Assessment of the competency of learner-centered teaching of clinical preceptor using the augmented Stanford Faculty Development Program Questionnaire (SFDPQ): a cross sectional comparative study.

BACKGROUND: Education is an important part of the work of most doctors. Clinical preceptors act as role models and supervisors. Preceptors' quality of supervision strongly influences the learning quality of clinical interns (Bartlett et al. BMC Med Educ 20:165, 2020). To ensure a consistent approach to every preceptorship experience, the competency of clinical preceptors should be assessed to ensure that the desired outcomes are achieved. This study aims to evaluate clinical preceptors' competency in learner-centered teaching, to provide constructive feedback to develop the preceptors' competency and improve supervisory skills and internship quality at Kunming Medical University (KMU) in Kunming of China. METHODS: This is a cross-sectional study with a quantitative self-administered online questionnaire. The convenience sampling technique was employed. In the undergraduate internship stage of KMU, clinical preceptors (N = 340) and interns (N = 487) were invited to use the augmented Stanford Faculty Development Program questionnaire (SFDPQ) (Stalmeijer et al. Med Teach 30:e272-e277, 2008), to (self-) assess the preceptor's competency of learner-centered teaching on a five-point scale (1 = strongly disagree, 5 = strongly agree). RESULTS: Two hundred twenty-eight preceptors and two hundred thirty-six interns completed the questionnaire correctly. Overall, the assessment was positive, but the preceptors' self-assessment significantly higher than the interns' (p < 0.00). The overall mean of each category of preceptors' self-assessment was greater than 4.5, with no difference based on educational qualification. Male preceptors scored significantly higher in two categories than female preceptors. Preceptors under 30 years of age with less than 5 years of teaching experience rated "Teacher's knowledge and attitude" lower than those over 40 years of age with more than 5 years of experience (p < 0.05). There were statistically significant differences in the four categories across disciplines (p < 0.05). Undergraduate interns rated "Teachers' knowledge" as the highest category and "Learning climate" as the lowest, and interns of different genders are evaluated without distinction in all categories of SFDPQ. CONCLUSIONS: Employing the augmented SFDPQ to evaluate learner-centered teaching competency of clinical preceptors, offers potentially useful information for delivering constructive feedback. Combining self-evaluations with learner evaluation data can contribute to exploring preceptor competency development framework to guide them in targeted learner-centered teaching skill and acquisition and improvement, finally improving the overall quality of internships.

Effects of TET2-mediated methylation reconstruction on A2058 melanoma cell sensitivity to matrix stiffness in a 3D culture system.

Matrix stiffness is a crucial factor in the tumor microenvironment, impacting tumor progression and development. TET2 is vital for epigenetic regulation in melanoma and is significantly reduced in advanced melanomas compared with nevi and thin melanomas. However, it is unclear how TET2 mediates the effect of matrix stiffness on melanoma cells. This study utilized A2058 cell lines and prepared different stiffness collagen hydrogels to evaluate TET2 overexpression (TET2OE) and mutant (TET2M) melanoma cells' activity, proliferation, and invasion. A2058 melanoma cells' viability and invasion decreased with increased matrix stiffness, with TET2OE cells experiencing a more significant impact than TET2M cells. Methylation analysis revealed that TET2 determines gene methylation levels, influencing cell-ECM interactions. Transcriptome analysis confirmed that TET2 promotes matrix stiffness's effect on melanoma cell fate. This research provides promising directions and opportunities for melanoma treatment.

3D bioprinting of an in vitro hepatoma microenvironment model: Establishment, evaluation, and anticancer drug testing.

Tumor behavior, including its response to treatments, is influenced by interactions between mesenchymal and malignant cells, as well as their spatial arrangement. To study tumor biology and evaluate anticancer drugs, accurate 3D tumor models are essential. Here, we developed an in vitro biomimetic hepatoma microenvironment model by combining an extracellular matrix (3DM-7721). Initially, the internal grid structure, composed of 10/6 % GelMA/gelatin loaded with SMMC-7721 cells, was printed using 3D bioprinting. The external component consisted of fibroblasts and human umbilical vein endothelial cells loaded with 10/3 % GelMA/gelatin. A control model (3DP-7721) lacked external cell loading. GelMA/gelatin hydrogels provided robust structural support and biocompatibility. The SMMC-7721 cells in the 3DM-7721 model exhibit superior tumor-associated gene expression and proliferation characteristics when compared to the 3DP-7721 model. Furthermore, the 3DM-7721 type exhibited increased resistance to anticancer agents. SMMC-7721 cells in the 3DM-7721 model exhibit significant tumorigenicity in nude mice. The 3DM-7721 model group showed pathological characteristics of malignant tumors, with a high degree of deterioration, and a significant positive correlation between malignant tumor-related gene pathways. This high-fidelity 3DM-7721 tumor microenvironment model is invaluable for studying tumor progression, devising effective treatment strategies, and discovering drugs. STATEMENT OF SIGNIFICANCE.

A multicrosslinked network composite hydrogel scaffold based on DLP photocuring printing for nasal cartilage repair.

Natural hydrogels are widely employed in tissue engineering and have excellent biodegradability and biocompatibility. Unfortunately, the utilization of such hydrogels in the field of three-dimensional (3D) printing nasal cartilage is constrained by their subpar mechanical characteristics. In this study, we provide a multicrosslinked network hybrid ink made of photocurable gelatin, hyaluronic acid, and acrylamide (AM). The ink may be processed into intricate 3D hydrogel structures with good biocompatibility and high stiffness properties using 3D printing technology based on digital light processing (DLP), including intricate shapes resembling noses. By varying the AM content, the mechanical behavior and biocompatibility of the hydrogels can be adjusted. In comparison to the gelatin methacryloyl (GelMA)/hyaluronic acid methacryloyl (HAMA) hydrogel, adding AM considerably enhances the hydrogel's mechanical properties while also enhancing printing quality. Meanwhile, the biocompatibility of the multicrosslinked network hydrogels and the development of cartilage were assessed using neonatal Sprague-Dawley (SD) rat chondrocytes (CChons). Cells sown on the hydrogels considerably multiplied after 7 days of culture and kept up the expression of particular proteins. Together, our findings point to GelMA/HAMA/polyacrylamide (PAM) hydrogel as a potential material for nasal cartilage restoration. The photocuring multicrosslinked network ink composed of appropriate proportions of GelMA/HAMA/PAM is very suitable for DLP 3D printing and will play an important role in the construction of nasal cartilage, ear cartilage, articular cartilage, and other tissues and organs in the future. Notably, previous studies have not explored the application of 3D-printed GelMA/HAMA/PAM hydrogels for nasal cartilage regeneration.

Effects of Staphylococcus aureus on stem cells and potential targeted treatment of inflammatory disorders.

Due to the advanced studies on stem cells in developmental biology, the roles of stem cells in the body and their phenotypes in related diseases have not been covered clearly. Meanwhile, with the intensive research on the mechanisms of stem cells in regulating various diseases, stem cell therapy is increasingly being attention because of its effectiveness and safety. As one of the most widely used stem cell in stem cell therapies, hematopoietic stem cell transplantation shows huge advantage in treatment of leukemia and other blood-malignant diseases. Besides, due to the effect of anti-inflammatory and immunomodulatory, mesenchymal stem cells could be a potential therapeutic strategy for variety infectious diseases. In this review, we summarized the effects of Staphylococcus aureus (S. aureus) and its components on different types of adult stem cells and their downstream signaling pathways. Also, we reviewed the roles of different kinds of stem cells in various disease models caused by S. aureus, providing new insights for applying stem cell therapy to treat infectious diseases.

Early megakaryocyte lineage-committed progenitors in adult mouse bone marrow.

Hematopoietic stem cells (HSCs) have been considered to progressively lose their self-renewal and differentiation potentials prior to the commitment to each blood lineage. However, recent studies have suggested that megakaryocyte progenitors (MkPs) are generated at the level of HSCs. In this study, we newly identified early megakaryocyte lineage-committed progenitors (MgPs) mainly in CD201-CD48- cells and CD48+ cells separated from the CD150+CD34-Kit+Sca-1+Lin- HSC population of the bone marrow in adult mice. Single-cell colony assay and single-cell transplantation showed that MgPs, unlike platelet-biased HSCs, had little repopulating potential in vivo, but formed larger megakaryocyte colonies in vitro (on average 8 megakaryocytes per colony) than did previously reported MkPs. Single-cell RNA sequencing supported that HSCs give rise to MkPs through MgPs along a Mk differentiation pathway. Single-cell reverse transcription polymerase chain reaction (RT-PCR) analysis showed that MgPs expressed Mk-related genes, but were transcriptionally heterogenous. Clonal culture of HSCs suggested that MgPs are not direct progeny of HSCs. We propose a differentiation model in which HSCs give rise to MgPs which then give rise to MkPs, supporting a classic model in which Mk-lineage commitment takes place at a late stage of differentiation.

Mapping Road Surface Type of Kenya Using OpenStreetMap and High-resolution Google Satellite Imagery.

Identifying road surface types (paved or unpaved) can ensure road vehicle safety, reduce energy consumption, and promote economic development. Existing studies identified road surface types by using sensors mounted on mobile devices and high-resolution satellite images that are not openly accessible, which makes it difficult to apply them to large-scale (e.g., national or regional) study areas. Addressing this issue, this study developed a dataset of road surface types (paved and unpaved) for the national road network of Kenya, containing 1,267,818 road segments classified as paved or unpaved. To accomplish this, this study proposes a method that integrates crowdsourced geographic data (OpenStreetMap) and Google satellite imagery to identify road surface types. The accuracy, recall, and F1 score of the method were all above 0.94, validating the effectiveness of the method. The data sources of the method are freely available, and the method may be applied to other countries and regions. The dataset developed based on the method can provide data support and decision support for local governments to improve road infrastructure.

3D Bioprinting-Based Dopamine-Coupled Flexible Material for Nasal Cartilage Repair.

INTRODUCTION: Since 3D printing can be used to design implants according to the specific conditions of patients, it has become an emerging technology in tissue engineering and regenerative medicine. How to improve the mechanical, elastic and adhesion properties of 3D-printed photocrosslinked hydrogels is the focus of cartilage tissue repair and reconstruction research. MATERIALS AND METHODS: We established a strategy for toughening hydrogels by mixing GelMA-DOPA (GD), which is prepared by coupling dopamine (DA) with GelMA, with HAMA, bacterial cellulose (BC) to produce composite hydrogels (HB-GD). HB-GD hydrogel scaffolds were characterized in vitro by scanning electron microscopy (SEM), Young's modulus, swelling property and rheological property tests. And biocompatibility and chondrogenic ability were tested by live/dead staining, DNA quantitative analysis and immunofluorescence staining. Combined with 3D bioprinting technology, mouse chondrocytes (ADTC5) were added to form a biological chain to construct an in vitro model, and the feasibility of the model for nasal cartilage regeneration was verified by cytology evaluation. RESULTS: With the increase of GD concentration, the toughness of the composite hydrogel increased (47.0 ± 2.7 kPa (HB-5GD)-158 ± 3.2 kPa (HB-20GD)), and it had excellent swelling properties, rheological properties and printing properties. The HB-GD composite hydrogel promoted the proliferation and differentiation of ATDC5. Cells in 3D printed scaffolds had higher survival rates (> 95%) and better protein expression than the encapsulated cultures. CONCLUSION: The HB-10GD hydrogel can be made into a porous scaffold with precise shape, good internal pore structure, high mechanical strength and good swelling rate through extrusion 3D printing. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Exploiting Nanotechnology for Drug Delivery: Advancing the Anti-Cancer Effects of Autophagy-Modulating Compounds in Traditional Chinese Medicine.

Background: Cancer continues to be a prominent issue in the field of medicine, as demonstrated by recent studies emphasizing the significant role of autophagy in the development of cancer. Traditional Chinese Medicine (TCM) provides a variety of anti-tumor agents capable of regulating autophagy. However, the clinical application of autophagy-modulating compounds derived from TCM is impeded by their restricted water solubility and bioavailability. To overcome this challenge, the utilization of nanotechnology has been suggested as a potential solution. Nonetheless, the current body of literature on nanoparticles delivering TCM-derived autophagy-modulating anti-tumor compounds for cancer treatment is limited, lacking comprehensive summaries and detailed descriptions. Methods: Up to November 2023, a comprehensive research study was conducted to gather relevant data using a variety of databases, including PubMed, ScienceDirect, Springer Link, Web of Science, and CNKI. The keywords utilized in this investigation included "autophagy", "nanoparticles", "traditional Chinese medicine" and "anticancer". Results: This review provides a comprehensive analysis of the potential of nanotechnology in overcoming delivery challenges and enhancing the anti-cancer properties of autophagy-modulating compounds in TCM. The evaluation is based on a synthesis of different classes of autophagy-modulating compounds in TCM, their mechanisms of action in cancer treatment, and their potential benefits as reported in various scholarly sources. The findings indicate that nanotechnology shows potential in enhancing the availability of autophagy-modulating agents in TCM, thereby opening up a plethora of potential therapeutic avenues. Conclusion: Nanotechnology has the potential to enhance the anti-tumor efficacy of autophagy-modulating compounds in traditional TCM, through regulation of autophagy.

Unraveling the immune landscape and therapeutic biomarker PMEPA1 for oxaliplatin resistance in colorectal cancer: A comprehensive approach.

Oxaliplatin (OXA) is a platinum-based chemotherapeutic agent with promising applications in the treatment of various malignancies, particularly colorectal cancer (CRC). However, the management of OXA resistance remains an ongoing obstacle in CRC therapy. This study aims to comprehensively investigate the immune landscape, targeted therapeutic biomarkers, and mechanisms that influence OXA resistance in CRC. Our results demonstrated that our OXA- resistant CRC prognostic model not only provides risk assessment for patients but also reflects the immune landscape of patients. Additionally, we identified prostate transmembrane protein, androgen-induced1 (PMEPA1) as a promising molecular targeted therapeutic biomarker for patients with OXA-resistant CRC. The mechanism of PMEPA1 may involve cell adhesion, pathways in cancer, and the TGF-ß signaling pathway. Furthermore, analysis of CRC clinical samples indicated that patients resistant to OXA exhibited elevated serum levels of TGF-ß1, increased expression of PMEPA1 in tumors, a lower proportion of CD8+ T cell positivity, and a higher proportion of M0 macrophage positivity, in comparison to OXA-sensitive individuals. Cellular experiments indicated that selective silencing of PMEPA1, alone or in combination with OXA, inhibited proliferation and metastasis in OXA-resistant CRC cells, HCT116R. Animal experiments further confirmed that PMEPA1 silencing suppressed subcutaneous graft tumor growth and liver metastasis in mice bearing HCT116R and synergistically enhanced the efficacy of OXA. These data highlight the potential of leveraging the therapeutic biomarker PMEPA1, CD8+ T cells, and M0 macrophages as innovative targets for effectively addressing the challenges associated with OXA resistance. Our findings hold promising implications for further clinical advancements in this field.

Hydrolytic endonucleolytic ribozyme (HYER) is programmable for sequence-specific DNA cleavage.

Ribozymes are catalytic RNAs with diverse functions including self-splicing and polymerization. This work aims to discover natural ribozymes that behave as hydrolytic and sequence-specific DNA endonucleases, which could be repurposed as DNA manipulation tools. Focused on bacterial group II-C introns, we found that many systems without intron-encoded protein propagate multiple copies in their resident genomes. These introns, named HYdrolytic Endonucleolytic Ribozymes (HYERs), cleaved RNA, single-stranded DNA, bubbled double-stranded DNA (dsDNA), and plasmids in vitro. HYER1 generated dsDNA breaks in the mammalian genome. Cryo-electron microscopy analysis revealed a homodimer structure for HYER1, where each monomer contains a Mg2+-dependent hydrolysis pocket and captures DNA complementary to the target recognition site (TRS). Rational designs including TRS extension, recruiting sequence insertion, and heterodimerization yielded engineered HYERs showing improved specificity and flexibility for DNA manipulation.

A heparin-functionalized bioink with sustained delivery of vascular endothelial growth factor for 3D bioprinting of prevascularized dermal constructs.

Skin tissue engineering faces challenges due to the absence of vascular architecture, impeding the development of permanent skin replacements. To address this, a heparin-functionalized 3D-printed bioink (GH/HepMA) was formulated to enable sustained delivery of vascular endothelial growth factor (VEGF), comprising 0.3 % (w/v) hyaluronic acid (HA), 10 % (w/v) gelatin methacrylate (GelMA), and 0.5 % (w/v) heparin methacrylate (HepMA). The bioink was then used to print dermal constructs with angiogenic functions, including fibroblast networks and human umbilical vein endothelial cell (HUVEC) networks. GH/HepMA, with its covalently cross-linked structure, exhibits enhanced mechanical properties and heparin stability, allowing for a 21-day sustained delivery of VEGF. Cytocompatibility experiments showed that the GH/HepMA bioink supported fibroblast proliferation and promoted collagen I production. With VEGF present, the GH/HepMA bioink promoted HUVEC proliferation, migration, as well as the formation of a richer capillary-like network. Furthermore, HA within the GH/HepMA bioink enhanced rheological properties and printability. Additionally, 3D-bioprinted dermal constructs showed significant deposition of collagen I and III and mature stable capillary-like structures along the axial direction. In summary, this study offers a promising approach for constructing biomimetic multicellular skin substitutes with angiogenesis-induced functions.

Dipole-Dipole Tuned Electronic Reconfiguration of Defective Carbon Sites for Efficient Oxygen Reduction into H2O2.

Metal-free carbon-based materials are one of the most promising electrocatalysts toward 2-electron oxygen reduction reaction (2e-ORR) for on-site production of hydrogen peroxide (H2O2), which however suffer from uncontrollable carbonizations and inferior 2e-ORR selectivity. To this end, a polydopamine (PDA)-modified carbon catalyst with a dipole-dipole enhancement is developed via a calcination-free method. The H2O2 yield rate outstandingly reaches 1.8 mol gcat -1 h-1 with high faradaic efficiency of above 95% under a wide potential range of 0.4-0.7 VRHE, overwhelming most of carbon electrocatalysts. Meanwhile, within a lab-made flow cell, the synthesized ORR electrode features an exceptional stability for over 250 h, achieved a pure H2O2 production efficacy of 306 g kWh-1. By virtue of its industrial-level capabilities, the established flow cell manages to perform a rapid pulp bleaching within 30 min. The superior performance and enhanced selectivity of 2e-ORR is experimentally revealed and attributed to the electronic reconfiguration on defective carbon sites induced by non-covalent dipole-dipole influence between PDA and carbon, thereby prohibiting the cleavage of O-O in OOH intermediates. This proposed strategy of dipole-dipole effects is universally applicable over 1D carbon nanotubes and 2D graphene, providing a practical route to design 2e-ORR catalysts.

The effect of Staphylococcus aureus on innate and adaptive immunity and potential immunotherapy for S. aureus-induced osteomyelitis.

Osteomyelitis is a chronic inflammatory bone disease caused by infection of open fractures or post-operative implants. Particularly in patients with open fractures, the risk of osteomyelitis is greatly increased as the soft tissue damage and bacterial infection are often more severe. Staphylococcus aureus, one of the most common pathogens of osteomyelitis, disrupts the immune response through multiple mechanisms, such as biofilm formation, virulence factor secretion, and metabolic pattern alteration, which attenuates the effectiveness of antibiotics and surgical debridement toward osteomyelitis. In osteomyelitis, immune cells such as neutrophils, macrophages and T cells are activated in response to pathogenic bacteria invasion with excessive inflammatory factor secretion, immune checkpoint overexpression, and downregulation of immune pathway transcription factors, which enhances osteoclastogenesis and results in bone destruction. Therefore, the study of the mechanisms of abnormal immunity will be a new breakthrough in the treatment of osteomyelitis.

Apolipoprotein E deficiency potentiates macrophage against Staphylococcus aureus in mice with osteomyelitis via regulating cholesterol metabolism.

Introduction: Staphylococcus aureus (S. aureus) osteomyelitis causes a variety of metabolism disorders in microenvironment and cells. Defining the changes in cholesterol metabolism and identifying key factors involved in cholesterol metabolism disorders during S. aureus osteomyelitis is crucial to understanding the mechanisms of S. aureus osteomyelitis and is important in designing host-directed therapeutic strategies. Methods: In this study, we conducted in vitro and in vivo experiments to define the effects of S. aureus osteomyelitis on cholesterol metabolism, as well as the role of Apolipoprotein E (ApoE) in regulating cholesterol metabolism by macrophages during S. aureus osteomyelitis. Results: The data from GSE166522 showed that cholesterol metabolism disorder was induced by S. aureus osteomyelitis. Loss of cholesterol from macrophage obtained from mice with S. aureus osteomyelitis was detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS), which is consistent with Filipin III staining results. Changes in intracellular cholesterol content influenced bactericidal capacity of macrophage. Subsequently, it was proven by gene set enrichment analysis and qPCR, that ApoE played a key role in developing cholesterol metabolism disorder in S. aureus osteomyelitis. ApoE deficiency in macrophages resulted in increased resistance to S. aureus. ApoE-deficient mice manifested abated bone destruction and decreased bacteria load. Moreover, the combination of transcriptional analysis, qPCR, and killing assay showed that ApoE deficiency led to enhanced cholesterol biosynthesis in macrophage, ameliorating anti-infection ability. Conclusion: We identified a previously unrecognized role of ApoE in S. aureus osteomyelitis from the perspective of metabolic reprogramming. Hence, during treating S. aureus osteomyelitis, considering cholesterol metabolism as a potential therapeutic target presents a new research direction.

Effects of Dopamine on stem cells and its potential roles in the treatment of inflammatory disorders: a narrative review.

Inflammation is the host's protective response against harmful external stimulation that helps tissue repair and remodeling. However, excessive inflammation seriously threatens the patient's life. Due to anti-inflammatory effects, corticosteroids, immunosuppressants, and monoclonal antibodies are used to treat various inflammatory diseases, but drug resistance, non-responsiveness, and severe side effect limit their development and application. Therefore, developing other alternative therapies has become essential in anti-inflammatory therapy. In recent years, the in-depth study of stem cells has made them a promising alternative drug for the treatment of inflammatory diseases, and the function of stem cells is regulated by a variety of signals, of which dopamine signaling is one of the main influencing factors. In this review, we review the effects of dopamine on various adult stem cells (neural stem cells, mesenchymal stromal cells, hematopoietic stem cells, and cancer stem cells) and their signaling pathways, as well as the application of some critical dopamine receptor agonists/antagonists. Besides, we also review the role of various adult stem cells in inflammatory diseases and discuss the potential anti-inflammation function of dopamine receptors, which provides a new therapeutic target for regenerative medicine in inflammatory diseases.

Constructing epidermal rete ridges using a composite hydrogel to enhance multiple signaling pathways for the maintenance of epidermal stem cell niche.

The undulating microstructure rete ridge (RR) located at the junction between the dermis and epidermis plays a crucial role in improving skin mechanical properties and maintaining skin homeostasis. However, the investigation of RR microstructures is usually neglected in current tissue engineering for skin regeneration. Here, to create an epidermal model with RR microstructures, keratinocytes were cultured on a patterned GelMA-PEGDA hydrogel constructed using molding technology. Furthermore, grafting acryloylated Arg-Gly-Asp (RGD) peptides on the hydrogel surface significantly improved cell adhesion, fusion, and development. RT-PCR, Western blot, and immunofluorescence staining confirmed that cells on RR microstructures exhibited higher gene and protein expression associated with epidermal stem cells. RNA sequencing analysis of cells on RR microstructure showed higher gene expression profiles related to stem cell maintenance, basement membrane formation, and epidermal development. Furthermore, RT-PCR analysis of epidermal models of various dimensions demonstrated that smaller microstructures were more conducive to epidermal stem cell marker gene expression, which is analogous to human skin. Overall, we have successfully developed a method for integrating RR microstructures into an epidermal model that mimics natural skin to maintain epidermal stem cell niche, providing a valuable reference for researching skin regeneration within the fields of tissue engineering and regenerative medicine. STATEMENT OF SIGNIFICANCE: This study presents a method for precisely fabricating microstructures of skin rete ridges using composite hydrogels, thereby creating a skin model that mimics natural human skin. The findings reveal that this microstructure provides a stem cell niche that regulates the pathways and promotes the expression of proteins related to epidermal stem cells. This work advances the functional properties of tissue engineered skin and holds promise for improving the therapeutic efficacy of artificial skin grafts for the skin wounds.

Predicting the Prognosis of Multiple System Atrophy Using Cluster and Principal Component Analysis.

BACKGROUND: Multiple system atrophy (MSA) is an intractable neurodegenerative disorder with poorly understanding of prognostic factors. OBJECTIVE: The purpose of this retrospective longitudinal study was to explore the main predictors of survival of MSA patients with new clinical subtypes based on cluster analysis. METHODS: A total of 153 Chinese MSA patients were recruited in our study. The basic demographic data and motor and nonmotor symptoms were assessed. Cluster and principal component analysis (PCA) were used to eliminate collinearity and search for new clinical subtypes. The multivariable Cox regression was used to find factors associated with survival in MSA patients. RESULTS: The median survival time from symptom onset to death (estimated using data from all patients by Kaplan-Meier analysis) was 6.3 (95% CI = 6.1-6.7) years. The survival model showed that a shorter survival time was associated with motor principal component (PC)1 (HR = 1.71, 95% CI: 1.26-2.30, p < 0.001) and nonmotor PC3 (HR = 1.68, 95% CI: 1.31-2.10, p < 0.001) through PCA. Four clusters were identified: Cluster 1 (mild), Cluster 2 (mood disorder-dominant), Cluster 3 (axial symptoms and cognitive impairment-dominant), and Cluster 4 (autonomic failure-dominant). Multivariate Cox regression indicated that Cluster 3 (HR = 4.15, 95% CI: 1.73-9.90, p = 0.001) and Cluster 4 (HR = 4.18, 95% CI: 1.73-10.1, p = 0.002) were independently associated with shorter survival time. CONCLUSION: More serious motor symptoms, axial symptoms such as falls and dysphagia, orthostatic hypotension, and cognitive impairment were associated with poor survival in MSA via PCA and cluster analysis.

Curcumin Attenuates Periodontal Injury via Inhibiting Ferroptosis of Ligature-Induced Periodontitis in Mice.

Periodontitis is a chronic infectious disease characterized by the destruction of connective tissue and alveolar bone that eventually leads to tooth loss. Ferroptosis is an iron-dependent regulated cell death and is involved in ligature-induced periodontitis in vivo. Studies have demonstrated that curcumin has a potential therapeutic effect on periodontitis, but the mechanism is still unclear. The purpose of this study was to investigate the protective effects of curcumin on alleviating ferroptosis in periodontitis. Ligature-induced periodontal-diseased mice were used to detect the protective effect of curcumin. The level of superoxide dismutase (SOD), malondialdehyde (MDA) and total glutathione (GSH) in gingiva and alveolar bone were assayed. Furthermore, the mRNA expression levels of acsl4, slc7a11, gpx4 and tfr1 were measured using qPCR and the protein expression of ACSL4, SLC7A11, GPX4 and TfR1 were investigated by Western blot and immunocytochemistry (IHC). Curcumin reduced the level of MDA and increased the level of GSH. Additionally, curcumin was proven to significantly increase the expression levels of SLC7A11 and GPX4 and inhibit the expression of ACSL4 and TfR1. In conclusion, curcumin plays a protective role by inhibiting ferroptosis in ligature-induced periodontal-diseased mice.

3D printing to construct in vitro multicellular models of melanoma.

Currently, there is a lack of suitable models for in-vitro studies of malignant melanoma and traditional single cell culture models no longer reproduce tumor structure and physiological complexity well. The tumor microenvironment is closely related to carcinogenesis and it is particularly important to understand how tumor cells interact and communicate with surrounding nonmalignant cells. Three-dimensional (3D) in vitro multicellular culture models can better simulate the tumor microenvironment due to their excellent physicochemical properties. In this study, 3D composite hydrogel scaffolds were prepared from gelatin methacrylate and polyethylene glycol diacrylate hydrogels by 3D printing and light curing techniques, and 3D multicellular in vitro tumor culture models were established by inoculating human melanoma cells (A375) and human fibroblasts cells on them. The cell proliferation, migration, invasion, and drug resistance of the 3D multicellular in vitro model was evaluated. Compared with the single-cell model, the cells in the multicellular model had higher proliferation activity and migration ability, and were easy to form dense structures. Several tumor cell markers, such as matrix metalloproteinase-9 (MMP-9), MMP-2, and vascular endothelial growth factor, were highly expressed in the multicellular culture model, which were more favorable for tumor development. In addition, higher cell survival rate was observed after exposure to luteolin. The anticancer drug resistance result of the malignant melanoma cells in the 3D bioprinted construct demonstrated physiological properties, suggesting the promising potential of current 3D printed tumor model in the development of personalized therapy, especially for discovery of more conducive targeted drugs.