Zoledronic Acid and Enriched Autologous Bone Marrow Stem Cell Implantation for Femoral Head Osteonecrosis.

Purpose: This study evaluated the clinical results of zoledronic acid in the treatment of early osteonecrosis of the femoral head (ONFH). Materials and Methods: Study retrospectively analyzed 60 patients with zoledronic acid with bone marrow stem cell (BMSC) implantation (The study group) and 64 patients with BMSC implantation (The control group). The primary evaluation index included VAS, HHS, collapsed rate, and total hip replacement arthroplasty (THA) conversion rate. Results: The study group had a lower VAS (1.12 ± 0.22 vs 1.44 ± 0.32) and higher HHS (75.07 ± 3.66 vs 68.78 ± 2.24) compared to the control group in 6 months after surgery (P < 0.05). In the study group, 12 hips (20%) collapsed, and 7 of 60 hips (11.67%) required THA surgery at the last follow-up. However, 25 hips (38.8%) collapsed in the control group, and 19 hips (29.69%) required THA surgery. The study group had a lower collapsed rate (P = 0.029) and THA conversion rate (P = 0.016) in survival analysis. Conclusion: Zoledronic acid and BMSC implantation in the treatment of early ONFH is safe and effective, reduces pain shortens recovery time, and reduces collapsed rate and THA conversion rate in ONFH patients.

Meaningful nomograms based on systemic immune inflammation index predicted survival in metastatic pancreatic cancer patients receiving chemotherapy.

OBJECTIVE: The purpose of the study is to construct meaningful nomogram models according to the independent prognostic factor for metastatic pancreatic cancer receiving chemotherapy. METHODS: This study is retrospective and consecutively included 143 patients from January 2013 to June 2021. The receiver operating characteristic (ROC) curve with the area under the curve (AUC) is utilized to determine the optimal cut-off value. The Kaplan-Meier survival analysis, univariate and multivariable Cox regression analysis are exploited to identify the correlation of inflammatory biomarkers and clinicopathological features with survival. R software are run to construct nomograms based on independent risk factors to visualize survival. Nomogram model is examined using calibration curve and decision curve analysis (DCA). RESULTS: The best cut-off values of 966.71, 0.257, and 2.54 for the systemic immunological inflammation index (SII), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) were obtained by ROC analysis. Cox proportional-hazards model revealed that baseline SII, history of drinking and metastasis sites were independent prognostic indices for survival. We established prognostic nomograms for primary endpoints of this study. The nomograms' predictive potential and clinical efficacy have been evaluated by calibration curves and DCA. CONCLUSION: We constructed nomograms based on independent prognostic factors, these models have promising applications in clinical practice to assist clinicians in personalizing the management of patients.

Reversible acetylation of HDAC8 regulates cell cycle.

HDAC8, a member of class I HDACs, plays a pivotal role in cell cycle regulation by deacetylating the cohesin subunit SMC3. While cyclins and CDKs are well-established cell cycle regulators, our knowledge of other regulators remains limited. Here we reveal the acetylation of K202 in HDAC8 as a key cell cycle regulator responsive to stress. K202 acetylation in HDAC8, primarily catalyzed by Tip60, restricts HDAC8 activity, leading to increased SMC3 acetylation and cell cycle arrest. Furthermore, cells expressing the mutant form of HDAC8 mimicking K202 acetylation display significant alterations in gene expression, potentially linked to changes in 3D genome structure, including enhanced chromatid loop interactions. K202 acetylation impairs cell cycle progression by disrupting the expression of cell cycle-related genes and sister chromatid cohesion, resulting in G2/M phase arrest. These findings indicate the reversible acetylation of HDAC8 as a cell cycle regulator, expanding our understanding of stress-responsive cell cycle dynamics.

The Effect of Technology-Based Home Cardiac Rehabilitation on Risk Factor Modifications in Coronary Heart Disease Patients. A Systematic Review and Meta-Analysis.

Background: The delivery channels and approaches related to cardiac rehabilitation (CR), such as eHealth, mHealth, and telehealth, are evolving. Several studies have identified their effects on patients with coronary heart disease, although no studies have focused on all the approaches collectively. Methods: Randomized controlled trials have investigated lipid profiles, through systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI). Stata software was used for analysis, while Egger's linear regression test and Begg's funnel plot were also applied. Results: Technology-based home CR revealed significantly lower total cholesterol (TC) levels (standardized mean difference (SMD) = -0.19; 95% confidence interval [CI]: [-0.27, -0.11]); triglyceride (TG) levels (SMD = -0.26; 95% CI: [-0.35, 0.17]); low-density lipoprotein (LDL) levels (SMD = -0.18; 95% CI: [ -0.25, -0.11]); SBP (SMD = -0.26; 95% CI: [-0.33, -0.19]); DBP (SMD = -0.24; 95% CI: [-0.32, -0.16]); BMI (SMD = -0.12; 95% CI: [-0.18, -0.05]), and improved high-density lipoprotein (HDL) levels (SMD = 0.22; 95% CI: [0.14, 0.31]). Conclusions: Technology-based home CR can be used to lower TC, TG, and LDL levels, alongside the BMI, SBP, and DBP indexes, while also raising HDL levels; thus, its use should be widely promoted.

Radiocapitellar joint plasty for missed monteggia fracture with radial head deformity in children: a retrospective study.

Purpose: The retrospective study reviewed the clinical and radiological outcomes of patients treated with radiocapitellar joint plasty. Methods: 10 children with missed Monteggia fracture (MMF) were reviewed. The average time from injury to operation was 20 months. The average age of children who underwent the operation was 10.5 years. 6 flat and 4 domed radial heads were included. 7 type I and 3 type III MMF were identified based on the Bado classification. All children with MMF were treated by open radial head reduction with radiocapitellar joint plasty and ulnar osteotomy (UO). Results: The average union time was 4.9 ± 2.6 months. The average osteotomy angle to reduce the radial head was 15.7 ± 3.5°, and the average lengthening of the ulna was 8.2 ± 3.2 mm. The average preoperative flexion range of motion was 110.5 ± 9.1°, and the postoperative flexion range of motion was 138.8 ± 15.1° (p < 0.05). The average preoperative extension range of motion was 10.1 ± 3.2°, and the postoperative extension range of motion was 5.5 ± 3.3° (p < 0.05). The average preoperative pronation range of motion was 78.8 ± 8.7°, while the postoperative pronation range of motion was 81.1 ± 5.6° (p > 0.05). The average preoperative supination range of motion was 68.3 ± 9.7°, and the postoperative supination range of motion was 80.1 ± 7.8° (p < 0.05). The preoperative Kim score was 66.5 ± 10.9°, and the postoperative Kim score was 88.1 ± 12.6 (p < 0.05). The radial head was completely reduced in 9 patients, and subluxation in 1 patient. Osteoarthritis of the radiocapitellar joint was observed in 2 patients. Conclusions: Radiocapitellar joint plasty is effective surgical intervention for MMF with radial head deformity. It yields favorable functional outcomes while ensuring continued radial head reduction.

Discovery of Potent Selective HDAC6 Inhibitors with 5-Phenyl-1H-indole Fragment: Virtual Screening, Rational Design, and Biological Evaluation.

Among the HDACs family, histone deacetylase 6 (HDAC6) has attracted extensive attention due to its unique structure and biological functions. Numerous studies have shown that compared with broad-spectrum HDACs inhibitors, selective HDAC6 inhibitors exert ideal efficacy in tumor treatment with insignificant toxic and side effects, demonstrating promising clinical application prospect. Herein, we carried out rational drug design by integrating a deep learning model, molecular docking, and molecular dynamics simulation technology to construct a virtual screening process. The designed derivatives with 5-phenyl-1H-indole fragment as Cap showed desirable cytotoxicity to the various tumor cell lines, all of which were within 15 µM (ranging from 0.35 to 14.87 µM), among which compound 5i had the best antiproliferative activities against HL-60 (IC50 = 0.35 ± 0.07 µM) and arrested HL-60 cells in the G0/G1 phase. In addition, 5i exhibited better isotype selective inhibitory activities due to the potent potency against HDAC6 (IC50 = 5.16 ± 0.25 nM) and the reduced inhibitory activities against HDAC1 (selective index ≈ 124), which was further verified by immunoblotting results. Moreover, the representative binding conformation of 5i on HDAC6 was revealed and the key residues contributing 5i's binding were also identified via decomposition free-energy analysis. The discovery of lead compound 5i also indicates that virtual screening is still a beneficial tool in drug discovery and can provide more molecular skeletons with research potential for drug design, which is worthy of widespread application.

Comprehensive Proteogenomic Profiling Reveals the Molecular Characteristics of Colorectal Cancer at Distinct Stages of Progression.

Colorectal cancer (CRC) is the second most common malignant tumor world-wide. Analysis of the changes that occur during CRC progression could provide insights into the molecular mechanisms driving CRC development and identify improved treatment strategies. Here, we performed an integrated multi-omics analysis of 435 trace-tumor-samples from 148 colorectal cancer (CRC) patients, covering non-tumor (NT), intraepithelial neoplasia (IEN), infiltration (IFT), and advanced-stage CRC (A-CRC) phases. Proteogenomics analyses demonstrated that KRAS and BRAF mutations were mutually exclusive and elevated oxidation phosphorylation in the IEN phase. Chr17q loss and chr20q gain were also mutually exclusive, occurred predominantly in the IEN and IFT phases, respectively, and impacted the cell cycle. Mutation of TP53 was frequent in the A-CRC phase and associated with tumor microenvironment, including increased extracellular matrix rigidity and stromal infiltration. Analysis of the profiles of CRC based on CMS and CRIS classifications revealed the progression paths of each subtype and indicated that microsatellite instability was associated with specific subtype classifications. Additional comparison of molecular characteristics of CRC based on location showed that ANKRD22 amplification by chr10q23.31 gain enhanced glycolysis in the right-sided CRC. The AOM/DSS-induced CRC carcinogenesis mouse model in mice indicated that DDX5 deletion due to chr17q loss promoted CRC development, consistent with the findings from the patient samples. Collectively, this study provides an informative resource for understanding the driving events of different stages of CRC and identifying the potential therapeutic targets.

Multilineage-differentiating stress-enduring cells: a powerful tool for tissue damage repair.

Multilineage-differentiating stress-enduring (Muse) cells are a type of pluripotent cell with unique characteristics such as non-tumorigenic and pluripotent differentiation ability. After homing, Muse cells spontaneously differentiate into tissue component cells and supplement damaged/lost cells to participate in tissue repair. Importantly, Muse cells can survive in injured tissue for an extended period, stabilizing and promoting tissue repair. In addition, it has been confirmed that injection of exogenous Muse cells exerts anti-inflammatory, anti-apoptosis, anti-fibrosis, immunomodulatory, and paracrine protective effects in vivo. The discovery of Muse cells is an important breakthrough in the field of regenerative medicine. The article provides a comprehensive review of the characteristics, sources, and potential mechanisms of Muse cells for tissue repair and regeneration. This review serves as a foundation for the further utilization of Muse cells as a key clinical tool in regenerative medicine.

A radiomics-based nomogram may be useful for predicting telomerase reverse transcriptase promoter mutation status in adult glioblastoma.

BACKGROUND AND PURPOSE: As a crucial diagnostic and prognostic biomarker, telomerase reverse transcriptase (TERT) promoter mutation holds immense significance for personalized treatment of patients with glioblastoma (GBM). In this study, we developed a radiomics nomogram to determine the TERT promoter mutation status and assessed its prognostic efficacy in GBM patients. METHODS: The study retrospectively included 145 GBM patients. A comprehensive set of 3736 radiomics features was extracted from preoperative magnetic resonance imaging, including T2-weighted imaging, T1-weighted imaging (T1WI), contrast-enhanced T1WI, and fluid-attenuated inversion recovery. The construction of the radiomics model was based on integrating the radiomics signature (rad-score)with clinical features. Receiver-operating characteristic curve analysis was employed to evaluate the discriminative ability of the prediction model, and the risk score was used to stratify patient outcomes. RESULTS: The least absolute shrinkage and selection operator classifier identified 10 robust features for constructing the prediction model, and the radiomics nomogram exhibited excellent performance in predicting TERT promoter mutation status, with area under the curve values of.906 (95% confidence interval [CI]:.850-.963) and.899 (95% CI:.708-.966) in the training and validation sets, respectively. The clinical utility of the radiomics nomogram is further supported by calibration curve and decision curve analyses. Additionally, the radiomics nomogram effectively stratified GBM patients with significantly different prognoses (HR = 1.767, p = .019). CONCLUSION: The radiomics nomogram holds promise as a modality for evaluating TERT promoter mutations and prognostic outcomes in patients with GBM.

Downregulation of UBB potentiates SP1/VEGFA-dependent angiogenesis in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) presents a unique profile characterized by high levels of angiogenesis and robust vascularization. Understanding the underlying mechanisms driving this heterogeneity is essential for developing effective therapeutic strategies. This study revealed that ubiquitin B (UBB) is downregulated in ccRCC, which adversely affects the survival of ccRCC patients. UBB exerts regulatory control over vascular endothelial growth factor A (VEGFA) by directly interacting with specificity protein 1 (SP1), consequently exerting significant influence on angiogenic processes. Subsequently, we validated that DNA methyltransferase 3 alpha (DNMT3A) is located in the promoter of UBB to epigenetically inhibit UBB transcription. Additionally, we found that an unharmonious UBB/VEGFA ratio mediates pazopanib resistance in ccRCC. These findings underscore the critical involvement of UBB in antiangiogenic therapy and unveil a novel therapeutic strategy for ccRCC.

Impact of pre-meal immersion on multi-scale structural changes and starch digestibility of cooked dried noodles.

Pre-meal immersion is a common process for both the consumption of dried noodles and development of takeaway noodles, but its impact on the structure and digestibility of dried noodles is still unclear. In this study, dried noodles cooked for the optimal time were immersed at 80 °C for different time durations. Multi-scale structural changes, including texture, molecular structure, microstructure, and in vitro starch digestibility were studied using a combination of kinetic (first-order exponential decay function, the Peleg model, and LOS plots), physicochemical, and microscopic analysis. The relationship between multi-scale structural changes and starch digestibility was derived. As the immersion progressed, the hardness first rapidly decayed and then reached equilibrium. The decay rate in the initial stage depended on the gluten content. In most cases, the immersion process caused depolymerization of gluten proteins and further gelatinization of starch granules, which was observed from an increase in the free -SH content and decrease in the short-range ordered structure, although there were fluctuations over immersion time. Structural changes resulted in the corresponding changes in substance migration. However, a high gluten content (∼15% w/w) imparted a denser microstructure to the noodles, weakening the deterioration effects compared with a low gluten content (∼10% w/w). In vitro digestion experiments proved that samples with higher gluten content had higher starch digestion rates and lower starch digestion extent during immersion. Correlation analysis revealed that there was a negative correlation between k1 and the tightness of the gel. This study helps to reveal the structural mechanisms of starch digestibility in cooked noodles during immersion.

INTEDE 2.0: the metabolic roadmap of drugs.

The metabolic roadmap of drugs (MRD) is a comprehensive atlas for understanding the stepwise and sequential metabolism of certain drug in living organisms. It plays a vital role in lead optimization, personalized medication, and ADMET research. The MRD consists of three main components: (i) the sequential catalyses of drug and its metabolites by different drug-metabolizing enzymes (DMEs), (ii) a comprehensive collection of metabolic reactions along the entire MRD and (iii) a systematic description on efficacy & toxicity for all metabolites of a studied drug. However, there is no database available for describing the comprehensive metabolic roadmaps of drugs. Therefore, in this study, a major update of INTEDE was conducted, which provided the stepwise & sequential metabolic roadmaps for a total of 4701 drugs, and a total of 22 165 metabolic reactions containing 1088 DMEs and 18 882 drug metabolites. Additionally, the INTEDE 2.0 labeled the pharmacological properties (pharmacological activity or toxicity) of metabolites and provided their structural information. Furthermore, 3717 drug metabolism relationships were supplemented (from 7338 to 11 055). All in all, INTEDE 2.0 is highly expected to attract broad interests from related research community and serve as an essential supplement to existing pharmaceutical/biological/chemical databases. INTEDE 2.0 can now be accessible freely without any login requirement at: http://idrblab.org/intede/.

Comprehensive analysis of the prognostic values and immune implication of ESYT3 in lung adenocarcinoma.

Few studies have reported the association between ESYT3 and tumors. The purpose of this study was to investigate the molecular features and potential roles of ESYT3 in lung adenocarcinoma (LUAD). In the present study, GEPIA, UALCAN, TCGA databases, and KM Plotter were primarily used to study ESYT3 mRNA expression profiles and prognostic values in patients with LUAD. Then we evaluated co-expressed genes of ESYT3 by cBioPortal online tools and performed enrichment analysis using Metascape. Moreover, the relationship between ESYT3 and immune infiltrating cells was explored via TIMER2, and MethSurv database was used to conduct methylation analysis. We found ESYT3 was downregulated in LUAD tissues based on TCGA and GEPIA databases. Low expression of ESYT3 mRNA was observed to be significantly correlated with N classification and stage classification. GEPIA2, UALCAN databases and KM Plotter showed that low expression levels of ESYT3 was associated with poor survival in LUAD patients. The enrichment analysis indicated that co-expressed genes of ESYT3 were highly enriched in cell division. Then, our study showed ESYT3 was correlated with immune infiltration and immune checkpoints. Additionally, hypomethylation was associated with low ESYT3 expression and poor prognosis in LUAD. In conclusion, this study suggested ESYT3 could be a potential prognostic marker and a promising therapeutic target in LUAD.

Adaptive evolution of the enigmatic Takakia now facing climate change in Tibet.

The most extreme environments are the most vulnerable to transformation under a rapidly changing climate. These ecosystems harbor some of the most specialized species, which will likely suffer the highest extinction rates. We document the steepest temperature increase (2010-2021) on record at altitudes of above 4,000 m, triggering a decline of the relictual and highly adapted moss Takakia lepidozioides. Its de-novo-sequenced genome with 27,467 protein-coding genes includes distinct adaptations to abiotic stresses and comprises the largest number of fast-evolving genes under positive selection. The uplift of the study site in the last 65 million years has resulted in life-threatening UV-B radiation and drastically reduced temperatures, and we detected several of the molecular adaptations of Takakia to these environmental changes. Surprisingly, specific morphological features likely occurred earlier than 165 mya in much warmer environments. Following nearly 400 million years of evolution and resilience, this species is now facing extinction.

Development and validation a prognostic model based on natural killer T cells marker genes for predicting prognosis and characterizing immune status in glioblastoma through integrated analysis of single-cell and bulk RNA sequencing.

BACKGROUND: Glioblastoma (GBM) is an aggressive and unstoppable malignancy. Natural killer T (NKT) cells, characterized by specific markers, play pivotal roles in many tumor-associated pathophysiological processes. Therefore, investigating the functions and complex interactions of NKT cells is great interest for exploring GBM. METHODS: We acquired a single-cell RNA-sequencing (scRNA-seq) dataset of GBM from Gene Expression Omnibus (GEO) database. The weighted correlation network analysis (WGCNA) was employed to further screen genes subpopulations. Subsequently, we integrated the GBM cohorts from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases to describe different subtypes by consensus clustering and developed a prognostic model by least absolute selection and shrinkage operator (LASSO) and multivariate Cox regression analysis. We further investigated differences in survival rates and clinical characteristics among different risk groups. Furthermore, a nomogram was developed by combining riskscore with the clinical characteristics. We investigated the abundance of immune cells in the tumor microenvironment (TME) by CIBERSORT and single sample gene set enrichment analysis (ssGSEA) algorithms. Immunotherapy efficacy assessment was done with the assistance of Tumor Immune Dysfunction and Exclusion (TIDE) and The Cancer Immunome Atlas (TCIA) databases. Real-time quantitative polymerase chain reaction (RT-qPCR) experiments and immunohistochemical profiles of tissues were utilized to validate model genes. RESULTS: We identified 945 NKT cells marker genes from scRNA-seq data. Through further screening, 107 genes were accurately identified, of which 15 were significantly correlated with prognosis. We distinguished GBM samples into two distinct subtypes and successfully developed a robust prognostic prediction model. Survival analysis indicated that high expression of NKT cell marker genes was significantly associated with poor prognosis in GBM patients. Riskscore can be used as an independent prognostic factor. The nomogram was demonstrated remarkable utility in aiding clinical decision making. Tumor immune microenvironment analysis revealed significant differences of immune infiltration characteristics between different risk groups. In addition, the expression levels of immune checkpoint-associated genes were consistently elevated in the high-risk group, suggesting more prominent immune escape but also a stronger response to immune checkpoint inhibitors. CONCLUSIONS: By integrating scRNA-seq and bulk RNA-seq data analysis, we successfully developed a prognostic prediction model that incorporates two pivotal NKT cells marker genes, namely, CD44 and TNFSF14. This model has exhibited outstanding performance in assessing the prognosis of GBM patients. Furthermore, we conducted a preliminary investigation into the immune microenvironment across various risk groups that contributes to uncover promising immunotherapeutic targets specific to GBM.

Comprehensive analysis identifies cuproptosis-related gene DLAT as a potential prognostic and immunological biomarker in pancreatic adenocarcinoma.

BACKGROUND: Cuproptosis is a regulated cell death form associated with tumor progression, clinical outcomes, and immune response. However, the role of cuproptosis in pancreatic adenocarcinoma (PAAD) remains unclear. This study aims to investigate the implications of cuproptosis-related genes (CRGs) in PAAD by integrated bioinformatic methods and clinical validation. METHODS: Gene expression data and clinical information were downloaded from UCSC Xena platform. We analyzed the expression, mutation, methylation, and correlations of CRGs in PAAD. Then, based on the expression profiles of CRGs, patients were divided into 3 groups by consensus clustering algorithm. Dihydrolipoamide acetyltransferase (DLAT) was chosen for further exploration, including prognostic analysis, co-expression analysis, functional enrichment analysis, and immune landscape analysis. The DLAT-based risk model was established by Cox and LASSO regression analysis in the training cohort, and then verified in the validation cohort. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays were performed to examine the expression levels of DLAT in vitro and in vivo, respectively. RESULTS: Most CRGs were highly expressed in PAAD. Among these genes, increased DLAT could serve as an independent risk factor for survival. Co-expression network and functional enrichment analysis indicated that DLAT was engaged in multiple tumor-related pathways. Moreover, DLAT expression was positively correlated with diverse immunological characteristics, such as immune cell infiltration, cancer-immunity cycle, immunotherapy-predicted pathways, and inhibitory immune checkpoints. Submap analysis demonstrated that DLAT-high patients were more responsive to immunotherapeutic agents. Notably, the DLAT-based risk score model possessed high accuracy in predicting prognosis. Finally, the upregulated expression of DLAT was verified by RT-qPCR and IHC assays. CONCLUSIONS: We developed a DLAT-based model to predict patients' clinical outcomes and demonstrated that DLAT was a promising prognostic and immunological biomarker in PAAD, thereby providing a new possibility for tumor therapy.

miR-34a regulates macrophage-associated inflammation and angiogenesis in alcohol-induced liver injury.

BACKGROUND: Alcohol-associated liver disease (ALD) is a syndrome of progressive inflammatory liver injury and vascular remodeling associated with long-term heavy intake of ethanol. Elevated miR-34a expression, macrophage activation, and liver angiogenesis in ALD and their correlation with the degree of inflammation and fibrosis have been reported. The current study aims to characterize the functional role of miR-34a-regulated macrophage- associated angiogenesis during ALD. METHODS RESULTS: We identified that knockout of miR-34a in 5 weeks of ethanol-fed mice significantly decreased the total liver histopathology score and miR-34a expression, along with the inhibited liver inflammation and angiogenesis by reduced macrophage infiltration and CD31/VEGF-A expression. Treatment of murine macrophages (RAW 264.7) with lipopolysaccharide (20 ng/mL) for 24 h significantly increased miR-34a expression, along with the enhanced M1/M2 phenotype changes and reduced Sirt1 expression. Silencing of miR-34a significantly increased oxygen consumption rate (OCR) in ethanol treated macrophages, and decreased lipopolysaccharide-induced activation of M1 phenotypes in cultured macrophages by upregulation of Sirt1. Furthermore, the expressions of miR-34a and its target Sirt1, macrophage polarization, and angiogenic phenotypes were significantly altered in isolated macrophages from ethanol-fed mouse liver specimens compared to controls. TLR4/miR-34a knockout mice and miR-34a Morpho/AS treated mice displayed less sensitivity to alcohol-associated injury, along with the enhanced Sirt1 and M2 markers in isolated macrophages, as well as reduced angiogenesis and hepatic expressions of inflammation markers MPO, LY6G, CXCL1, and CXCL2. CONCLUSION: Our results show that miR-34a-mediated Sirt1 signaling in macrophages is essential for steatohepatitis and angiogenesis during alcohol-induced liver injury. These findings provide new insight into the function of microRNA-regulated liver inflammation and angiogenesis and the implications for reversing steatohepatitis with potential therapeutic benefits in human alcohol-associated liver diseases.

Hybrid Ligand Polymerization for Weakly Confined Lead Halide Perovskite Quantum Dots.

Rational ligand passivation is essential to achieve a higher performance of weakly confined lead halide perovskite quantum dots (PQDs) via a mechanism of surface chemistry and/or microstrain. In situ passivation with 3-mercaptopropyltrimethoxysilane (MPTMS) produces CsPbBr3 PQDs with an enhanced photoluminescence quantum yield (PLQY, ΦPL) of up to 99%; meanwhile, charge transport of the PQD film can be enhanced by one order of magnitude. Herein, we examine the effect of the molecular structure of MPTMS as the ligand exchange agent in comparison to octanethiol. Both thiol ligands promote crystal growth of PQDs, inhibit nonradiative recombination, and cause blue-shifted PL, while the silane moiety of MPTMS manipulates surface chemistry and outperforms owing to its unique cross-linking chemistry characterized by FTIR vibrations at 908 and 1641 cm-1. Emergence of the diagnostic vibrations is ascribed to hybrid ligand polymerization arising from the silyl tail group that confers the advantages of narrower size dispersion, lower shell thickness, more static surface binding, and higher moisture resistance. In contrast, the superior electrical property of the thiol-passivated PQDs is mostly determined by the covalent S-Pb bonding on the interface.

Dioscin induces osteosarcoma cell apoptosis by upregulating ROS-mediated P38 MAPK signaling.

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Many patients with osteosarcoma readily develop resistance to chemotherapy and have an extremely dismal prognosis. Dioscin, a saponin, is known to exhibit potent anticancer activities and induce cellular death of a variety of cancer types. However, the inhibitory effect of dioscin on osteosarcoma cells and its underlying mechanisms have not been fully elucidated. We investigated the responses of human U2-OS and MG63 osteosarcoma cells to dioscin with regard to proliferation, apoptosis, migration, and invasion, and studied the effect of dioscin on MAPK-related proteins by western blot analysis assays. Dioscin inhibited osteosarcoma cell proliferation, migration, and invasion. Moreover, it induced osteosarcoma cell apoptosis via reactive oxygen species (ROS)-dependent apoptotic signaling. N-acetylcysteine, a reactive oxygen species inhibitor, suppressed dioscin-induced apoptosis, indicating that ROS play an essential role in dioscin-induced apoptosis. Western blot analysis assays showed that p38 MAPK was upregulated after dioscin treatment, and that dioscin induced apoptosis by upregulating ROS-mediated p38 MAPK signaling. Our study suggests that dioscin possesses antitumor activities against human osteosarcoma cells, inhibits osteosarcoma cell proliferation, migration and invasion, and induces osteosarcoma cell apoptosis through upregulating ROS-mediated p38 MAPK signaling. This study may provide a new therapeutic strategy and potential clinical applications for the treatment of osteosarcoma.