Systematic HOIP interactome profiling reveals critical roles of linear ubiquitination in tissue homeostasis.

Linear ubiquitination catalyzed by HOIL-1-interacting protein (HOIP), the key component of the linear ubiquitination assembly complex, plays fundamental roles in tissue homeostasis by executing domain-specific regulatory functions. However, a proteome-wide analysis of the domain-specific interactome of HOIP across tissues is lacking. Here, we present a comprehensive mass spectrometry-based interactome profiling of four HOIP domains in nine mouse tissues. The interaction dataset provides a high-quality HOIP interactome resource with an average of approximately 90 interactors for each bait per tissue. HOIP tissue interactome presents a systematic understanding of linear ubiquitination functions in each tissue and also shows associations of tissue functions to genetic diseases. HOIP domain interactome characterizes a set of previously undefined linear ubiquitinated substrates and elucidates the cross-talk among HOIP domains in physiological and pathological processes. Moreover, we show that linear ubiquitination of Integrin-linked protein kinase (ILK) decreases focal adhesion formation and promotes the detachment of Shigella flexneri-infected cells. Meanwhile, Hoip deficiency decreases the linear ubiquitination of Smad ubiquitination regulatory factor 1 (SMURF1) and enhances its E3 activity, finally causing a reduced bone mass phenotype in mice. Overall, our work expands the knowledge of HOIP-interacting proteins and provides a platform for further discovery of linear ubiquitination functions in tissue homeostasis.

Aucubin Alleviates Intervertebral Disc Degeneration by Repressing NF-κB-NLRP3 Inflammasome Activation in Endplate Chondrocytes.

Background: Intervertebral disc degeneration (IDD) is a prevalent degenerative disease and often recognized as the primary cause of lower back pain (LBP). Aucubin (Au) is a natural compound with anti-inflammatory properties in various diseases. The present study aimed to confirm the therapeutic effect of Au on IDD and explore its potential mechanism in vivo and in vitro. Methods: The process of IDD was simulated using the lumbar spine instability (LSI) model. In vivo, the therapeutic effect of Au on LSI-induced mice was evaluated by micro-CT and histomorphometry. Additionally, immunohistochemistry was applied to detect the cartilage metabolism and inflammasome activation in endplate. In vitro, the cytotoxicity of Au on ATDC5 cells was detected by Cell Counting Kit-8 (CCK-8), and the biological effects of Au were evaluated by Quantitative Real-time PCR (qRT-PCR) and Western blotting. Results: Micro-CT analysis showed that Au administration significantly alleviated LSI-induced disc volume narrowing and endplate cartilage degeneration, which was further supported by Alcian Blue Hematoxylin/Orange G (ABH/OG) staining. Immunohistochemistry results verified that Au could increase the expression of Col2α1 and Aggrecan, reduce the expression of Mmp-13, and attenuate the degradation of the endplate extracellular matrix (ECM). Mechanistically, we found that Au treatment, both in vivo and in vitro, significantly inhibited NF-κB-NLRP3 inflammasome activation in chondrocytes as determined by the decreased expression of p-P65, NLRP3, and Caspase-1. Discussion: Taken together, our findings have demonstrated for the first time that Au treatment ameliorated the degeneration of cartilage endplates in IDD may by inhibiting NF-κB-NLRP3 inflammasome activation in chondrocytes and provided a potential candidate for the treatment of IDD.

Designing Intelligent Nanomaterials to Achieve Highly Sensitive Diagnoses and Multimodality Therapy of Bladder Cancer.

Bladder cancer (BC) is among the most common malignant tumors of the genitourinary system worldwide. In recent years, the rate of BC incidence has increased, and the recurrence rate is high, resulting in poor quality of life for patients. Therefore, how to develop an effective method to achieve synchronous precise diagnoses and BC therapies is a difficult problem to solve clinically. Previous reports usually focus on the role of nanomaterials as drug delivery carriers, while a summary of the functional design and application of nanomaterials is lacking. Summarizing the application of functional nanomaterials in high-sensitivity diagnosis and multimodality therapy of BC is urgently needed. This review summarizes the application of nanotechnology in BC diagnosis, including the application of nanotechnology in the sensoring of BC biomarkers and their role in monitoring BC. In addition, conventional and combination therapies strategy in potential BC therapy are analyzed. Moreover, different kinds of nanomaterials in BC multimodal therapy according to pathological features of BC are also outlined. The goal of this review is to present an overview of the application of nanomaterials in the theranostics of BC to provide guidance for the application of functional nanomaterials to precisely diagnose and treat BC.

Accurate diagnosis of prostate cancer with CRISPR-based nucleic acid test strip by simultaneously identifying PCA3 and KLK3 genes.

Although serum prostate specific antigen (PSA) testing could decrease the morality of prostate cancer (PCa), its low specificity usually led to misdiagnosis due to prostatitis or benign prostatic hyperplasia (BPH). Prostate cancer antigen 3 (PCA3) as an alternative prostate tumor-specificity biomarker could be used to increase the specificity of PCa diagnosis, however, it usually required sophisticated operation and expensive equipment for routine detection. Herein, we constructed an early detection platform for prostate cancer with reverse transcriptase-recombinase aided amplification (RT-RAA) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 based nucleic acid test strip. The amplicons of PCA3 and kallikrein related peptidase 3 (KLK3) gene, which amplified simultaneously by single-amplification unit of RT-RAA were specifically recognized by Cas9-sgRNA and visual on the nucleic acid test strip by naked eyes without instruments. Simultaneously detection of PCA3 and KLK3 gene could improve specificity and accuracy of the diagnosis but avoid mutual interference. In addition, the platform presented a detection limit of 500 fg/µL and 50 fg/µL in PCA3 and KLK3 gene, respectively. Furthermore, the analysis result of signal ratio of PCA3 to KLK3 gene of urine and peripheral blood specimens from 32 men with suspected prostate cancer on test strips illustrated that the area under the curve values of urine and peripheral blood specimens were 0.998 and 1.0 respectively. In summary, our study highlighted a facile strategy to design an accurate prostate cancer gene detection platform which had the potential to conduct prostate cancer early detection in the resource-limited or other point-of-care testing (POCT) environments.

Cerium oxide-based nanozyme suppresses kidney calcium oxalate crystal depositions via reversing hyperoxaluria-induced oxidative stress damage.

Oxidative stress damage to renal epithelial cells is the main pathological factor of calcium oxalate calculi formation. The development of medicine that could alleviate oxidative damage has become the key to the prevention and treatment of urolithiasis. Herein, porous nanorods CeO2 nanoparticles (CNPs) were selected from CeO2 with different morphologies as an antioxidant reagent to suppress kidney calcium oxalate crystal depositions with excellent oxidation resistance due to its larger specific surface area. The reversible transformation from Ce3+ to Ce4+ could catalyze the decomposition of excess free radicals and act as a biological antioxidant enzyme basing on its strong ability to scavenge free radicals. The protection capability of CNPS against oxalate-induced damage and the effect of CNPS on calcium oxalate crystallization were studied. CNPS could effectively reduce reactive oxygen species production, restore mitochondrial membrane potential polarity, recover cell cycle progression, reduce cell death, and inhibit the formation of calcium oxalate crystals on the cell surface in vitro. The results of high-throughput sequencing of mRNA showed that CNPs could protect renal epithelial cells from oxidative stress damage caused by high oxalate by suppressing the expression gene of cell surface adhesion proteins. In addition, CNPS can significantly reduce the pathological damage of renal tubules and inhibit the deposition of calcium oxalate crystals in rat kidneys while having no significant side effect on other organs and physiological indicators in vivo. Our results provide a new strategy for CNPS as a potential for clinical prevention of crystalline kidney injury and crystal deposition.

Case Report: A case of HNF1B mutation patient with first presentation of diabetic ketosis.

Background: Maturity-onset diabetes of the young 5 (MODY5), a rare diabetes syndrome of young adults, is associated with variants in hepatocyte nuclear factor 1B (HNF1B) gene. Case Presentation: We reported a case of MODY5, which presented with diabetic ketosis, multiple renal cysts, and hypokalemia. In this case, the HNF1B score was estimated as 13 and a heterozygous variant of HNF1B in exon 4 (c.826C>T, p.Arg276*) was identified through Sanger sequencing. Conclusions: Multiple renal cysts and youth-onset diabetes are common manifestations in patients with HNF1B mutations, and insufficient insulin secretion may be a potential cause of diabetic ketosis in MODY5.

Photocatalytic-induced bubble-propelled isotropic g-C3N4-coated carbon microsphere micromotors for dynamic removal of organic pollutants.

An isotropic bubble-propelled graphitic carbon nitride coated carbon microsphere (g-C3N4@CMS) micromotor that displays efficient self-propulsion powered by visible light irradiation and offers effective dynamic removal of organic pollutants for environmental applications is described. Its morphology, structure, and composition were systematically characterized, confirming the successful coating of g-C3N4 on the CMS surface and a core-shell structure. The photocatalytic-induced bubble propulsion of g-C3N4@CMS micromotors essentially stems from the asymmetrical photocatalytic redox reactions of g-C3N4 on the symmetrical surface of micromotors under visible light illumination. The stacking effect of g-C3N4 on the CMS surface results in a microporous structure that provides a highly reactive photocatalytic layer, which also leads to effective bubble evolution and propulsion at remarkable speeds of over 167.97 µm s-1 under 250 mW cm-2 visible light in the presence of 30% H2O2 fuel. The velocity can be easily and effectively adjusted by H2O2 fuel and the intensity of visible light. Furthermore, the motion state can be reversibly and wirelessly controlled by "switching on/off" light. Such coupling of the high photocatalytic activity of the porous g-C3N4 shell with the rapid movement of these light-driven micromotors, along with the corresponding fluid dynamics and mixing, result in greatly accelerated organic pollutant degradation. The adsorption kinetics have also been investigated and shown to follow pseudo-second-order kinetics. The strategy proposed here would inspire the designing of light-driven symmetrical micromotors because of the low cost, single component, and simple structure as well as facile and large-scale fabrication, which make them suitable for practical applications.

Many hands make light work: Evidence from China's anti-epidemic bonds.

Based on China's anti-epidemic bond data, this paper investigates stock market reactions to the anti-epidemic bond issuance announcements during the COVID-19 pandemic. We find that anti-epidemic bond issuance significantly increases the cumulative abnormal return (CAR) compared with conventional bond issuance.

Senecavirus A 2B protein suppresses type I interferon production by inducing the degradation of MAVS.

Senecavirus A (SVA) is an oncolytic virus, which can propagate in human tumor cells and has been used as an oncolytic virotherapy candidate in humans. Besides, SVA circulates in pigs and causes vesicles and coalescing erosions on the snouts and coronary bands in infected pigs and results in neonatal morbidity. SVA has evolved the ability to suppress host innate immune response to benefit viral replication. SVA 3Cpro and 2C protein inhibit the production of host type I interferon (IFN) by degradation of several components of innate immune pathway. In this study, for the first time, we determined that SVA 2B antagonized host innate immune response in both human and porcine cells. SVA 2B protein degraded mitochondrial antiviral-signaling protein (MAVS), a key host molecule in the innate immune pathway, and a colocalization and interaction between 2B and MAVS was observed in the context of viral infection. Further study showed that the 1-48 and 100-128 regions of 2B were essential for inhibition of type I IFN expression. In addition, we determined that 2B degraded MAVS depending on caspase-9 and caspase-3. In conclusion, our results revealed a novel strategy for SVA 2B protein to antagonize host innate immune response, which will help for clarification of the pathogenesis of SVA and provide an insight for oncolytic virotherapy of SVA.

A novel immune-related gene-based prognostic signature to predict biochemical recurrence in patients with prostate cancer after radical prostatectomy.

Accumulating evidences indicates that the immune landscape signature dramatically correlates with tumorigenesis and prognosis of prostate cancer (PCa). Here, we identified a novel immune-related gene-based prognostic signature (IRGPS) to predict biochemical recurrence (BCR) after radical prostatectomy. We also explored the correlation between IRGPS and tumor microenvironment. We identified an IRGPS consisting of seven immune-related genes (PPARGC1A, AKR1C2, COMP, EEF1A2, IRF5, NTM, and TPX2) that were related to the BCR-free survival of PCa patients. The high-risk patients exhibited a higher fraction of regulatory T cells and M2 macrophages than the low-risk BCR patients (P < 0.05) as well as a lower fraction of resting memory CD4 T cells and resting mast cells. These high-risk patients also had higher expression levels of CTLA4, TIGIT, PDCD1, LAG3, and TIM3. Finally, a strong correlation was detected between IRGPS and specific clinicopathological features, including Gleason scores and tumor stage. In conclusion, our study reveals the clinical significance and potential functions of the IRGPS, provides more data for predicting outcomes, and suggests more effective immunotherapeutic target strategies for PCa.

A window-space-directed assembly strategy for the construction of supertetrahedron-based zeolitic mesoporous metal-organic frameworks with ultramicroporous apertures for selective gas adsorption.

Despite their scarcity due to synthetic challenges, supertetrahedron-based metal-organic frameworks (MOFs) possess intriguing architectures, diverse functionalities, and superb properties that make them in-demand materials. Employing a new window-space-directed assembly strategy, a family of mesoporous zeolitic MOFs have been constructed herein from corner-shared supertetrahedra based on homometallic or heterometallic trimers [M3(OH/O)(COO)6] (M3 = Co3, Ni3 or Co2Ti). These MOFs consisted of close-packed truncated octahedral cages possessing a sodalite topology and large ß-cavity mesoporous cages (∼22 Å diameter) connected by ultramicroporous apertures (∼5.6 Å diameter). Notably, the supertetrahedron-based sodalite topology MOF combined with the Co2Ti trimer exhibited high thermal and chemical stability as well as the ability to efficiently separate acetylene (C2H2) from carbon dioxide (CO2).

Functional Assessment of Four Novel Immune-Related Biomarkers in the Pathogenesis of Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma whose pathogenesis is not well understood. We aimed at identifying novel immune-related biomarkers that could be valuable in the diagnosis and prognosis of ccRCC. METHODS: The Robust Rank Aggregation (RRA) method was used to integrate differently expressed genes (DEGs) of 7 Gene Expression Omnibus (GEO) datasets and obtain robust DEGs. Weighted gene co-expression network analyses (WGCNA) were performed to identify hub genes associated with clinical traits in The Cancer Genome Atlas (TCGA) database. Comprehensive bioinformatic analyses were used to explore the role of hub genes in ccRCC. RESULTS: Four hub genes IFI16, LMNB1, RHBDF2 and TACC3 were screened by the RRA method and WGCNA. These genes were found to be up-regulated in ccRCC, an upregulation that could be due to their associations with late TNM stages and tumor grades. The Receiver Operating Characteristic (ROC) curve and Kaplan-Meier survival analysis showed that the four hub genes had great diagnostic and prognostic values for ccRCC, while Gene Set Enrichment Analysis (GSEA) showed that they were involved in immune signaling pathways. They were also found to be closely associated with multiple tumor-infiltrating lymphocytes and critical immune checkpoint expressions. The results of Quantitative Real-time PCR (qRT-PCR) and immunohistochemical staining (IHC) analysis were consistent with bioinformatics analysis results. CONCLUSION: The four hub genes were shown to have great diagnostic and prognostic values and played key roles in the tumor microenvironment of ccRCC.

Spin curvature induced resistivity in epitaxial half-metallic CrO2 thin films.

Spin configuration inside a ferromagnetic metal influences its magnetoresistive behavior. The local spin curvature induces excess resistivity from the homogeneous ferromagnetic state. In this work, we characterize the spin curvature induced resistivity in epitaxial half-metallic CrO2 nanowires with 100% spin polarization. We control the magnitude of the spin curvature by introducing different geometric notches along the edge of the wire and applying an external magnetic field. Through magnetoresistance measurements and micromagnetic simulations, we uncover an empirical relationship between the spin curvature and the induced resistivity in this archetypal half-metallic solid. This relationship provides a quantitative method to calculate the resistance of magnetic domain walls or other spin textured states. We also study the influence of the thermal effect on the spin curvature induced resistivity across temperatures ranging from 10 K to 250 K. Thermal magnons worsen spin asymmetry considerably and suppress spin curvature induced resistivity at temperatures much lower than the ferromagnetic ordering temperature Tc.

A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder Cancer.

Background: TP53 gene mutation is one of the most common mutations in human bladder cancer (BC) and has been implicated in the progression and prognosis of BC. Methods: RNA sequencing data and TP53 mutation data in different populations and platforms were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database to determine and validate a TP53-associated immune prognostic signature (TIPS) based on differentially expressed immune-related genes (DEIGs) between muscle-invasive bladder cancer (MIBC) patients with and without TP53 mutations. Results: A total of 99 DEIGs were identified based on TP53 mutation status. TIPS including ORM1, PTHLH, and CTSE were developed and validated to identify high-risk prognostic group who had a poorer prognosis than low-risk prognostic group in TCGA and GEO database. The high-risk prognostic group were characterized by a higher abundance of regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages than the low-risk prognostic group. Moreover, they exhibited a lower abundance of CD56bright NK cells, higher expression of CTLA4, LAG3, PDCD1, TIGIT, and HAVCR2, as well as being more likely to respond to anti-PD-1, and neoadjuvant chemotherapy than the low-risk prognostic group. Based on TIPS and other clinical characteristics, a nomogram was constructed for clinical use. Conclusion: TIPS derived from TP53 mutation status is a potential prognostic signature or therapeutic target but additional prospective studies are necessary to confirm this potential.

Bubble-propelled micromotors based on hierarchical MnO2 wrapped carbon nanotube aggregates for dynamic removal of pollutants.

Water pollution is currently an urgent public health and environmental issue. Bubble-propelled micromotors might offer an effective approach for dealing with environmental contamination. Herein, we present the synthesis of multi-walled carbon nanotube (MWCNT)/manganese dioxide (MnO2) micromotors based on MWCNT aggregates as microscale templates by a simple one-step hydrothermal procedure. The morphology, composition, and structure of the obtained MWCNT/MnO2 micromotors were characterized in detail. The MnO2 nanoflakes formed a catalytic layer on the MWCNT backbone, which promoted effective bubble evolution and propulsion at remarkable speeds of 359.31 µm s-1. The bubble velocity could be modulated based on the loading of MnO2 nanoflakes. The rapid movement of these MWCNT/MnO2 catalytic micromotors resulted in a highly efficient moving adsorption platform, which considerably enhanced the effectiveness of water purification. Dynamic adsorption of organic dyes by the micromotors increased the degradation rate to approximately 4.8 times as high as that of their corresponding static counterparts. The adsorption isotherms and adsorption kinetics were also explored. The adsorption mechanism was well fitted by the Langmuir model, following pseudo-second-order kinetics. Thus, chemisorption of Congo red at the heterogeneous MnO2 wrapped microimotor surface was the rate determining step. The high propulsion speed and remarkable decontamination efficiency of the MWCNT/MnO2 micromotors indicate potential for environmental contamination applications.

Synthesis of one-dimensional calcium silicate nanowires as effective broadband optical limiters.

Synthesis of inorganic nanostructures with novel morphologies has attracted increasing attention from chemistry and materials science researchers. Calcium silicate nanowires (CaSiO3 NWs) were successfully prepared using a water-ethanol mixture solution system via hydrothermal synthesis. The resulting CaSiO3 NWs were uniform, with widths averaging 10-20 nm and lengths up to several micrometers. The synthesized silicate NWs were highly crystalline and mainly constituted of SiO4 tetrahedra. The nanosecond optical limiting (OL) effects were characterized using an open-aperture (OA) Z-scan technique with 4 ns laser pulses at 532 and 1064 nm. These CaSiO3 NWs exhibited excellent OL performance, superior to that of carbon nanotubes, which are a benchmark optical limiter. Input-fluence-dependent scattering measurements suggested that nonlinear scattering played an important role in the observed OL behavior in the CaSiO3 NWs at 532 and 1064 nm. This study provides new insights into the silicate nanowires, which will help in the design and preparation of 1D materials with improved nonlinear optical properties.

Deterministic Current Induced Magnetic Switching Without External Field using Giant Spin Hall Effect of ß-W.

Giant spin Hall effect (GSHE) has received significant attention for its potential in future spintronic applications. Spin current via GSHE-based thin films provides an effective and promising means to manipulate magnetization. However, an external in-plane magnetic field is required to consistently switch the perpendicular magnetic moment. We present an approach to realize field-free deterministic perpendicular magnetic switching with a new structure of FM/NM/FM. Our method takes advantage of the large spin Hall angle of transition metal ß-W, so that the critical switching current density is only on the order of 106A/cm2 in the absence of magnetic field.

Facile one-step fabrication of upconversion fluorescence carbon quantum dots anchored on graphene with enhanced nonlinear optical responses.

A novel nanocomposite hybrid, carbon quantum dots (CQD)/graphene oxide (GO), which combines the favorable optical properties of both its components, is synthesized by a facile one-step electrochemical method. Transmission electron microscopy, Raman spectroscopy, UV-vis spectroscopy, and fluorescence studies show that the CQDs uniformly attach on the GO surface, which enables highly efficient energy transfer between CQDs and GO. The nonlinear optical and optical limiting (OL) performances are investigated by the open-aperture Z-scan technique in the nanosecond regime using a laser with a wavelength of 532 nm. The as-prepared CQD/GO composite offers a significantly improved OL performance compared with GO because of the charge/energy transfer process between the CQDs and GO. The main contributors to the enhanced OL effect in the CQD/GO hybrid are a combination of nonlinear scattering and increased nonlinear absorption resulting from efficient charge/energy transfer at the CQD/GO interface.

Biomimetic composite scaffolds based on surface modification of polydopamine on electrospun poly(lactic acid)/cellulose nanofibrils.

An appropriate surface chemical property is crucial in tissue engineering scaffolds, which promotes cell attachment and proliferation. A biomimetic composite scaffold with a polydopamine (PDA) coating layer on electrospun poly(lactic acid) (PLA)/cellulose nanofibrils (CNF) composite nanofiber was developed in this study. PLA/CNF composite nanofibers were fabricated and then coated via treatment with a dopamine solution. The PDA coating layer was successfully formed on the surface of the PLA/CNF composite nanofiber by using a simple, environment-friendly, and effective procedure. Results indicated that the addition of CNF into the PLA matrix can effectively improve the deposition rate of the PDA coating layer on the surface of the composite nanofiber during the initial stage of coating because of hydrogen bonding between the CNF and PDA molecular chains. The hydrophilicity and mechanical properties of the PLA/CNF-PDA scaffold were higher than those of the PLA/CNF scaffold. In addition, the cell culture test showed that the adhesion, proliferation, and growth of human mesenchymal stem cells (hMSCs) cultured on the PLA/CNF-PDA scaffold were significantly enhanced relative to those cultured on the PLA/CNF scaffold because of the introduction of the PDA coating. This finding suggested that surface biofunctionalization via the PDA coating layer could simply and effectively enhance cell biocompatibility for polymer-based scaffolds.

Surface biofunctionalization of three-dimensional porous poly(lactic acid) scaffold using chitosan/OGP coating for bone tissue engineering.

As one of the stimulators on bone formation, osteogenic growth peptide (OGP) improves both proliferation and differentiation of the bone cells in vitro and in vivo. The aim of this work was the preparation of three dimensional porous poly(lactic acid) (PLA) scaffold with high porosity from PLA-dioxane-water ternary system with the use of vacuum-assisted solvent casting, phase separation, solvent extraction and particle leaching methods. Then, by surface coating of PLA scaffold with chitosan (CS)/OGP solution, biofunctionalization of PLA scaffold had been completed for application in bone regeneration. The effects of frozen temperature (-20, -50, -80°C) and PLA solution concentration (10, 12, 14wt%) on the microstructure, water absorption, porosity, hydrophilicity, mechanical properties, and biocompatibility of PLA and CS/OGP/PLA scaffold were investigated. Results showed that both PLA and CS/OGP/PLA scaffolds have an interconnected network structure and a porosity of up to 96.1% and 91.5%, respectively. The CS/OGP/PLA scaffold exhibited better hydrophilicity and mechanical properties than that of uncoated PLA scaffold. Moreover, the results of cell culture test showed that CS/OGP coating could stimulate the proliferation and growth of osteoblast cells on CS/OGP/PLA scaffold. These finding suggested that the surface biofunctionalization by CS/OGP coating layer could be an effective method on enhancing cell adhesion to synthetic polymer-based scaffolds in tissue engineering application and the developed porous CS/OGP/PLA scaffold should be considered as alternative biomaterials for bone regeneration.