Novel intervention for alcohol-associated liver disease.

A recently published article in the World Journal of Gastroenterology clarified that elafibranor, a dual peroxisome proliferator activated receptor α/δ (PPARα/δ) agonist, reduced inflammation and fibrosis in alcohol-associated liver disease (ALD). This letter aims to discuss the findings presented in that article. ALD is a global health problem, and no effective drugs has been approved by the Food and Drug Administration to cure it. Thus, finding targeted therapies is of great urgency. Herein, we focus on the pathogenesis of ALD and the role of PPARα/δ in its development. Consistent with the conclusion of the article of interest, we think that elafibranor may be a promising therapeutic option for ALD, due to the pivotal involvement of PPARα/δ in the pathogenesis of the disease. However, its treatment dose, timing, and side effects need to be further investigated in future studies.

An Ultrasensitive and Broad-Spectrum MoS2 Photodetector with Extrinsic Response Using Surrounding Homojunction.

As unique building blocks for advancing optoelectronics, 2D semiconducting transition metal dichalcogenides have garnered significant attention. However, most previously reported MoS2 photodetectors respond only to visible light with limited absorption, resulting in a narrow spectral response and low sensitivity. Here, a surrounding homojunction MoS2 photodetector featuring localized p-type nitrogen plasma doping on the surface of n-type MoS2 while preserving a high-mobility underlying channel for rapid carrier transport is engineered. The establishment of p-n homojunction facilitates the efficient separation of photogenerated carriers, thereby boosting the device's intrinsic detection performance. The resulting photoresponsivity is 6.94 × 104 A W-1 and specific detectivity is 1.21 × 1014 Jones @ 638 nm, with an optimal light on/off ratio of ≈107 at VGS = -27 V. Notably, the introduction of additional bands within MoS2 bandgap through nitrogen doping leads to an extrinsic broadband response to short-wave infrared. The device exhibits a photoresponsivity of 34 A W-1 and a specific detectivity of up to 5.92 × 1010 Jones @ 1550 nm. Furthermore, the high-performance broadband response is further demonstrated through imaging and integration with waveguides, paving the way for next generation of multifunctional imaging systems and high-performance photonic chips.

Innovative mesenchymal stem cell treatments for fatty liver disease.

The incidence of non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) is increasing year by year due to changes in the contemporary environment and dietary structure, and is an important public health problem worldwide. There is an urgent need to continuously improve the understanding of their disease mechanisms and develop novel therapeutic strategies. Mesenchymal stem cells (MSCs) have shown promise as a potential therapeutic strategy in therapeutic studies of NAFLD and ALD. NAFLD and ALD have different triggers and their specific mechanisms of disease progression are different, but both involve disease processes such as hepatocellular steatosis and potential fibrosis, cirrhosis, and even hepatocellular carcinoma. MSCs have metabolic regulatory, anti-apoptotic, antioxidant, and immunomodulatory effects that together promote liver injury repair and functional recovery, and have demonstrated positive results in preclinical studies. This editorial is a continuum of Jiang et al's review focusing on the advantages and limitations of MSCs and their derivatives as therapeutics for NAFLD and ALD. They detail how MSCs attenuate the progression of NAFLD by modulating molecular pathways involved in glucolipid metabolism, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. Based on recent advances, we discuss MSCs and their derivatives as therapeutic strategies for NAFLD and ALD, providing useful information for their clinical application.

Zoledronic Acid-Treated Rats Show Altered Jaw Histology and Gene Expression in Nonexposed Medication-Related Osteonecrosis of the Jaws.

BACKGROUND: Diagnosis and management of medication-related osteonecrosis of the jaws (MRONJ) prior to clinical exposure induced by trauma may lead to improved patient management. Currently, few studies have examined early histologic and molecular MRONJ-related changes in the jaws. PURPOSE: This study aimed to identify histological and gene expression changes in the maxilla and mandible of Sprague-Dawley (SD) rats after zoledronic acid (ZA) treatment. STUDY DESIGN, SETTING, AND SAMPLE: This was an in vivo animal study. The experiments were conducted in the laboratory at the Stomatology Hospital of Tianjin Medical University. A total of 12 SD rats were included. PREDICTOR VARIABLE: The predictor variable was ZA exposure. Twelve SD rats were divided into 2 groups: experimental (n = 6) and control (n = 6), and they were intraperitoneally injected with ZA and saline, respectively. MAIN OUTCOME VARIABLE: The outcome variables were histological and molecular changes. The maxilla, mandible, and ilium bone tissue samples were examined using Masson's trichrome and hematoxylin-eosin staining. Gene expression changes were identified using transcriptome sequencing, the Kyoto encyclopedia of genes and genomes, and gene interactome network analysis. The key changes were validated using the quantitative real-time polymerase chain reaction and immunohistochemistry. COVARIATES: None. ANALYSES: The t-test, χ2 test, and Fisher's exact probability method were used for statistical analyses using the Statistical Package for the Social Sciences software (version 26.0). RESULTS: All animals remained healthy during the experiments. Histological staining revealed that the percentage of empty bone lacunae in the maxilla and mandible was significantly higher than that in the ilium (P < .01). In total, 552 genes were screened using transcriptome sequencing. The sonic hedgehog (Shh) signaling pathway was highly enriched. The key gene for the Shh interaction was distal-less homeobox 5. The Shh, distal-less homeobox 5, and bone morphogenetic protein 2 genes and protein expression levels in the maxilla and mandible were higher in the experimental group than in the control group (P < .05). CONCLUSION AND RELEVANCE: MRONJ-induced osteonecrosis and gene expression changes precede trauma-induced clinical changes in the SD rat model. These findings may provide additional support for timely and clinically early diagnosis and intervention.

Long non-coding RNA Snhg15 promotes preosteoblast proliferation by interacting with and stabilizing nucleolin.

The proliferation and mineralization of preosteoblasts is crucial for bone formation and has attracted extensive attentions for decades. However, the roles of numerous long non-coding RNAs (lncRNAs) in preosteoblasts have not been fully determined. This study aimed to investigate the function of lncRNA Snhg15 in preosteoblasts as well as the potential underlying mechanism. LncRNA Snhg15 was dynamically expressed during preosteoblast proliferation and mineralization, and its transcripts were localized mainly in the cytoplasm. LncRNA Snhg15 knockdown significantly inhibited the proliferation and mineralization of preosteoblasts in both a cellular model and a murine ectopic bone formation model. RNA-seq showed that lncRNA Snhg15 knockdown downregulated multiple proliferation-related genes, and cell cycle deregulation was verified by flow cytometry. Mechanistically, we found that lncRNA Snhg15 could bind to nucleolin (NCL), thereby block NCL ubiquitination and decrease its degradation. Furthermore, the overexpression of NCL in lncRNA Snhg15-knockdown preosteoblasts ameliorated GO/G1 phase cell cycle arrest. Moreover, experiments in an in situ bone formation model confirmed the negative effects of lncRNA Snhg15 deficiency on bone formation. In conclusion, this study revealed an important regulatory role of lncRNA Snhg15/NCL complex in preosteoblast proliferation and may provide insights into the molecular mechanisms underlying bone formation.

Ultrahigh On/Off Ratio (110) Diamond Transistors with Exceptional Reproducibility of Normally Off Characteristics.

The development of monolithic integrated energy-efficient complementary circuits is crucial for the large-scale application of wide bandgap semiconductor-based high-frequency and high-power field-effect transistors (FETs). However, the inferior performance of p-channel FETs attributed to low hole density and mobility presents a substantial challenge. Diamond is a promising candidate due to its excellent comprehensive electrical properties and high thermal conductivity. Here, we report the fabrication of normally off diamond FETs based on a low work function metal gate and (110) hydrogen-terminated diamond with high hole density. The use of high-quality SiO2 layer ensures the complete depletion of the channel by the gate and offers high gating efficiency. Therefore, the developed devices demonstrate exceptional reproducibility of normally off characteristics with centrally distributed threshold voltages (-0.37 ± 0.3 V) and realize large current and voltage handling capabilities and low static standby power consumption in a synergic manner with record-high on/off ratio exceeding 1010, high current density (∼200 µA·µm-1), ultralow off-state current (∼fA·µm-1), and high breakdown voltage (-676 V). Additionally, the thermal desorption of negatively charged acceptors has been proven to significantly reduce carrier scattering. This work offers superior performance p-channel FETs for implementing energy-efficient complementary circuits, laying the groundwork for accelerated development in wide bandgap semiconductor power electronics.

CircHIPK3 regulates cementoblast differentiation via the miR-10b-5p/DOHH/NF-κB axis.

BACKGROUND: Intact cementum is vital for tooth stability and health. Cementoblasts, which line the root surface, are responsible for cementum formation. Recent evidence suggests that circular RNAs (circRNAs) are involved in various cellular functions and may have clinical applications. Although circHIPK3 has been shown to participate in osteogenesis, its role in cementoblast differentiation and mineralization is not well understood. METHODS: The ring structure of circHIPK3 was confirmed using Sanger sequencing and an actinomycin D assay. Subcellular localization of circHIPK3 was assessed using a nucleus-cytoplasm separation assay. RT-qPCR was employed to analyze circHIPK3 expression during cementoblast differentiation and following TNF-α treatment. In vivo, periapical lesions were induced in mouse mandibular first molars to mimic an inflammatory environment, and circHIPK3 expression was evaluated. The interaction of the circHIPK3/miR-10b-5p/DOHH axis was explored through RNA pull-down assays, bioinformatics analysis, and dual-luciferase reporter assays. The effects on cementoblast differentiation and mineralization were assessed by measuring osteogenic markers, alkaline phosphatase (ALP) activity, ALP staining, and alizarin red S staining. RESULTS: CircHIPK3 was predominantly located in the cytoplasm of cementoblasts, and its expression was significantly upregulated during cementoblast differentiation. Knockdown of circHIPK3 inhibited cementoblast differentiation and mineralization, whereas its overexpression promoted these processes. Mechanistically, circHIPK3 upregulated DOHH expression by sponging miR-10b-5p, thereby enhancing cementoblast differentiation and mineralization. The NF-κB pathway was found to act downstream of the circHIPK3/miR-10b-5p/DOHH axis in these processes. Additionally, circHIPK3 expression was significantly downregulated in inflammatory environments both in vitro and in vivo. Forced overexpression of circHIPK3 mitigated the inhibitory effects of TNF-α on cementoblast differentiation and mineralization. CONCLUSION: CircHIPK3 acts as a positive regulator of cementoblast differentiation and mineralization through the miR-10b-5p/DOHH/NF-κB axis, playing a crucial role in both normal and pathological cementogenesis.

The spinopelvic alignment in patients with prior knee or hip arthroplasty undergoing elective lumbar surgery.

BACKGROUND CONTEXT: Concurrent degeneration of the lumbar spine, hip, and knee can cause significant disability and lower quality of life. Osteoarthritis in the lower extremities can lead to movement limitations, possibly requiring total knee arthroplasty (TKA) or total hip arthroplasty (THA). These procedures often impact spinal posture, causing alterations in spinopelvic alignment and lumbar spine degeneration. It is unclear if patients with a history of prior total joint arthroplasty (TJA) have different spinopelvic alignment compared to patients without. PURPOSE: To assess the relationship between a history of previous THA or TKA, as well as combined THA and TKA, and the spinopelvic alignment in patients undergoing elective lumbar surgery for degenerative conditions. STUDY DESIGN: A retrospective analysis was conducted on patients who underwent lumbar surgery for degenerative conditions. The patients were stratified based on a history of TKA, THA, or both TKA and THA. PATIENT SAMPLE: A total of 632 patients (63% female) with an average age of 64±11 years and an average BMI of 30±6 kg/m2 were included. OUTCOME MEASURES: Patients were stratified based on a history of THA, TKA, or combined THA and TKA. Spinopelvic parameters (lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI)) were assessed. The relationship between spinopelvic alignment and prior TKA, THA or TKA and THA was analyzed METHODS: The data was tested for normal distribution using the Shapiro-Wilk test. We analyzed the relationship between the spinopelvic parameters and the different arthroplasty groups. Differences in scores between groups were examined using ANOVA. Tukey's Honestly Significant Difference test was used for pairwise comparison for significant ANOVA test results. Multivariable linear regression was applied, adjusted for age, sex and BMI. RESULTS: A total of 632 patients (63% female) were included in the study. Of these patients, 74 (12%) had a history of isolated TKA, 40 (6%) had prior isolated THA, and 15 (2%) had TKA and THA prior to lumbar surgery. Patients with prior arthroplasty were predominantly female (59%) and significantly older (68±7 years vs. 63±12 years, p<.001) with a significantly higher BMI (31±6 kg/m2 vs. 29±6 kg/m2, p<.001). The LL was significantly lower (45.0°±13 vs. 50.9°±14 p=.011) in the arthroplasty group compared to the nonarthroplasty group. A history of isolated TKA was significantly associated with lower LL (Est=-3.8, 95% CI -7.3 to -0.3, p=.031) and SS (Est=-2.6, 95% CI -5.0 to -0.2, p=.012) compared to patients without TJA. Prior combined THA and TKA was found to be significantly associated with a higher PT compared to the nonarthroplasty group (Est=5.1, 95% CI 0.4-9.8, p=.034). CONCLUSION: The spinopelvic alignment differs between patients with and without prior TJA who undergo elective lumbar surgery. The study shows that a history of TKA is significantly associated with a lower LL and SS. The combination of THA and TKA was associated with a significantly higher PT. These findings highlight the complex relationship between the hip, spine, and knee. Moreover, the results could aid in enhancing preoperative planning of lumbar surgery in patients with known TJA.

An Experimental and Simulation Study on the Formability of Commercial Pure Titanium Foil.

In order to understand the formability of as-received tempered commercial pure titanium grade 2 foils (CP Ti Gr2) with a thickness of 38 µm, a series of micro limited dome height (µ-LDH) tests were conducted in quasi-static speed (0.01 mm/s) at room temperature without the use of a lubricant. A technique developed at NIU was also used to create micro-circular grids (ϕ50 µm) on the as-received material. The forming limit curve (FLC) of the CP Ti Gr2 foils was obtained through the proposed µ-LDH test. For having mechanical properties of the CP Ti Gr2 foils for LS-Dyna FEA (Finite Element Analysis) simulations, a series of tensile tests in three directions were also conducted at room temperature with the same speed. The obtained FLC has been validated using a micro deep drawing case study in which both FEA simulations and experiments were conducted and compared. It has been proven in this study that the FLC obtained using the proposed µ-LDH test can be used for an extremely thin sheet-metal-forming process by the automotive, aerospace, medical, energy, and electronic industries, etc., right away for product design, forming process development, tool and die designs, and simulations, etc.

Pedicle Screw Placement with Augmented Reality Versus Robotic-Assisted Surgery.

STUDY DESIGN: This was a single-center prospective clinical and radiographic analysis of pedicle screw instrumentation with Robotic-assisted navigation (RAN) and augmented reality (AR). OBJECTIVE: This study aimed to compare the accuracy of lumbosacral pedicle screw placement with RAN versus AR. SUMMARY OF BACKGROUND DATA: RAN and AR have demonstrated superior accuracy in lumbar pedicle screw placement compared to conventional free-hand techniques. RAN and AR techniques both tout specific advantages over their counterparts, but to date, no study has directly compared the two technologies regarding pedicle screw accuracy. PATIENTS AND METHODS: Patients who underwent RAN or head-mounted AR navigated lumbosacral (L1-S1) pedicle screw placement for degenerative conditions were included. Screw accuracy was assessed by two independent reviewers on intraoperative 3D fluoroscopic scans using the Gertzbein and Robbins scale. A generalized linear mixed model was applied to evaluate the relationship between the screw placement technique and accuracy. RESULTS: 212 patients undergoing lumbosacral instrumentation with a total of 1,211 pedicle screws placed using RAN (n=108; screws= 827) or AR (n=104; screws= 384). Overall, Grade A was achieved in 92.6% of screws. No significant difference was found between RAN and AR screw placement regarding the incidence of accurate (Grade-A and -B screws; RAN n=824; 99.6% and AR n=379, 98.7%) versus inaccurate screws (Grade-C and -D screws; RAN n=3, 0.4% and AR n=5, 1.3%). When comparing "optimal" Grade-A screws (RAN n= 787, 95.2%, AR n=345, 89.8%) versus all other screws (B, C, and D), significantly higher accuracy was achieved using RAN (P=0.001). CONCLUSION: RAN and AR both achieved high accuracy in lumbosacral pedicle screw placement, proving reliable for this procedure. However, RAN resulted in significantly more Grade-A screw placements than AR.

The Association between prior arthroplasty and Paraspinal Muscle Degeneration in patients undergoing elective lumbar surgery.

PURPOSE: Spinal and lower extremity degeneration often causes pain and disability. Lower extremity osteoarthritis, eventually leading to total knee- (TKA) and -hip arthroplasty (THA), can alter posture through compensatory mechanisms, potentially causing spinal misalignment and paraspinal muscle (PM) atrophy. This study aims to evaluate the association between prior THA or TKA and PM-degeneration in patients undergoing elective lumbar surgery for degenerative conditions. METHODS: A retrospective analysis of patients undergoing lumbar surgery for degenerative conditions was conducted. Patients were categorized based on prior THA, TKA, or both. Quantitative analysis of functional cross-sectional area (fCSA) and fat infiltration (FI) of psoas, multifidus (MF), and erector spinae (ES) muscles at L4-level was performed using T2-weighted MRI images. The association between the FI and fCSA of the PM and prior arthroplasty was investigated. Differences were assessed using ANOVA and multivariable linear regression. RESULTS: Overall, 584 patients (60% female, 64 ± 12 years) were included. 66 patients (11%) had prior TKA, 36 patients (6%) THA, and 15 patients (3%) both TKA and THA. Patients with arthroplasty were mostly female (57%) and notably older (p < 0.001). The FI of the MF and the ES was significantly higher in the arthroplasty-group (both p < 0.001). Patients with prior TKA showed significantly higher FI (Est = 4.3%, p = 0.013) and lower fCSA (Est=-0.9 cm2, p = 0.012) in the MF compared to the non-arthroplasty-group. CONCLUSION: This study demonstrates a significant lower fCSA and higher FI in the MF among individuals with prior TKA. This highlights the complex knee-spine relationship and how these structures interact with each other.

Relationship between Lumbar Foraminal Stenosis and Multifidus Muscle Atrophy - A Retrospective Cross-Sectional Study.

STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVE: To evaluate the relationship between lumbar foraminal stenosis (LFS) and multifidus muscle atrophy. BACKGROUND: The multifidus muscle is an important stabilizer of the lumbar spine. In LFS, the compression of the segmental nerve can give rise to radicular symptoms and back pain. LFS can impede function and induce atrophy of the segmentally innervated multifidus muscle. METHODS: Patients with degenerative lumbar spinal conditions who underwent posterior spinal fusion for degenerative lumbar disease from December 2014 to February 2024 were analyzed. Multifidus fatty infiltration (FI) and functional cross-sectional area (fCSA) were determined at the L4 upper endplate axial level on T2- weighted MRI scans using dedicated software. Severity of LFS was assessed at all lumbar levels and sides using the Lee classification (Grade: 0 - 3). For each level, Pfirrmann and Weishaupt gradings were used to assess intervertebral disc disease (IVDD) and facet joint osteoarthritis (FJOA), respectively. Multivariable linear mixed models were run for the LFS grade of each level and side separately as the independent predictor of multifidus FI and fCSA. Each analysis was adjusted for age, sex, BMI, as well as FJOA and IVDD of the level corresponding to the LFS. RESULTS: A total of 216 patients (50.5% female) with a median age of 61.6 years (IQR=52.0 - 69.0) and a median BMI of 28.1 kg/m2 (IQR=24.8 - 33.0) were included. Linear mixed model analysis revealed that higher multifidus FI (Estimate [Confidence interval]=1.7% [0.1 - 3.3], P=0.043) and lower fCSA (-18.6 mm2 [-34.3 - -2.6], P=0.022) were both significantly predicted by L2-L3 level LFS severity. CONCLUSION: The observed positive correlation between upper segment LFS and multifidus muscle atrophy points towards compromised innervation. This necessitates further research to establish the causal relationship and guide prevention efforts.

MZT2A serves as a prognostic biomarker and promotes the progression of kidney renal clear cell carcinoma.

MZT2A is a novel core component in the γ-tubulin ring complex and aberrantly expressed in some types of tumors. However, MZT2A expression pattern across different cancers and its role in kidney renal clear cell carcinoma have not been sufficiently investigated. A thorough analysis of MZT2A expression landscape across 33 cancer types was conducted, utilizing 712 normal samples and 9807 tumor samples from TCGA (version 37.0), as well as 5112 normal samples from the GTEx databases. MZT2A's impact on KIRC cell viability and proliferation were evaluated through BrdU assays and monitored by cell imaging readers in MZT2A-expressing plasmid or siRNA-transfected cells. Additionally, the effects of MZT2A on cell apoptosis and cell cycle were detected using flow cytometry and Western blot. WGCNA analysis was employed to construct a co-expression gene network associated with MZT2A expression in KIRC, and Pearson correlation coefficient was utilized to examine the relationships between pairs of genes. MZT2A is overexpressed in 25 out of 33 types of cancer, including KIRC. In KIRC, high level of MZT2A was associated with higher clinical stage progression and poorer patients' survival. Downregulation of MZT2A decreased KIRC cell proliferation, retarded cell cycle and promoted apoptosis, while upregulation of MZT2A produced the opposite effects. WGCNA analysis and in vitro experiments revealed that MZT2A activated PI3K/AKT signaling pathway in KIRC. In all, MZT2A was overexpressed in most types of tumors. MZT2A served as an oncogene in KIRC and might be a potential target for guiding future treatments.

Multispectral smart window: Dynamic light modulation and electromagnetic microwave shielding.

A novel multispectral smart window has been proposed, which features dynamic modulation of light transmittance and effective shielding against electromagnetic microwave radiation. This design integrates liquid crystal dynamic scattering and dye doping techniques, enabling the dual regulation of transmittance and scattering within a single-layer smart window. Additionally, the precise control of conductive film thickness ensures the attainment of robust microwave signal shielding. We present a theoretical model for ion movement in the presence of an alternating electric field, along with a novel approach to manipulate negative dielectric constant. The proposed model successfully enables a rapid transition between light transparent, absorbing and haze states, with an optimum drive frequency adjustable to approximately 300 Hz. Furthermore, the resistive design of the conductive layer effectively mitigates microwave radiation within the 2-18 GHz range. These findings offer an innovative perspective for future advancements in environmental construction.

A bifunctional amylopullulanase of Streptococcus suis ApuA contributes to immune evasion by interaction with host complement C3b.

The complement system is the first defense line of the immune system. However, pathogens have evolved numerous strategies to evade complement attacks. Streptococcus suis is an important zoonotic bacterium, harmful to both the pig industry and human health. ApuA has been reported as a bifunctional amylopullulanase and also contributed to virulence of S. suis. Herein, we found that ApuA could activate both classical and alternative pathways of the complement system. Furthermore, by using bacterial two-hybrid, far-western blot and ELISA assays, it was confirmed that ApuA could interact with complement C3b. The interaction domain of ApuA with C3b was found to be its α-Amylase domain (ApuA_N). After construction of an apuA mutant (ΔapuA) and its complementary strain, it was found that compared to the wild-type strain (WT), ΔapuA had significantly increased C3b deposition and membrane attack complex formation. Additionally, ΔapuA showed significantly lower survival rates in human serum and blood and was more susceptible to engulfment by neutrophils and macrophages. Mice infected with ΔapuA had significantly higher survival rates and lower bacterial loads in their blood, lung and brains, compared to those infected with WT. In summary, this study identified ApuA as a novel factor involved in the complement evasion of S. suis and suggested its multifunctional role in the pathogenesis of S. suis.

Bone turnover markers in the preoperative assessment of bone quality - A prospective investigation of bone microstructure and advanced glycation endproducts in lumbar fusion patients.

INTRODUCTION: Effective tools to evaluate bone quality preoperatively are scarce and the standard method to determine bone quality requires an invasive biopsy. A non-invasive, and preoperatively available method for bone quality assessment would be of clinical value. The purpose of this study is to investigate the associations of bone formation marker, serum bone alkaline phosphatase (BAP), and bone resorption marker, urine collagen cross-linked N-telopeptide (uNTX) to volumetric bone mineral density (vBMD), fluorescent advanced glycation endproducts (fAGEs) and bone microstructure. MATERIALS AND METHODS: A cross-secional analysis using prospective data of patients undergoing lumbar spinal fusion was performed. BAP and uNTX were preoperatively collected. Quantitative computed tomography (QCT) was performed at the lumbar spine (vBMD ≤ 120 mg/cm3 osteopenic/osteoporotic). Bone biopsies from the posterior superior iliac spine were obtained and evaluated with multiphoton fluorescence microscopy for fAGEs and microcomputed tomography (µCT) for bone microarchitecture. Correlations between BAP/uNTX to vBMD, fAGEs and µCT parameters were assessed with Spearman's ρ. Receiver operating characteristic (ROC) analysis evaluated BAP and uNTX as predictors for osteopenia/osteoporosis. Multivariable linear regression models adjusting for age, sex, BMI, race and diabetes mellitus determined associations between BAP/uNTX and fAGEs. RESULTS: 127 prospectively enrolled patients (50.4% female, 62.5 years, BMI 28.7 kg/m2) were analyzed. uNTX (ρ=-0.331,p < 0.005) and BAP (ρ=-0.245,p < 0.025) decreased with cortical fAGEs, and uNTX (ρ=-0.380,p < 0.001) decreased with trabecular fAGEs. BAP and uNTX revealed no significant correlation with vBMD. ROC analysis for BAP and uNTX discriminated osteopenia/osteoporosis with AUC of 0.477 and 0.561, respectively. In the multivariable analysis, uNTX decreased with increasing trabecular fAGEs after adjusting for covariates (ß = 0.923;p = 0.031). CONCLUSION: This study demonstrated an inverse association of bone turnover markers and fAGEs. Both uNTX and BAP could not predict osteopenia/osteoporosis in the spine. uNTX reflects collagen characteristics and might have a complementary role to vBMD, as a non-invasive tool for bone quality assessment in spine surgery.

Diamond-Reinforced Al(H2PO4)3@Epoxy Hybrid Thermal Adhesive With Ultra-High Thermal Conductivity and Bonding Strength.

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.

Integrative analysis of aging-related genes reveals CEBPA as a novel therapeutic target in non-small cell lung cancer.

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.

Giant thermal conductivity and strain thermal response of nitrogen substituted diamane: a machine-learning-based prediction.

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.

Copper-Catalyzed Diastereo-, Enantio-, and (Z)-Selective Aminoallylation of Ketones through Reductive Couplings of Azatrienes for the Synthesis of Allylic 1,2-Amino Tertiary Alcohols.

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.