Research on Alkali-Activated Slag Stabilization of Dredged Silt Based on a Response Surface Method.

To improve the resource utilization of dredged silt and industrial waste, this study explores the efficacy of using ground granulated blast furnace slag (GGBS), active calcium oxide (CaO), and sodium silicate (Na2O·nSiO2) as alkali activators for silt stabilization. Through a combination of addition tests, response surface method experiments, and microscopic analyses, we identified key factors influencing the unconfined compressive strength (UCS) of stabilized silt, optimized material ratios, and elucidated stabilization mechanisms. The results revealed the following: (1) CaO exhibited the most pronounced stabilization effect, succeeded by Na2O·nSiO2, whereas GGBS alone displayed marginal efficacy. CaO-stabilized silt demonstrated rapid strength augmentation within the initial 7 d, while Na2O·nSiO2-stabilized silt demonstrated a more gradual strength enhancement over time, attributable to the delayed hydration of GGBS in non-alkaline conditions, with strength increments noticeably during later curing phases. (2) Response surface analysis demonstrated substantial interactions among GGBS-CaO and GGBS-Na2O·nSiO2, with the optimal dosages identified as 11.5% for GGBS, 4.1% for CaO, and 5.9% for Na2O·nSiO2. (3) X-ray diffraction (XRD) and scanning electron microscopy (SEM) analyses clarified that the hydration reactions within the GGBS-Na2O·nSiO2 composite cementitious system synergistically enhanced one another, with hydration products wrapping, filling, and binding the silt particles, thereby rendering the microstructure denser and more stable. Based on these experimental outcomes, we propose a microstructural mechanism model for the stabilization of dredged silt employing GGBS-CaO-Na2O·nSiO2.

A randomized, multicenter phase III Study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer.

BACKGROUND: F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). METHODS: This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. RESULTS: The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 - 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. CONCLUSIONS: A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04174599, on 22/11/2019.

Regulatory Network of the Late-Recruited Primary Decarboxylase C4NADP-ME in Sugarcane.

In agronomically important C4 grasses, efficient CO2 delivery to Rubisco is facilitated by NADP-malic enzyme (C4NADP-ME), which decarboxylates malate in bundle sheath cells. However, understanding the molecular regulation of the C4NADP-ME gene in sugarcane (Saccharum spp.) is hindered by its complex genetic background. Enzymatic activity assays demonstrated that decarboxylation in sugarcane Saccharum spontaneum predominantly relies on the NADP-ME pathway, similar to sorghum (Sorghum bicolor) and maize (Zea mays). Comparative genomics analysis revealed the recruitment of eight core C4 shuttle genes, including C4NADP-ME (SsC4NADP-ME2), in the C4 pathway of sugarcane. Contrasting to sorghum and maize, the expression of SsC4NADP-ME2 in sugarcane is regulated by different transcription factors (TFs). We propose a gene regulatory network for SsC4NADP-ME2, involving candidate TFs identified through gene co-expression analysis and yeast one-hybrid experiment. Among these, ABA INSENSITIVE5 (ABI5) was validated as the predominant regulator of SsC4NADP-ME2 expression, binding to a G-box within its promoter region. Interestingly, the core element ACGT within the regulatory G-box was conserved in sugarcane, sorghum, maize, and rice (Oryza sativa), suggesting an ancient regulatory code utilized in C4 photosynthesis. This study offers insights into SsC4NADP-ME2 regulation, crucial for optimizing sugarcane as a bioenergy crop.

Effects of Nicotinamide Adenine Dinucleotide on Older Patients with Heart Failure.

Background: Heart failure (HF) is the main cause of death in middle-aged and older people and is characterized by high morbidity, high mortality, a high rehospitalization rate, and many high-risk groups. Nicotinamide adenine dinucleotide (NAD+) is widely present in the mitochondria of cardiomyocytes and maintains the redox balance in the body, which can effectively treat HF. We sought to evaluate whether NAD+ therapy has some clinical efficacy in patients with HF. Methods: Based on using conventional drugs to treat HF, patients (n = 60) were randomized 1:1 to saline and 50 mg NAD+ with 50 mL of normal saline for 7 days. The baseline characteristics of patients before and after treatment and cardiac function (N-terminal pro B-type natriuretic peptide (NT-proBNP) level and left ventricular ejection fraction (LVEF) value) were analyzed. Serological analysis (sirtuin-1 (SIRT1), sirtuin-3 (SIRT3), sirtuin-6 (SIRT6), reactive oxygen species (ROS), and endothelin) was also performed. Results: Among the 60 patients with HF who were treated with NAD+ for 7 days, the improvement rate in NT-proBNP levels and LVEF values was better than in the saline group, although not statistically significant. These patients were more likely to benefit from NAD+ because of higher levels of anti-oxidative stress (SIRT1, SIRT3, SIRT6, and ROS) and anti-endothelial injury (endothelin) than those in the saline control group. Conclusions: According to the results of this study, it is believed that 7 days of NAD+ injections has a positive effect on improving cardiac function, oxidative stress, and endothelial injury in patients with HF compared with the saline control. Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/) ChiCTR2300074326; retrospectively registered on 3 August 2023.

Regional structural-functional connectivity coupling in major depressive disorder is associated with neurotransmitter and genetic profiles.

BACKGROUND: Abnormalities in structural-functional connectivity (SC-FC) coupling have been identified globally in patients with major depressive disorder (MDD). However, investigations have neglected the variability and hierarchical distribution of these abnormalities across different brain regions. Furthermore, the biological mechanisms underlying regional SC-FC coupling patterns are not well understood. METHODS: We enrolled 182 patients with MDD and 157 healthy control (HC) subjects, quantifying the intergroup differences in regional SC-FC coupling. The extreme gradient boosting (XGBoost), support vector machines (SVM) and random forest (RF) models were constructed to assess the potential of SC-FC coupling as biomarkers for MDD diagnosis and symptom prediction. Then, we examined the link between changes in regional SC-FC coupling in patients with MDD, neurotransmitter distributions, and gene expression. RESULTS: We observed increased regional SC-FC coupling in default mode network (T = 3.233) and decreased coupling in frontoparietal network (T = -3.471) in MDD relative to HC. XGBoost (AUC = 0.853), SVM (AUC = 0.832) and RF (p < 0.05) models exhibited good prediction performance. The alterations in regional SC-FC coupling in patients with MDD were correlated with the distributions of four neurotransmitters (p < 0.05) and expression maps of specific genes. These genes were strongly enriched in genes implicated in excitatory neurons, inhibitory neurons, cellular metabolism, synapse function, and immune signaling. These findings were replicated on two brain atlases. CONCLUSIONS: This work enhances our understanding of MDD and pave the way for the development of additional targeted therapeutic interventions.

Transjugular intrahepatic portosystemic shunt (TIPS) with variceal embolization reduces rebleeding risk for patients with portal pressure gradient over 12 mmHg: A long-term follow-up study.

OBJECTIVE: The consensus on whether Transjugular intrahepatic portosystemic shunt (TIPS) should be combined with variceal embolization in the treatment of portal hypertension-induced bleeding has not yet been reached. This study aimed to compare the difference in rebleeding incidence between TIPS and TIPS combined with variceal embolization and to analyze the optimal population for variceal embolization. METHODS: Clinical data of 721 patients undergoing TIPS were retrospectively collected. Patients were divided into two groups: TIPS alone (n = 155) and TIPS with embolization (TIPS+E, n = 251). Kaplan-Meier (KM) curves were used to analyze prognostic differences between the two groups, and subgroup analysis was conducted based on post-TIPS portal pressure gradient (PPG) exceeding 12 mmHg. RESULTS: After TIPS placement, the mean PPG significantly decreased for all patients. A total of 51 patients (12.6 %) experienced rebleeding, with 24 cases (15.9 %) in the TIPS group and 27 cases (10.6 %) in the TIPS+E group. There was no significant difference in cumulative rebleeding incidence between the TIPS+E and TIPS groups. In the subgroup with post-TIPS PPG greater than 12 mmHg, the cumulative rebleeding incidence was significantly lower in the TIPS+E group compared to the TIPS group (HR = 0.47, 95 %CI = 0.24-0.93, Log rank P = 0.026). No significant difference was found in patients with a post-TIPS PPG less than 12 mmHg. CONCLUSION: For patients with post-TIPS PPG exceeding 12 mmHg, simultaneous variceal embolization with TIPS placement significantly reduces the risk of rebleeding.

Prognostic prediction signature and molecular subtype for liver cancer: A CTC/CTM­related gene prediction model and independent external validation.

Liver cancer is the second leading cause of tumor-related death worldwide, and a serious threat to lives and health. Circulating tumor cells (CTCs) facilitate the progression of various cancers, including liver cancer. The relationship between CTC/circulating tumor microemboli-related genes (CRGs) and the prognosis of liver cancer is unclear. The aim of the present study was to identify CTC/circulating tumour microemboli-related genes (CRGs) in hepatocellular carcinoma and to investigate their clinical significance. Transcriptomic data from The Cancer Genome Atlas (International Cancer Genome Consortium (ICGC) and GSE117623 databases were combined, and differentially expressed CRGs were identified. These were subsequently analyzed via least absolute shrinkage and selection operator and multivariate Cox analyses, and a five-gene risk signature was constructed. The signature was validated in the ICGC and GSE14520 dataset with survival analysis and receiver operating characteristic curve analysis. Immunocyte infiltration, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE), and the somatic mutation rate were also compared between high- and low-risk groups, based on the median predictive index, to further evaluate the immunotherapeutic value of the model. Molecular subtypes of liver cancer were characterized by the non-negative matrix factorization method and potential therapeutic compounds were evaluated for different subtypes. Nomograms were utilized to predict the prognosis of patients, and the signature was compared with previous literature models. Additionally, the biological function of one of the CRGs, tumor protein p53 inducible protein 3 (TP53I3), in liver cancer was further explored through in vitro experiments. Analysis of the prognostic characteristics of the five CRGs led to the identification of two liver cancer subtypes. Patients in the low-risk group had a longer survival compared with those in the high-risk group, and patients in the latter group were associated with a higher TMB, immunocyte infiltration and somatic mutation rate, and lower TIDE scores. The prognostic profile was validated in the ICGC and GSE14520 datasets and exhibited a good predictive performance. In vitro analysis showed that the knockdown of TP53I3 suppressed liver cancer cell proliferation. In summary, CRGs were used to develop a new prognostic signature to predict the prognosis of patients with liver cancer. This signature may be used to assess the prognosis of patients and may provide new insights for clinical management strategies. In addition, TP53I3 is potentially a therapeutic target for liver cancer.

Enhanced efficacy of combined VEGFR peptide-drug conjugate and anti-PD-1 antibody in treating hepatocellular carcinoma.

This study aimed to design a VEGFR-targeting peptide-drug conjugate with the ability to decrease tumor burden and suppress tumor angiogenesis, and to further evaluate the therapeutic effect of anti-PD-1 antibody in HCC therapy. A VEGFR-targeting peptide VEGF125 - 136 (QR) was conjugated with a lytic peptide (KLU) to form a peptide-drug conjugate QR-KLU. And the efficacy of QR-KLU in combination with anti-PD-1 antibody for HCC therapy in vivo and in vitro were evaluated. QR-KLU inhibited the proliferation and migration of mouse HCC cell line (Hepa1-6) cells under normoxic and hypoxic conditions in a dose-dependent manner. In the subcutaneous Hepa1-6 tumor model, QR-KLU combined with the anti-PD-1 antibody substantially inhibited tumor growth, promoted tumor necrosis, and prolonged the survival time of tumor-bearing mice. QR-KLU substantially inhibited hypoxia-induced expression of VEGF, promoted tumor vascular normalization, and increased cluster of differentiation 8+ (CD8+) T cell infiltration in the tumor. In addition, QR-KLU and anti-PD-1 antibody demonstrated a strong synergistic effect in promoting the activation of intratumoral CD8+ T cells, reducing the expression of immune-inhibitory factors, and increasing the expression of immune-stimulatory factors. This study proposed a novel approach for enhancing the efficacy of anti-PD-1 antibody using a VEGFR-targeting peptide-drug conjugate in HCC therapy.

Interplay Between FoxM1 and Dab2 Promotes Endothelial Cell Responses in Diabetic Wound Healing.

Diabetes mellitus can cause impaired and delayed wound healing, leading to lower extremity amputations; however, the mechanisms underlying the regulation of vascular endothelial growth factor (VEGF)-dependent angiogenesis remain uncertain and could reveal new therapeutic targets. In our study, the molecular underpinnings of endothelial dysfunction in diabetes were investigated, focusing on the roles of Disabled-2 (Dab2) and Forkhead Box M1 (FoxM1) in VEGF receptor 2 (VEGFR2) signaling and endothelial cell (EC) function. Bulk RNA-sequencing analysis identified significant downregulation of Dab2 in high concentrations glucose treated primary mouse skin ECs, simulating hyperglycemic conditions in diabetes mellitus. In diabetic mice with a genetic EC deficiency of Dab2 angiogenesis was reduced in vivo and in vitro when compared with wild-type mice. Restoration of Dab2 expression by injected mRNA-containing lipid nanoparticles rescued impaired angiogenesis and wound healing in diabetic mice. At the same time, FoxM1 was downregulated in skin ECs subjected to high glucose conditions as determined by RNA-sequencing analysis. FoxM1 was found to bind to the Dab2 promoter, regulating its expression and influencing VEGFR2 signaling. The FoxM1 inhibitor FDI-6 reduced Dab2 expression and phosphorylation of VEGFR2. These findings indicate that restoring Dab2 expression through targeted therapies can enhance angiogenesis and wound repair in diabetes. To explore this therapeutic potential, we tested LyP-1-conjugated lipid nanoparticles (LNPs) containing Dab2 or control mRNAs to target ECs and found the former significantly improved wound healing and angiogenesis in diabetic mice. This study provides evidence of the crucial roles of Dab2 and FoxM1 in diabetic endothelial dysfunction and establishes targeted delivery as a promising treatment for diabetic vascular complications.

CAMK2G Promotes Neuronal Differentiation and Inhibits Migration in Neuroblastoma.

PURPOSE: Neuroblastoma (NB) originates from differentiation arrest of sympathoadrenal progenitors in the neural crest. It is necessary to reveal the differentiation mechanism of NB. Previously, we reported that Purkinje cell protein 4 (PCP4) is a well-differentiated marker of NB tissues. Herein, we explored the underlying mechanism of PCP4 induced differentiation in order to find better treatment options for patients. METHODS: We screened the interacting proteins of PCP4 by co-immunoprecipitation (Co-IP) and liquid chromatography-mass spectrometry (LC-MS/MS). Then we investigated the relevance between expression of calmodulin-dependent protein kinase II gamma (CAMK2G) and clinical features using R2 platform. We also explored the function of CAMK2G in NB cells by knockdown and RNA sequencing. RESULTS: Here, we verified the binding of PCP4 and calmodulin (CaM) by Co-IP and identified a target kinase of CaM, CAMK2G, by LC-MS/MS. PCP4 overexpression activates the autophosphorylation of CAMK2G. Patients with high CAMK2G expression had better survival while low CAMK2G was associated with unfavorable clinical features including MYCN-amplification, unfavorable histology, progression and high INSS stage. CAMK2G knockdown inhibited neurite outgrowth and down-regulated neuronal differentiation markers (NF-H, MAP2), yet promoted migration, invasion and proliferation. Gene Ontology (GO) analysis showed that knockdown of CAMK2G downregulated the expression of neuronal differentiation-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that knockdown of CAMK2G upregulated the expression of migration-related genes. CONCLUSION: These findings indicate that CAMK2G activated by PCP4/CaM complex promotes differentiation and inhibits migration in NB cells. LEVEL OF EVIDENCE: Not applicable.

Massive water production from lunar ilmenite through reaction with endogenous hydrogen.

Finding water resources is a crucial objective of lunar missions. However, both hydroxyl (OH) and natural water (H2O) have been reported to be scarce on the Moon. We propose a potential method for obtaining water on the Moon through H2O formation via endogenous reactions in lunar regolith (LR), specifically through the reaction FeO/Fe2O3 + H → Fe + H2O. This process is demonstrated using LR samples brought back by the Chang'E-5 mission. FeO and Fe2O3 are lunar minerals containing Fe oxides. Hydrogen (H) retained in lunar minerals from the solar wind can be used to produce water. The results of this study reveal that 51-76 mg of H2O can be generated from 1 g of LR after melting at temperatures above 1,200 K. This amount is ∼10,000 times the naturally occurring OH and H2O on the Moon. Among the five primary minerals in LR returned by the Chang'E-5 mission, FeTiO3 ilmenite contains the highest amount of H, owing to its unique lattice structure with sub-nanometer tunnels. For the first time, in situ heating experiments using a transmission electron microscope reveal the concurrent formation of Fe crystals and H2O bubbles. Electron irradiation promotes the endogenous redox reaction, which is helpful for understanding the distribution of OH on the Moon. Our findings suggest that the hydrogen retained in LR is a significant resource for obtaining H2O on the Moon, which is helpful for establishing a scientific research station on the Moon.

Molybdenum Nanoparticles Alleviate MC903-Induced Atopic Dermatitis-Like Symptoms in Mice by Modulating the ROS-Mediated NF-κB and Nrf2 /HO-1 Signaling Pathways.

Purpose: Atopic dermatitis (AD) is a chronic inflammatory skin condition that can affect individuals of all ages. Recent research has shown that oxidative stress plays a crucial role in the development of AD. Therefore, inhibiting oxidative stress may be an effective therapeutic approach for AD. Nano-molybdenum is a promising material for use as an antioxidant. We aimed to evaluate the therapeutic effects and preliminary mechanisms of molybdenum nanoparticles (Mo NPs) by using a murine model of chemically induced AD-like disease. Methods: HaCaT cells, a spontaneously immortalized human keratinocyte cell line, were stimulated by tumor necrosis factor-alpha /interferon-gamma after pre-treatment with Mo NPs. Reactive oxygen species levels, production of inflammatory factors, and activation of the nuclear factor kappa-B and the nuclear factor erythroid 2-related factor pathways were then evaluated. Mo NPs was topically applied to treat a murine model of AD-like disease induced by MC903, a vitamin D3 analog. Dermatitis scores, pruritus scores, transepidermal water loss and body weight were evaluated. AD-related inflammatory factors and chemokines were evaluated. Activation of the nuclear factor kappa-B and nuclear factor erythroid 2-related factor / heme oxygenase-1 pathways was assessed. Results: Our data showed that the topical application of Mo NPs dispersion could significantly alleviate AD skin lesions and itching and promote skin barrier repair. Further mechanistic experiments revealed that Mo NPs could inhibit the excessive activation of the nuclear factor kappa-B pathway, promote the expression of nuclear factor erythroid 2-related factor and heme oxygenase-1 proteins, and suppress oxidative stress reactions. Additionally, they inhibited the expression of thymic stromal lymphopoietin, inflammatory factors, and chemokines, thereby alleviating skin inflammation. Conclusion: Mo NPs present a promising alternative treatment option for patients with AD as they could address three pivotal mechanisms in the pathogenesis of AD concurrently.

Novel Role of Endothelial CD45 in Regulating Endothelial-to-Mesenchymal Transition in Atherosclerosis.

Background: Protein-tyrosine-phosphatase CD45 is exclusively expressed in all nucleated cells of the hematopoietic system but is rarely expressed in endothelial cells. Interestingly, our recent study indicated that activation of the endogenous CD45 promoter in human endothelial colony forming cells (ECFCs) induced expression of multiple EndoMT marker genes. However, the detailed molecular mechanisms underlying CD45 that drive EndoMT and the therapeutic potential of manipulation of CD45 expression in atherosclerosis are entirely unknown. Method: We generated a tamoxifen-inducible EC-specific CD45 deficient mouse strain (EC-iCD45KO) in an ApoE-deficient (ApoE-/-) background and fed with a Western diet (C57BL/6) for atherosclerosis and molecular analyses. We isolated and enriched mouse aortic endothelial cells with CD31 beads to perform single-cell RNA sequencing. Biomedical, cellular, and molecular approaches were utilized to investigate the role of endothelial CD45-specific deletion in the prevention of EndoMT in ApoE-/- model of atherosclerosis. Results: Single-cell RNA sequencing revealed that loss of endothelial CD45 inhibits EndoMT marker expression and transforming growth factor-ß signaling in atherosclerotic mice. which is associated with the reductions of lesions in the ApoE-/- mouse model. Mechanistically, the loss of endothelial cell CD45 results in increased KLF2 expression, which inhibits transforming growth factor-ß signaling and EndoMT. Consistently, endothelial CD45 deficient mice showed reduced lesion development, plaque macrophages, and expression of cell adhesion molecules when compared to ApoE-/- controls. Conclusions: These findings demonstrate that the loss of endothelial CD45 protects against EndoMT-driven atherosclerosis, promoting KLF2 expression while inhibiting TGFß signaling and EndoMT markers. Thus, targeting endothelial CD45 may be a novel therapeutic strategy for EndoMT and atherosclerosis.

B3GNT5 is a novel marker correlated with malignant phenotype and poor outcome in pancreatic cancer.

Pancreatic cancer (PC) is one of the most lethal malignancies and new therapeutic strategies are urgently needed. ß1,3-N-acetylglucosaminyltransferase V (B3GNT5) may be a potential option for cancer treatment, but its role in PC remains unknown. In this study, we first demonstrated through bioinformatics analysis that B3GNT5 was high expression in PC and predicted poor prognosis. We further constructed B3GNT5 overexpression or knockdown cell lines by employing lentivirus packaging techniques and confirmed that B3GNT5 could promote tumor cell viability and autonomous growth using cultured cells and vivo xenograft models. In addition, we found that knockdown of B3GNT5 in PC cells inhibited cell migration, invasion, and angiogenesis, as well as stemness of cancer stem cells and enhanced chemotherapy sensitivity to gemcitabine. Mechanistically, overexpression of the transcription factor STAT5B in PC cells enhanced the transcriptional activity of the B3GNT5 promoter. Our work confirmed a tumor-promotive role of B3GNT5 in PC pathogenesis.

Correlation Between Temporomandibular Joint Disc Perforation and Degenerative Joint Changes: A CBCT and Clinical Analysis.

OBJECTIVES: To analyse the correlation between temporomandibular joint (TMJ) disc perforation and degenerative joint changes (DJC) on cone-beam computed tomography (CBCT) and related factors. STUDY DESIGN: A total of 238 female patients with anterior disc displacement without reduction (ADDwoR), accounting for 348 affected joints, requiring TMJ disc open anchorage surgery were included in the study conducted from June 2021 to August 2022. Following TMJ disc open anchorage surgery, patients were divided into two groups: disc perforation (DP) and disc non-perforation (DNP). CBCT was utilised to assess different grades of condyle and articular eminence degenerative changes, and comparisons were made between the two groups regarding DJC and clinically relevant factors. RESULTS: In comparison with the DNP group, the DP group exhibited statistically significant differences in mid- and late-stage condyle bone degenerative changes and bone alterations of the articular eminence (odds ratio [OR] = 7.822; 95% CI [4.438-13.785]; p < 0.001 and OR = 5.575; 95% CI [3.128-9.936]; p < 0.001). Additionally, persistent joint sounds (OR = 1.932; 95% CI [1.011-3.691]; p = 0.046) and longer disease duration (OR = 4.901; 95% CI [2.395-10.028]; p < 0.001) demonstrated statistically significant differences. However, no significant differences were observed between the two groups in terms of age, joint pain and limited mouth opening. CONCLUSIONS: Bone degeneration changes in TMJ CBCT images are a high possible risk factor for DP. With an escalation in the degree of condyle degeneration, the risk of DP may increased correspondingly. Persistent joint sounds and extended duration of the disease were also confirmed to be noteworthy clinical risks of DP.

Melting and Rapid Solidification of Lunar Regolith Particles Returned by Chang'E-5 Mission.

Melting and solidification of lunar regolith are pivotal for comprehending the evolutionary dynamics of lunar volcanism, geology, and impact history. Additionally, insights gained from these processes can contribute to the advancement of in situ resource utilization technologies, for instance additive manufacturing and resource extraction systems. Herein, we conduct the direct observation of the melting and rapid solidification of lunar particles returned by the Chang'E 5 mission. The melting temperature and melting sequence were obtained. Bubble generation, growth, and release were clearly observed, with a maximum bubble diameter of 5 µm, which is supposed to be according to the release of volatiles that embedded in the particles. During the solidification process, evident crystallization occurred with incremental crystal growth rate approximately of 27 nm/s. Scanning electron microscopy and energy-dispersive x-ray spectroscopy results verified that the Fe-rich mineral crystalizes first. These results would improve the understanding of the evolution of lunar volcanism, geology, and impact history.

Association of autosomal mosaic chromosomal alterations with risk of bladder cancer in Chinese adults: a prospective cohort study.

Little is known about the prospective association between autosomal mosaic chromosomal alterations (mCAs), a group of large-scale somatic mutations on autosomes, and bladder cancer. Here we utilized data from 99,877 participants who were free of physician-diagnosed cancer at baseline (2004-2008) of the China Kadoorie Biobank to estimate the associations between autosomal mCAs and bladder cancer (ICD-10: C67). A total of 2874 autosomal mCAs events among 2612 carriers (2.6%) were detected. After a median follow-up of 12.4 years, we discovered that participants with all autosomal mCAs exhibited higher risks of bladder cancer, with a multivariable-adjusted hazard ratio (HR) (95% confidence interval [CI]) of 2.60 (1.44, 4.70). The estimate of such association was even stronger for mosaic loss events (HR [95% CI]: 6.68 [2.92, 15.30]), while it was not significant for CN-LOH events. Both expanded (cell fraction ≥10%) and non-expanded autosomal mCAs, as well as mosaic loss, were associated with increased risks of bladder cancer. Of interest, physical activity (PA) significantly modified the associations of autosomal mCAs and mosaic loss (Pinteraction = 0.038 and 0.012, respectively) with bladder cancer. The increased risks of bladder cancer were only observed with mCAs and mosaic loss among participants with a lower level of PA (HR [95% CI]: 5.11 [2.36, 11.09] and 16.30 [6.06, 43.81]), but not among participants with a higher level of PA. Our findings suggest that peripheral leukocyte autosomal mCAs may represent a novel risk factor for bladder cancer, and PA may serve as a potential intervention target for mCAs carriers.

RELATIONSHIP BETWEEN TRPM4 RS8104571 GENOTYPE, CIRCULATING TRPM4 AND SUR1, AND CLINICAL OUTCOME FOLLOWING TRAUMATIC BRAIN INJURY.

ABSTRACT: The variant single nucleotide polymorphism rs8104571 has been associated with poor outcomes following traumatic brain injury (TBI) and is most prevalent in those of African ancestry. This single nucleotide polymorphism (SNP) resides within a gene coding for the TRPM4 protein, which complexes with SUR1 protein to create a transmembrane ion channel and is believed to contribute to cellular swelling and cell death in neurological tissue. Our study evaluates the relationship between circulating TRPM4 and SUR1, rs8104571 genotype, and clinical outcome in TBI patients. Trauma patients with moderate to severe TBI were included in this retrospective study. rs8104571 genotyping and admission plasma TRPM4 and SUR1 quantification was performed with real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Adequate plasma for TRPM4 and SUR1 ELISA quantification was available for 289 patients, 54 of whom were African American (AA). Plasma TRPM4 concentration was increased in those with a variant rs8104571 allele compared to wild type when controlling for demographics and injury characteristics in the overall cohort (P = 0.04) and within the AA subgroup (P = 0.01). There was no significant association between plasma TRPM4 or SUR1 and clinical outcome (each P > 0.05). Plasma TRPM4 abundance increased with acute kidney injury severity (P = 0.02). The association between increased plasma TRPM4 and variant rs810457 supports an underlying mechanism involving increased neuroinflammation with a subsequent increase in the leakage of TRPM4 from the central nervous system into circulation. Alternative sources of plasma TRPM4 including the kidney cannot be excluded and may play a significant role in the pathophysiology of trauma as well.

Association of apolipoprotein A1 levels with lumbar bone mineral density and ß-CTX in osteoporotic fracture individuals: a cross-sectional investigation.

Background: The relationship between the levels of high-density lipoprotein (HDL) and bone mineral density (BMD) is controversial. Furthermore, the specific role of apolipoprotein A1 (APOA1), a primary HDL component, in regulating BMD remains unclear. This study aimed to elucidate the correlation between APOA1 levels and lumbar BMD in patients with osteoporotic fracture (OPF) for novel insights into potential therapeutic strategies against osteoporosis. Methods: This study included 587 OPF patients enrolled at the Kunshan Hospital, Affiliated with Jiangsu University between January 2017 and July 2022. The patient's serum APOA1 levels were determined, followed by the assessment of lumbar BMD and C-terminal telopeptide of type I collagen (ß-CTX) as outcome variables. The association of APOA1 levels with lumbar BMD and ß-CTX was assessed via Generalized Estimating Equations (GEE) and spline smoothing plot analyses. A generalized additive model (GAM) helped ascertain non-linear correlations. Moreover, a subgroup analysis was also conducted to validate the result's stability. Results: It was observed that APOA1 levels were positively correlated with lumbar BMD (ß = 0.07, 95% CI: 0.02 to 0.11, p = 0.0045), indicating that increased APOA1 levels were linked with enhanced lumbar BMD. Furthermore, APOA1 levels were negatively related to ß-CTX (ß = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003), suggesting APOA1 might reduce osteolysis. In addition, these findings were robustly supported by subgroup and threshold effect analyses. Conclusion: This study indicated that increased APOA1 levels were correlated with enhanced lumbar BMD and decreased osteolysis in OPF patients. Therefore, APOA1 may inhibit osteoclast activity to prevent further deterioration in osteoporotic patients. However, further research I warranted to validate these conclusions and elucidate the underlying physiologies.