongiform BTNs and those with the first time ablation treatment initial ablation rate. Nevertheless, regarding the higher regrowth rate of these groups of patients who may need to be treated more times, RFA can only be a feasible alternative treatment modality for patients unable or unwilling to undergo operation.

Circular RNA (circ)_0053277 Contributes to Colorectal Cancer Cell Growth, Angiogenesis, Metastasis and Glycolysis.

Circular RNAs (circRNAs) have been found to be abnormally expressed in many cancers, including colorectal cancer (CRC). Circ_0053277 has been found to mediate CRC malignant processes and may be a key regulator for CRC progression. Therefore, its role and potential molecular mechanism in CRC process deserve further investigation. Quantitative real-time PCR was used to detect the expression levels of circ_0053277, microRNA-520 h (miR-520 h) and hexokinase 1 (HK1). Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, wound healing assay, transwell assay, and tube formation assay were used to detect CRC cell proliferation, apoptosis, migration, invasion, and angiogenesis. The protein levels of apoptosis-related markers and HK1 were detected by western blot. The relationship between circ_0053277 and miR-520 h or miR-520 h and HK1 in CRC cells was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Cell glycolysis was assessed by detecting glucose uptake and lactate production. The effect of silenced circ_0053277 on CRC tumor growth was evaluated by xenograft model in vivo. Our study found that circ_0053277 expression was elevated in CRC tissues and cells. Moreover, circ_0053277 knockdown suppressed CRC cell proliferation, angiogenesis, migration and invasion, while promoting apoptosis. In terms of mechanism, circ_0053277 sponged miR-520 h, and HK1 was the target of miR-520 h. Meanwhile, miR-520 h inhibitor reversed the inhibitory effect of circ_0053277 silencing on CRC cell progression, and HK1 overexpression also overturned the suppressive effect of miR-520 h on CRC cell growth, angiogenesis and metastasis. Moreover, circ_0053277 knockdown inhibited the glycolysis of CRC cells by regulating miR-520 h/HK1 pathway. In addition, knockdown of circ_0053277 reduced CRC tumor growth in vivo. Circ_0053277 promoted CRC cell growth, angiogenesis, metastasis and glycolysis by miR-520 h/HK1 pathway, confirming that circ_0053277 might be a potential clinical target for CRC treatment.