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1.
Cancer Cell Int ; 24(1): 267, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39068458

ABSTRACT

BACKGROUND: To explore the impact of ARGs on the prognosis of NSCLC, and its correlation with clinicopathological parameters and immune microenvironment. Preliminary research on the biological functions of CEBPA in NSCLC. METHODS: Using consensus clustering analysis to identify molecular subtypes of ARGs in NSCLC patients; employing LASSO regression and multivariate Cox analysis to select 7 prognostic risk genes and construct a prognostic risk model; validating independent prognostic factors of NSCLC using forest plot analysis; analyzing immune microenvironment correlations using ESTIMATE and ssGSEA; assessing correlations between prognostic risk genes via qPCR and Western blot in NSCLC; measuring mRNA and protein expression levels of knocked down and overexpressed CEBPA in NSCLC using CCK-8 and EdU assays; evaluating the effects of knocked down and overexpressed CEBPA on cell proliferation using Transwell experiments; examining the correlation of CEBPA with T cells and B cells using mIHC analysis. RESULTS: Consensus clustering analysis identified three molecular subtypes, suggesting significant differential expression of these ARGs in NSCLC prognosis and clinical pathological parameters. There was significant differential expression between the two risk groups in the prognostic risk model, with P < 0.001. The risk score of the prognostic risk model was also P < 0.001. CEBPA exhibited higher mRNA and protein expression levels in NSCLC cell lines. Knockdown of CEBPA significantly reduced mRNA and protein expression levels of CEBPB, YWHAZ, ABL1, and CDK1 in H1650 and A549 cells. siRNA-mediated knockdown of CEBPA markedly inhibited proliferation, migration, and invasion of NSCLC cells, whereas overexpression of CEBPA showed the opposite trend. mIHC results indicated a significant increase in CD3 + CD4+, CD3 + CD8+, and CD20 + cell counts in the high CEBPA expression group. CONCLUSIONS: The risk score of the prognostic risk model can serve as an independent prognostic factor, guiding the diagnosis and treatment of NSCLC. CEBPA may serve as a potential tumor biomarker and immune target, facilitating further exploration of the biological functions and immunological relevance in NSCLC.

2.
Nanoscale ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39011749

ABSTRACT

With the ongoing trend of seeking miniaturization and enhanced performance for electronic devices, effective thermal management has emerged as a critical concern. The discovery and investigation of high thermal conductivity (κ) materials have proved to be pivotal in addressing this challenge. This study aims to explore the distinctive properties and potential applications of nitrogen substituted diamane (NCCN), a two-dimensional material with a diamond-like structure composed of carbon and nitrogen atoms. This work systematically delves into NCCN's thermal, mechanical, and electrical properties. It is predicted that NCCN exhibits an exceptional κ, ∼2288 W m-1 K-1, at room temperature (300 K) by combining the machine-learning interatomic potential method and the phonon Boltzmann transport equation, surpassing that of H-diamane and rivaling that of diamond, and an impressive electronic band gap of ∼4.47 eV (PBE). For mechanical properties, the stress-strain relationship reveals that NCCN exhibits isotropic elastic properties and anisotropic tensile strengths. Additionally, the variations in NCCN's κ and electronic energy band structure under different strains underscore its substantial potential in the field of thermoelectric applications.

3.
Small ; : e2403490, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39031997

ABSTRACT

The miniaturization, integration, and increased power of electronic devices have exacerbated serious heat dissipation issues. Thermally conductive adhesives, which effectively transfer heat and firmly bond components, are critical for addressing these challenges. This paper innovatively proposed a composite comprising inorganic phosphate/alumina as a matrix and diamond as filler. The composite achieved an isotropic thermal conductivity (TC) of up to 18.96 W m-1 K-1, significantly surpassing existing reports while maintaining electrical insulation. First-principles calculations and experimental tests confirmed that the high TC of phosphate and excellent interface contact ensured efficient heat transfer. To optimize bonding performance, a modified-diamond/Al(H2PO4)3@epoxy hybrid composite is subsequently developed using an organic modification method. The unique hybrid structure, combining inorganic thermal pathways and an organic adhesive network, enabled the hybrid composite to simultaneously possess a high TC (3.23 W m-1 K-1) and strong adhesion (14.35 MPa). Compared to previous reports, the comprehensive performance of this hybrid thermally conductive adhesive is exceptionally remarkable. The superior heat dissipation capability of the hybrid thermal adhesive is demonstrated in chip cooling scenarios. This organic/inorganic hybrid approach offered a new direction for obtaining advanced thermal interface materials, demonstrating significant application potential in chip soldering, packaging, and heat dissipation.

4.
J Am Chem Soc ; 146(29): 20270-20278, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39011628

ABSTRACT

We introduce a method for the (Z)-selective aminoallylation of a range of ketones to prepare allylic 1,2-amino tertiary alcohols with excellent diastereo- and enantioselectivity. Copper-catalyzed reductive couplings of 2-azatrienes with aryl/alkyl and dialkyl ketones proceed with Ph-BPE as the supporting ligand, generating anti-amino alcohols with >98% (Z)-selectivity under mild conditions. The utility of the products is highlighted through several transformations, including those that leverage the (Z)-allylic amine moiety for diastereoselective reactions of the alkene. Calculations illustrate Curtin-Hammett control in the product formation over other possible isomers and the origin of (Z)-selectivity.

5.
Opt Express ; 32(11): 19467-19479, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38859081

ABSTRACT

Computational micro-spectrometers comprised of detector arrays and encoding structure arrays, such as on-chip Fabry-Perot (FP) cavity filters, have great potential in many in-situ applications owing to their compact size and snapshot imaging ability. Given manufacturing deviation and environmental influence are inevitable, easy and effective calibration for spectrometer is necessary, especially for in-situ applications. Currently calibration strategies based on iterative algorithms or neural networks require accurate measurements of pixel-level (spectral) encoding functions through monochromator or large amounts of standard samples. These procedures are time-consuming and expensive, thereby impeding in-situ applications. Meta-learning algorithms with few-shot learning ability can address this challenge by incorporating the prior knowledge in the simulated dataset. In this work, we propose a meta-learning algorithm free of measuring encoding function or large amounts of standard samples to calibrate a micro-spectrometer with manufacturing deviation effectively. Our micro-spectrometer comprises 16 types of FP filters covering a wavelength range of 550-720 nm. The center wavelength of each filter type deviates from the design up to 6 nm. After calibration with 15 different color data, the average reconstruction error on the test dataset decreased from 7.2 × 10-3 to 1.2 × 10-3, and further decreased to 9.4 × 10-4 when the calibration data increased to 24. The performance is comparable to algorithms trained with measured encoding function both in reconstruction error and generalization ability. We estimated that the cost of in-situ calibration through reflectance measurements of color chart decreased to one percent of the cost through monochromator measurements. By exploiting prior deviation information in simulation data with meta-learning, the efficiency and cost of calibration are significantly improved, thereby facilitating the large-scale production and in-situ application of micro-spectrometers.

6.
J Neurosurg Spine ; : 1-9, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38848601

ABSTRACT

OBJECTIVE: There are limited data about the influence of the lumbar paraspinal muscles on the maintenance of sagittal alignment after pedicle subtraction osteotomy (PSO) and the risk factors for sagittal realignment failure. The authors aimed to investigate the influence of preoperative lumbar paraspinal muscle quality on the postoperative maintenance of sagittal alignment after lumbar PSO. METHODS: Patients who underwent lumbar PSO with preoperative lumbar MRI and pre- and postoperative whole-spine radiography in the standing position were included. Spinopelvic measurements included pelvic incidence, sacral slope, pelvic tilt, L1-S1 lordosis, T4-12 thoracic kyphosis, spinosacral angle, C7-S1 sagittal vertical axis (SVA), T1 pelvic angle, and mismatch between pelvic incidence and L1-S1 lordosis. Validated custom software was used to calculate the percent fat infiltration (FI) of the psoas major, as well as the erector spinae and multifidus (MF). A multivariable linear mixed model was applied to further examine the association between MF FI and the postoperative progression of SVA over time, accounting for repeated measures over time that were adjusted for age, sex, BMI, and length of follow-up. RESULTS: Seventy-seven patients were recruited. The authors' results demonstrated significant correlations between MF FI and the maintenance of corrected sagittal alignment after PSO. After adjustment for the aforementioned parameters, the model showed that the MF FI was significantly associated with the postoperative progression of positive SVA over time. A 1% increase from the preoperatively assessed total MF FI was correlated with an increase of 0.92 mm in SVA postoperatively (95% CI 0.42-1.41, p < 0.0001). CONCLUSIONS: This study included a large patient cohort with midterm follow-up after PSO and emphasized the importance of the lumbar paraspinal muscles in the maintenance of sagittal alignment correction. Surgeons should assess the quality of the MF preoperatively in patients undergoing PSO to identify patients with severe FI, as they may be at higher risk for sagittal decompensation.

7.
J Neurosurg Spine ; : 1-9, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38875728

ABSTRACT

OBJECTIVE: The paraspinal muscles play an essential role in the stabilization of the lumbar spine. Lumbar paraspinal muscle atrophy has been linked to chronic back pain and degenerative processes within the spinal motion segment. However, the relationship between the different paraspinal muscle groups and facet joint osteoarthritis (FJOA) has not been fully explored. METHODS: In this cross-sectional study, the authors analyzed adult patients who underwent lumbar spinal surgery between December 2014 and March 2023 for degenerative spinal conditions and had preoperative MRI and CT scans. The fatty infiltration (FI) and functional cross-sectional area (fCSA) of the psoas, erector spinae, and multifidus muscles were assessed on axial T2-weighted MR images at the level of the upper endplate of L4 based on established studies and calculated using custom-made software. Intervertebral disc degeneration at each lumbar level was evaluated using the Pfirrmann grading system. The grades from each level were summed to report the cumulative lumbar Pfirrmann grade. Weishaupt classification (0-3) was used to assess FJOA at all lumbar levels (L1 to S1) on preoperative CT scans. The total lumbar FJOA score was determined by adding the Weishaupt grades of both sides at all 5 levels. Correlation and linear regression analyses were conducted to assess the relationship between FJOA and paraspinal muscle parameters. RESULTS: A total of 225 patients (49.7% female) with a median age of 61 (IQR 54-70) years and a median BMI of 28.3 (IQR 25.1-33.1) kg/m2 were included. After adjustment for age, sex, BMI, and the cumulative lumbar Pfirrmann grade, only multifidus muscle fCSA (estimate -4.69, 95% CI -6.91 to -2.46; p < 0.001) and FI (estimate 0.64, 95% CI 0.33-0.94; p < 0.001) were independently predicted by the total FJOA score. A similar relation was seen with individual Weishaupt grades of each lumbar level after controlling for age, sex, BMI, and the Pfirrmann grade of the corresponding level. CONCLUSIONS: Atrophy of the multifidus muscle is significantly associated with FJOA in the lumbar spine. The absence of such correlation for the erector spinae and psoas muscles highlights the unique link between multifidus muscle quality and the degeneration of the spinal motion segment. Further research is necessary to establish the causal link and the clinical implications of these findings.

8.
Nat Commun ; 15(1): 5197, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890294

ABSTRACT

Untethered miniature soft robots have significant application potentials in biomedical and industrial fields due to their space accessibility and safe human interaction. However, the lack of selective and forceful actuation is still challenging in revolutionizing and unleashing their versatility. Here, we propose a focused ultrasound-controlled phase transition strategy for achieving millimeter-level spatially selective actuation and Newton-level force of soft robots, which harnesses ultrasound-induced heating to trigger the phase transition inside the robot, enabling powerful actuation through inflation. The millimeter-level spatial resolution empowers single robot to perform multiple tasks according to specific requirements. As a concept-of-demonstration, we designed soft robot for liquid cargo delivery and biopsy robot for tissue acquisition and patching. Additionally, an autonomous control system is integrated with ultrasound imaging to enable automatic acoustic field alignment and control. The proposed method advances the spatiotemporal response capability of untethered miniature soft robots, holding promise for broadening their versatility and adaptability.


Subject(s)
Robotics , Robotics/instrumentation , Robotics/methods , Equipment Design , Humans , Ultrasonic Waves , Phase Transition , Ultrasonography/methods , Ultrasonography/instrumentation
9.
Food Chem ; 457: 140077, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38905833

ABSTRACT

Human intestinal microbiota plays a crucial role in converting secoisolariciresinol diglucoside, a lignan found in flaxseed, to enterodiol, which has a range of health benefits: antioxidative, antitumor, and estrogenic/anti-estrogenic effects. Given the high secoisolariciresinol diglucoside content in flaxseed cake, this study investigated the potential of co-fermenting flaxseed cake with fermented soybean product to isolate bacterial strains that effectively convert secoisolariciresinol diglucoside to enterodiol in a controlled environment (in vitro). The co-fermentation process with stinky tofu microbiota significantly altered the lignan, generating 12 intermediate lignan metabolites as identified by targeted metabolomics. One particular promising strain, ZB26, demonstrated an impressive ability to convert secoisolariciresinol diglucoside. It achieved a conversion rate of 87.42 ± 0.33%, with secoisolariciresinol and enterodiol generation rates of 94.22 ± 0.51% and 2.91 ± 0.03%, respectively. Further optimization revealed, under specific conditions (0.5 mM secoisolariciresinol diglucoside, pH 8, 30 °C for 3 days), ZB26 could convert an even higher percentage (97.75 ± 0.05%) of the secoisolariciresinol diglucoside to generate secoisolariciresinol (103.02 ± 0.16%) and enterodiol (3.18 ± 0.31%). These findings suggest that the identified strains ZB26 have promising potential for developing functional foods and ingredients enriched with lignans.

10.
Eur Spine J ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937347

ABSTRACT

PURPOSE: The literature is scarce in exploring the role of imaging parameters like ultrasound (US) as a biomarker for surgical outcomes. The purpose of this study is to investigate the associations between skin US parameters and revision surgery following spine lumbar fusion. METHODS: Posterior lumbar fusion patients with 2-years follow-up were assessed. Previous fusion or revision not due to adjacent segment disease (ASD) were excluded. Revisions were classified as cases and non-revision were classified as controls. US measurements conducted at two standardized locations on the lumbar back. Skin echogenicity of the average dermal (AD), upper 1/3 of the dermal (UD), lower 1/3 of the dermal (LD), and subcutaneous layer were measured. Echogenicity was calculated with the embedded echogenicity function of our institution's imaging platform (PACS). Statistical significance was set at p < 0.05. RESULTS: A total of 128 patients (51% female, age 62 [54-72] years) were included in the final analysis. 17 patients required revision surgery. AD, UD, and LD echogenicity showed significantly higher results among revision cases 124.5 [IQR = 115.75,131.63], 128.5 [IQR = 125,131.63] and 125.5 [IQR = 107.91,136.50] compared to the control group 114.3 [IQR = 98.83,124.8], 118.5 [IQR = 109.28,127.50], 114 [IQR = 94.20,126.75] respectively. CONCLUSION: The findings of this study demonstrate a significant association between higher echogenicity values in different layers of the dermis and requiring revision surgery. The results provide insights into the potential use of skin US parameters as predictors for revision surgery. These findings may reflect underlying alterations in collagen. Further research is warranted to elucidate the mechanisms driving these associations.

11.
Adv Mater ; : e2404369, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38938165

ABSTRACT

By incorporating soft materials into the architecture, flexible mechanical metamaterials enable promising applications, e.g., energy modulation, and shape morphing, with a well-controllable mechanical response, but suffer from spatial and temporal programmability towards higher-level mechanical intelligence. One feasible solution is to introduce snapping structures and then tune their responses by accurately tailoring the stress-strain curves. However, owing to the strongly coupled nonlinearity of structural deformation and material constitutive model, it is difficult to deduce their stress-strain curves using conventional ways. Here, a machine learning pipeline is trained with the finite element analysis data that considers those strongly coupled nonlinearities to accurately tailor the stress-strain curves of snapping metamaterialfor on-demand mechanical response with an accuracy of 97.41%, conforming well to experiment. Utilizing the established approach, the energy absorption efficiency of the snapping-metamaterial-based device can be tuned within the accessible range to realize different rebound heights of a falling ball, and soft actuators can be spatially and temporally programmed to achieve synchronous and sequential actuation with a single energy input. Purely relying on structure designs, the accurately tailored metamaterials increase the devices' tunability/programmability. Such an approach can potentially extend to similar nonlinear scenarios towards predictable or intelligent mechanical responses.

12.
Nanoscale ; 16(25): 12149-12162, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38833269

ABSTRACT

Together, tumor and virus-specific tissue-resident CD8+ memory T cells (TRMs) of hepatocellular carcinoma (HCC) patients with Hepatitis B virus (HBV) infection can provide rapid frontline immune surveillance. The quantity and activity of CD8+ TRMs were correlated with the relapse-free survival of patients with improved health. However, HBV-specific CD8+ TRMs have a more exhausted phenotype and respond more actively under anti-PDL1 or PD1 treatment of HBV+HCC patients. Vaccination strategies that induce a strong and sustained CD8+ TRMs response are quite promising. Herein, a biodegradable poly(D,L-lactide-co-glycolide) microsphere and nanosphere particle (PLGA N.M.P) delivery system co-assembled by anti-PD1 antibodies (aPD1) and loaded with ovalbumin (OVA-aPD1 N.M.P) was fabricated and characterized for size (200 nm and 1 µm diameter), charge (-15 mV), and loading efficiencies of OVA (238 µg mg-1 particles) and aPD1 (40 µg mg-1 particles). OVA-aPD1 N.M.P could stimulate the maturation of BMDCs and enhance the antigen uptake and presentation by 2-fold compared to free OVA. The nanoparticles also induced the activation of macrophages (RAW 264.7) to produce a high level of cytokines, including TNF-α, IL-6 and IL-10. In vivo stimulation of mice using OVA-aPD1 N.M.P robustly enhanced IFN-γ-producing-CD8+ T cell infiltration in tumor tissues and the secretion of IgG and IgG2a/IgG1 antibodies. OVA-aPD1 N.M.P delivered OVA to increase the activation and proliferation of OVA-specific CD8+ TRMs, and its combination with anti-PD1 antibodies promoted complete tumor rejection by the reversal of tumor-infiltrating CD8+ T cell exhaustion. Thus, PLGA N.M.P could induce a strong CD8+ TRMs response, further highlighting its therapeutic potential in enhancing an antitumor immune response.


Subject(s)
CD8-Positive T-Lymphocytes , Carcinoma, Hepatocellular , Liver Neoplasms , Polylactic Acid-Polyglycolic Acid Copolymer , Animals , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Mice , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Mice, Inbred C57BL , Ovalbumin/immunology , Ovalbumin/chemistry , Programmed Cell Death 1 Receptor/immunology , Programmed Cell Death 1 Receptor/metabolism , Nanoparticles/chemistry , Cancer Vaccines/immunology , Cancer Vaccines/chemistry , Memory T Cells/immunology , Vaccination , Humans , RAW 264.7 Cells , Immunologic Memory
13.
Article in English | MEDLINE | ID: mdl-38770561

ABSTRACT

STUDY DESIGN: Retrospective review of cohort studies. OBJECTIVE: To clarify the necessary ODI improvement for patient satisfaction two years after lumbar surgery. BACKGROUND: Evaluating elective lumbar surgery care often involves patient-reported outcomes (PRO). While postoperative functional improvement measured by ODI is theoretically linked to satisfaction, conflicting evidence exists regarding this association. METHODS: Baseline ODI and 2-year postoperative ODI were assessed. Patient satisfaction, measured on a scale from 1 to 5, with scores ≥4 considered satisfactory, was evaluated. Patients with incomplete follow-up were excluded. Statistical analyses included Mann-Whitney-U and multivariable logistic regression adjusted for age, sex, and BMI. Receiver operating characteristic (ROC) analysis determined threshold values for ODI improvement and postoperative target ODI indicative of patient satisfaction. RESULTS: 383 patients were included (mean age 65±10 y, 57% female). ODI improvement was observed in 91% of patients, with 77% reporting satisfaction scores ≥4. Baseline ODI (median 62, IQR 46-74) improved to a median of 10 (IQR 1-10) 2 years postoperatively. Baseline (OR 0.98, P=0.015) and postoperative ODI scores (OR 0.93, P<0.001), as well as the difference between them (OR 1.04, P< 0.001), were significantly associated with patient satisfaction. Improvement of ≥38 ODI points or a relative change of ≥66% was indicative for patient satisfaction, with higher sensitivity (80%) and specificity (82%) for the relative change versus the absolute change (69%, 68%). With a sensitivity of 85% and a specificity of 77%, a postoperative target ODI of ≤24 indicated patient satisfaction. CONCLUSION: Lower baseline ODI and greater improvements in postoperative ODI are associated with an increased likelihood of patient satisfaction. A relative improvement of ≥66% or achieving a postoperative ODI score of ≤24 were the most indicative thresholds for predicting patient satisfaction, proving more sensitivity and specificity than an absolute change of ≥38 points.

14.
Small ; : e2401491, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38751305

ABSTRACT

The design and fabrication of a lithiophilic skeleton are highly important for constructing advanced Li metal anodes. In this work, a new lithiophilic skeleton is reported by planting metal sulfides (e.g., Ni3S2) on vertical graphene (VG) via a facile ultrafast Joule heating (UJH) method, which facilitates the homogeneous distribution of lithiophilic sites on carbon cloth (CC) supported VG substrate with firm bonding. Ni3S2 nanoparticles are homogeneously anchored on the optimized skeleton as CC/VG@Ni3S2, which ensures high conductivity and uniform deposition of Li metal with non-dendrites. By means of systematic electrochemical characterizations, the symmetric cells coupled with CC/VG@Ni3S2 deliver a steady long-term cycle within 14 mV overpotential for 1800 h (900 cycles) at 1 mA cm-2 and 1 mAh cm-2. Meanwhile, the designed CC/VG@Ni3S2-Li||LFP full cell shows notable electrochemical performance with a capacity retention of 92.44% at 0.5 C after 500 cycles and exceptional rate performance. This novel synthesis strategy for metal sulfides on hierarchical carbon-based materials sheds new light on the development of high-performance lithium metal batteries (LMBs).

15.
Polymers (Basel) ; 16(9)2024 May 01.
Article in English | MEDLINE | ID: mdl-38732731

ABSTRACT

Transparent polysiloxane elastomers with good self-healing and reprocessing abilities have attracted significant attention in the field of artificial skin and flexible displays. Herein, we propose a simple one-pot method to fabricate a room temperature self-healable polysiloxane elastomer (HPDMS) by introducing dynamic and reversible imine bonds and boroxine into polydimethylsiloxane (PDMS) networks. The presence of imine bonds and boroxine is proved by FT-IR and NMR spectra. The obtained HPDMS elastomer is highly transparent with a transmittance of up to 80%. The TGA results demonstrated that the HPDMS elastomer has good heat resistance and can be used in a wide temperature range. A lower glass transition temperature (Tg, -127.4 °C) was obtained and revealed that the elastomer is highly flexible at room temperature. Because of the reformation of dynamic reversible imine bonds and boroxine, the HPDMS elastomers exhibited excellent autonomous self-healing properties. After healing for 3 h, the self-healing efficiency of HPDMS reached 96.3% at room temperature. Moreover, the elastomers can be repeatedly reprocessed multiple times under milder conditions. This work provides a simple but effective method to prepare transparent self-healable and reprocessable polysiloxane elastomers.

16.
Life Sci ; 348: 122717, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38744419

ABSTRACT

The loss or dysfunction of pancreatic ß-cells, which are responsible for insulin secretion, constitutes the foundation of all forms of diabetes, a widely prevalent disease worldwide. The replacement of damaged ß-cells with regenerated or transplanted cells derived from stem cells is a promising therapeutic strategy. However, inducing the differentiation of stem cells into fully functional glucose-responsive ß-cells in vitro has proven to be challenging. Noncoding RNAs (ncRNAs) have emerged as critical regulatory factors governing the differentiation, identity, and function of ß-cells. Furthermore, engineered hydrogel systems, biomaterials, and organ-like structures possess engineering characteristics that can provide a three-dimensional (3D) microenvironment that supports stem cell differentiation. This review summarizes the roles and contributions of ncRNAs in maintaining the differentiation, identity, and function of ß-cells. And it focuses on regulating the levels of ncRNAs in stem cells to activate ß-cell genetic programs for generating alternative ß-cells and discusses how to manipulate ncRNA expression by combining hydrogel systems and other tissue engineering materials. Elucidating the patterns of ncRNA-mediated regulation in ß-cell biology and utilizing this knowledge to control stem cell differentiation may offer promising therapeutic strategies for generating functional insulin-producing cells in diabetes cell replacement therapy and tissue engineering.


Subject(s)
Cell Differentiation , Insulin-Secreting Cells , RNA, Untranslated , Tissue Engineering , Insulin-Secreting Cells/metabolism , Tissue Engineering/methods , Humans , RNA, Untranslated/genetics , Animals , Cell Differentiation/genetics , Stem Cells/metabolism , Stem Cells/cytology , Diabetes Mellitus/metabolism , Diabetes Mellitus/genetics , Diabetes Mellitus/therapy , Hydrogels
17.
Article in English | MEDLINE | ID: mdl-38717315

ABSTRACT

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To analyze the relationship of abdominal aortic calcification (AAC) and a reduction in the cross-sectional area (CSA) and the fatty infiltration (FI) of the paravertebral muscles in patients undergoing lumbar fusion surgery. BACKGROUND: Both AAC and paraspinal muscle degeneration have been shown to be associated with poorer outcomes after surgical treatment of degenerative diseases of the lumbar spine. However, there is a lack of data on the association between AAC and paraspinal muscle changes in patients undergoing spine surgery. METHODS: We retrospectively analyzed patients undergoing lumbar fusion for degenerative spinal pathologies. Muscular and spinal degeneration were measured on magnetic resonance imaging (MRI). AAC was classified on lateral lumbar radiographs. The association of AAC and paraspinal muscle composition was assessed by a multivariate regression analysis adjusted for age, sex, body mass index (BMI), comorbidities, and lumbar degeneration. RESULTS: A total of 301 patients was included. Patients with AAC showed significantly higher degrees of intervertebral disc and facet joint degeneration as well as higher total endplate scores at the L3/4 level. The univariable regression analysis showed a significant positive correlation between the degree of AAC and the FI of the erector spinae (b=0.530, P<0.001) and multifidus (b=0.730, P<0.001). The multivariable regression analysis showed a significant positive correlation between the degree of AAC and the FI of the erector spinae (b=0.270, P=0.006) and a significant negative correlation between the degree of AAC and the CSA of the psoas muscle (b=-0.260, P=0.003). CONCLUSION: This study demonstrates a significant and independent association between AAC and degeneration of the erector spinae and the psoas muscles in patients undergoing lumbar fusion. As both AAC and degeneration of paraspinal muscles impact postoperative outcomes negatively, preoperative assessment of AAC may aid in identifying patients at higher risk after lumbar surgery.

18.
Article in English | MEDLINE | ID: mdl-38819199

ABSTRACT

STUDY DESIGN: Retrospective Database review. OBJECTIVE: Analyze revisions of CDAs reported to the MAUDE database. SUMMARY OF BACKGROUND DATA: Cervical disc arthroplasty (CDA) has emerged as a motion-preserving alternative to anterior cervical discectomy and fusion (ACDF) for degenerative cervical disease, demonstrating comparable outcomes. Despite the availability of variable CDA designs, there is limited data on the specific complications of individual CDAs. The Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database has been used to systematically report complications associated with CDAs. However, data on specific reasons for CDA revision remains scarce. The purpose of this study is to compare common complications associated with revision for different CDAs. METHODS: The MAUDE database was queried from January 2005 to September 2023, including all nine FDA-approved CDAs. The full-text reports of each complication were categorized based on whether revision surgery was performed, the complications and the type of CDA collected and compared. RESULTS: A total of 678 revisions for nine CDAs were reported: Mobi-C (239), M6 (167), Prodisc-C (88), Prestige (60), PCM (44), Bryan (35), Secure (23), Simplify (21), and Discover (1). The top three complications associated with revision were migration (23.5%), neck pain (15.5%), and heterotopic ossification (6.6%). The most common complications per device were migration for Mobi-C (26.4%), Prodisc-C (21.3%), Prestige (24.6%), PCM (84.1%), Bryan (48.6%), Secure (30.4%), and Discover (100%). For M6, the most common complications associated with revision surgery were osteolysis (18.6%) and neck pain (18.6%), while neck pain (23.8%) was the most common for the Simplify. CONCLUSION: The MAUDE database highlights complications related to CDA revision in which the primary complications consistently include implant migration, neck pain, and heterotopic ossification ,varying in their rerelvance depending on the CDA.

19.
J Neurosurg Spine ; : 1-10, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701526

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the influence of preoperatively assessed paraspinal muscle parameters on postoperative patient-reported outcomes and maintenance of cervical sagittal alignment after anterior cervical discectomy and fusion (ACDF). METHODS: Patients with preoperative and postoperative standing cervical spine lateral radiographs and preoperative cervical MRI who underwent an ACDF between 2015 and 2018 were reviewed. Muscles from C3 to C7 were segmented into 4 functional groups: anterior, posteromedial, posterolateral, and sternocleidomastoid. The functional cross-sectional area and also the percent fat infiltration (FI) were calculated for all groups. Radiographic alignment parameters collected preoperatively and postoperatively included C2-7 lordosis and C2-7 sagittal vertical axis (SVA). Neck Disability Index (NDI) scores were recorded preoperatively and at 2 and 4-6 months postoperatively. To investigate the relationship between muscle parameters and postoperative changes in sagittal alignment, multivariable linear mixed models were used. Multivariable linear regression models were used to analyze the correlations between the changes in NDI scores and the muscles' FI. RESULTS: A total of 168 patients with NDI and 157 patients with sagittal alignment measurements with a median follow-up of 364 days were reviewed. The mixed models showed that a greater functional cross-sectional area of the posterolateral muscle group at each subaxial level and less FI at C4-6 were significantly associated with less progression of C2-7 SVA over time. Moreover, there was a significant correlation between greater FI of the posteromedial muscle group measured at the C7 level and less NDI improvement at 4-6 months after ACDF. CONCLUSIONS: The findings highlight the importance of preoperative assessment of the cervical paraspinal muscle morphology as a predictor for patient-reported outcomes and maintenance of C2-7 SVA after ACDF.

20.
Eur Spine J ; 33(5): 1737-1746, 2024 May.
Article in English | MEDLINE | ID: mdl-38801435

ABSTRACT

PURPOSE: This study aimed to investigate the impact of sarcopenia and lumbar paraspinal muscle composition (PMC) on patient-reported outcomes (PROs) after lumbar fusion surgery with 12-month follow-up (12 M-FU). METHODS: A prospective investigation of patients undergoing elective lumbar fusion was conducted. Preoperative MRI-based evaluation of the cross-sectional area (CSA), the functional CSA (fCSA), and the fat infiltration(FI) of the posterior paraspinal muscles (PPM) and the psoas muscle at level L3 was performed. Sarcopenia was defined by the psoas muscle index (PMI) at L3 (CSAPsoas [cm2]/(patients' height [m])2). PROs included Oswestry Disability Index (ODI), 12-item Short Form Healthy Survey with Physical (PCS-12) and Mental Component Scores (MCS-12) and Numerical Rating Scale back and leg (NRS-L) pain before surgery and 12 months postoperatively. Univariate and multivariable regression determined associations among sarcopenia, PMC and PROs. RESULTS: 135 patients (52.6% female, 62.1 years, BMI 29.1 kg/m2) were analyzed. The univariate analysis demonstrated that a higher FI (PPM) was associated with worse ODI outcomes at 12 M-FU in males. Sarcopenia (PMI) and higher FI (PPM) were associated with worse ODI and MCS-12 at 12 M-FU in females. Sarcopenia and higher FI of the PPM are associated with worse PCS-12 and more leg pain in females. In the multivariable analysis, a higher preoperative FI of the PPM (ß = 0.442; p = 0.012) and lower FI of the psoas (ß = -0.439; p = 0.029) were associated with a worse ODI at 12 M-FU after adjusting for covariates. CONCLUSIONS: Preoperative FI of the psoas and the PPM are associated with worse ODI outcomes one year after lumbar fusion. Sarcopenia is associated with worse ODI, PCS-12 and NRS-L in females, but not males. Considering sex differences, PMI and FI of the PPM might be used to counsel patients on their expectations for health-related quality of life after lumbar fusion.


Subject(s)
Lumbar Vertebrae , Paraspinal Muscles , Patient Reported Outcome Measures , Sarcopenia , Spinal Fusion , Humans , Male , Female , Sarcopenia/diagnostic imaging , Middle Aged , Lumbar Vertebrae/surgery , Lumbar Vertebrae/diagnostic imaging , Prospective Studies , Aged , Paraspinal Muscles/diagnostic imaging , Follow-Up Studies , Awards and Prizes
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