Hounsfield unit for assessing bone mineral density distribution within lumbar vertebrae and its clinical values.

Study Design: Retrospective radiological analysis. Objective: The aim of this study is to evaluate the distribution of bone mineral density (BMD) in lumbar vertebrae using the Hounsfield unit (HU) measurement method and investigate the clinical implications of HU values for assessing lumbar vertebrae BMD. Method: Two hundred and ninety-six patients were retrospectively reviewed and divided into six groups according to age: Group 1(20-29 years old), Group 2 (30-39 years old), Group 3 (40-49 years old), Group 4 (50-59 years old), Group 5 (60-69 years old), Group 6 (70-79 years old). Six different locations from each vertebra of L1-L5 were selected as regions of interest: the anterior, middle and posterior parts of the upper and lower slices of the vertebrae. HU values were measured for the six regions of interest, followed by statistical analysis. Results: The HU values of vertebrae showed a decreasing trend from young patients to elderly patients in Group 1 to Group 5. There was no significant difference in HU values among different vertebrae in the same age group. In all age groups, the HU values of the anterior and posterior part of the vertebral body were significantly different from L1 to L3, with the anterior part of the vertebral body having lower HU values than the posterior part. The HU values of the anterior and posterior part of the vertebral body of L4 and L5 were statistically significant only in Group 5 and Group 6, and the HU values of the anterior part of the vertebral body were lower than those of the posterior part. The HU values of posterior part of L4 and L5 in Group6 were higher than those in Group5. Conclusion: Bone mineral density in the lumbar vertebrae is not uniformly distributed, potentially attributed to varying stress stimuli. The assessment of local HU values in the lumbar spine is of significant importance for surgical treatment.

Improving Microstructural Estimation in Time-Dependent Diffusion MRI With a Bayesian Method.

BACKGROUND: Accurately fitting diffusion-time-dependent diffusion MRI (td-dMRI) models poses challenges due to complex and nonlinear formulas, signal noise, and limited clinical data acquisition. PURPOSE: Introduce a Bayesian methodology to refine microstructural fitting within the IMPULSED (Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion) model and optimize the prior distribution within the Bayesian framework. STUDY TYPE: Retrospective. POPULATION: Involving 69 pediatric patients (median age 6 years, interquartile range [IQR] 3-9 years, 61% male) with 41 low-grade and 28 high-grade gliomas, of which 76.8% were identified within the brainstem or cerebellum. FIELD STRENGTH/SEQUENCE: 3 T, oscillating gradient spin-echo (OGSE) and pulsed gradient spin-echo (PGSE). ASSESSMENT: The Bayesian method's performance in fitting cell diameter ( d $$ d $$ ), intracellular volume fraction ( f in $$ {f}_{in} $$ ), and extracellular diffusion coefficient ( D ex $$ {D}_{ex} $$ ) was compared against the NLLS method, considering simulated and experimental data. The tumor region-of-interest (ROI) were manually delineated on the b0 images. The diagnostic performance in distinguishing high- and low-grade gliomas was assessed, and fitting accuracy was validated against H&E-stained pathology. STATISTICAL TESTS: T-test, receiver operating curve (ROC), area under the curve (AUC) and DeLong's test were conducted. Significance considered at P < 0.05. RESULTS: Bayesian methodology manifested increased accuracy with robust estimates in simulation (RMSE decreased by 29.6%, 40.9%, 13.6%, and STD decreased by 29.2%, 43.5%, and 24.0%, respectively for d $$ d $$ , f in $$ {f}_{in} $$ , and D ex $$ {D}_{ex} $$ compared to NLLS), indicating fewer outliers and reduced error. Diagnostic performance for tumor grade was similar in both methods, however, Bayesian method generated smoother microstructural maps (outliers ratio decreased by 45.3% ± 19.4%) and a marginal enhancement in correlation with H&E staining result (r = 0.721 for f in $$ {f}_{in} $$ compared to r = 0.698 using NLLS, P = 0.5764). DATA CONCLUSION: The proposed Bayesian method substantially enhances the accuracy and robustness of IMPULSED model estimation, suggesting its potential clinical utility in characterizing cellular microstructure. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis.

Background: The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated. Purpose: This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism. Methods: The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins. Results: The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin. Conclusion: Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.

Probiotic-derived amphiphilic exopolysaccharide self-assembling adjuvant delivery platform for enhancing immune responses.

Enhancing immune response activation through the synergy of effective antigen delivery and immune enhancement using natural, biodegradable materials with immune-adjuvant capabilities is challenging. Here, we present NAPSL.p that can activate the Toll-like receptor 4 (TLR4) pathway, an amphiphilic exopolysaccharide, as a potential self-assembly adjuvant delivery platform. Its molecular structure and unique properties exhibited remarkable self-assembly, forming a homogeneous nanovaccine with ovalbumin (OVA) as the model antigen. When used as an adjuvant, NAPSL.p significantly increased OVA uptake by dendritic cells. In vivo imaging revealed prolonged pharmacokinetics of NAPSL. p-delivered OVA compared to OVA alone. Notably, NAPSL.p induced elevated levels of specific serum IgG and isotype titers, enhancing rejection of B16-OVA melanoma xenografts in vaccinated mice. Additionally, NAPSL.p formulation improved therapeutic effects, inhibiting tumor growth, and increasing animal survival rates. The nanovaccine elicited CD4+ and CD8+ T cell-based immune responses, demonstrating the potential for melanoma prevention. Furthermore, NAPSL.p-based vaccination showed stronger protective effects against influenza compared to Al (OH)3 adjuvant. Our findings suggest NAPSL.p as a promising, natural self-adjuvanting delivery platform to enhance vaccine design across applications.

Thermal degradation of greenhouse gas SF6 at realistic temperatures: Insights from atomic-scale CVHD simulations.

Sulfur hexafluoride (SF6), recognized as a potent greenhouse gas with significant contributions to climate change, presents challenges in understanding its degradation processes. Molecular dynamics simulations are valuable tools for understanding modes of decomposition while the traditional approaches face limitations in time scale and require unrealistically high temperatures. The collective variable-driven hyperdynamics (CVHD) approach has been introduced to directly depict the pyrolysis process for SF6 gas at practical application temperatures, as low as 1600 K for the first time. Achieving an unprecedented acceleration factor of up to 107, the method extends the simulation time scale to milliseconds and beyond while maintaining consistency with experimental and theoretical models. The differences in the reaction process between simulations conducted at actual and elevated temperatures have been noted, providing insights into SF6 degradation pathways. The work provides a basis for the further studies on the thermal degradation of pollutants.

Proton pump inhibitors stabilize the expression of PD-L1 on cell membrane depending on the phosphorylation of GSK3ß.

BACKGROUND: Preclinical and clinical evidence indicates that proton pump inhibitors (PPIs) may indirectly diminish the microbiome diversity, thereby reducing the effectiveness of immune checkpoint inhibitors (ICIs). Conversely, recent publications have shown that PPIs could potentially enhance the response to ICIs. The precise mechanism through which PPIs modulate the ICIs remains unclear. In this study, we discovered a novel molecular function of PPIs in regulating immune invasion, specifically through inducing PD-L1 translocation in various tumor cells. METHODS: C57BL/6 mice subcutaneous transplantation model is used to verify the potential efficacy of PPIs and PD-L1 antibody. Western blotting analysis and phosphorylated chip are used to verify the alteration of PD-L1-related pathways after being treated with PPIs. The related gene expression is performed by qRT-PCR and luciferase reporter analysis. We also collected 60 clinical patients diagnosed with esophageal cancer or reflux esophagitis and then detected the expression of PD-L1 in the tissue samples by immunohistochemistry. RESULTS: We observed that the IC50 of tumor cells in response to PPIs was significantly higher than that of normal epithelial cells. PPIs significantly increased the expression of PD-L1 on cell membrane at clinically relevant concentrations. Furthermore, pre-treatment with PPIs appeared to synergize the efficiency of anti-PD-L1 antibodies in mouse models. However, PPI administration did not alter the transcription or total protein level of PD-L1 in multiple tumor cells. Using a phosphorylated protein chip, we identified that PPIs enhanced the phosphorylation of GSK3ß, then leading to PD-L1 protein translocation to the cell membranes. The capacity of PPIs to upregulate PD-L1 was negated following GSK3ß knockout. Furthermore, our clinical data showed that the PPIs use resulted in increased PD-L1 expression in esophageal cancer patients. CONCLUSION: We mainly address a significant and novel mechanism that the usage of PPIs could directly induce the expression of PD-L1 by inducing GSK3ß phosphorylation and facilitate primary tumor progression and metastasis.

Quaternary Ammonium Assisted Synthesis of Melanin-like Poly(l-DOPA) Nanoparticles with a Boosted Photothermal Effect.

Poly(levodopa) nanoparticles (P(l-DOPA) NPs) are another kind of melanin mimetic besides well-established polydopamine nanoparticles (PDA NPs). Due to the presence of carboxyl groups, the oxidative polymerization of l-DOPA to obtain particles was not as efficient as that of dopamine. Several established methods toward P(l-DOPA) NP fabrication do not combine convenience, morphological regularity, size controllability, low cost, and adaptability to metal-free application scenarios. In this work, P(l-DOPA) NPs were successfully prepared in hot water with the assistant of organic quaternary ammonium, due to the extra physical cross-linking mediated by cations. The employed physical interactions could also be affected by quaternary ammonium structure (i.e., number of cation heads, length of alkyl chain) to achieve different polymerization acceleration effects. The obtained P(l-DOPA) NPs retained superior photothermal properties and outperformed PDA-based melanin materials. Furthermore, P(l-DOPA) NPs were used in photothermal tumor therapy and showed better efficacy. This study offers new insights into the synthesis of melanin-like materials, as well as new understanding of the interaction between quaternary ammonium and bioinspired polyphenolic materials.

Expeditious Synthesis of Gwanakoside A and the Chloronaphthol Glycoside Congeners.

The synthesis of gwanakoside A, a chlorinated naphthol bis-glycoside, and its analogues was achieved through stepwise chlorination and donor-equivalent controlled regioselective phenol glycosylation with glycosyl N-phenyltrifluoroacetimidates as donors. Gwanakoside A displayed considerable inhibitory effects against various cancer cells and Staphylococcus aureus strains.

Epidemiology and genotypes analysis of human papillomavirus infection in Beijing, China.

BACKGROUND: This study aimed to investigate the epidemiology of high-risk human papillomavirus (HPV) in the female population in Beijing, China, and identify the relationship between HPV genotypes and host factors. METHODS: HPV testing was performed on women aged 15-89 (mean age 38.0 ± 10.9 years) from Beijing in 2020. High-risk HPV genotyping real-time polymerase chain reaction was used to determine HPV genotypes. The overall prevalence, age-specific prevalence, genotype distribution, and the correlation between HPV genotypes and cervical cytology were analyzed. RESULTS: Among the 25,344 study participants, the single and double infection rates were 18.8% (4,777/25,344) and 4.2% (1,072/25,344), respectively. A total of 6,119 HPV-positive individuals were found to have 91.6% negative results for intraepithelial lesion or malignancy (NILM), 5.8% atypical squamous cells of undetermined significance (ASC-US), 0.9% low-grade squamous intraepithelial lesion (LSIL), and 1.7% high-grade squamous intraepithelial lesion (HSIL). In single HPV infections, the HPV16 genotype was highly associated with cervical cytology severity (χ2 trend = 172.487, P < 0.001). Additionally, HPV infection rates increased gradually with age, and statistical differences were observed across age groups (χ2 = 180.575; P < 0.001). High-risk HPV genotypes were highly prevalent in women below 25 years of age and those aged 55-59 years. Cluster analysis revealed that the 13 HPV genotypes could be roughly divided into two groups in a single infection; however, patterns of infection consistent with biological characteristics were not observed. CONCLUSION: High-risk HPV was found in 24.1% of outpatients, with HPV52, HPV58, HPV16, HPV39, and HPV51 being the most common high-risk genotypes. Single high-risk HPV infection was predominant. HPV16, HPV39, HPV51, and HPV52 were associated with cervical lesion progression. HPV16 infection was especially worrying since it aggravates cervical lesions. Because the infection rates of the 13 HPV genotypes differed by age, the peak HPV infection rate should not guide vaccination, screening, and prevention programs. Instead, these initiatives should be tailored based on the regional HPV distribution characteristics. Moreover, it was determined that Beijing's populace needed to receive treatment for HPV39 infection.

Robust and Multifunctional Therapeutic Nanoparticles against Peritonitis-Induced Sepsis.

Apart from bacterial growth and endotoxin generation, the excessive production of reactive radicals linked with sepsis also has a substantial impact on triggering an inflammatory response and further treatment failure. Hence, the rational design and fabrication of robust and multifunctional nanoparticles (NPs) present a viable means of overcoming this dilemma. In this study, we used antibiotic polymyxin B (PMB) and antioxidant natural polyphenolic protocatechualdehyde (PCA) to construct robust and multifunctional NPs for sepsis treatment, leveraging the rich chemistries of PCA. The PMB release profile from the NPs demonstrated pH-responsive behavior, which allowed the NPs to exhibit effective bacterial killing and radical scavenging properties. Data from in vitro cells stimulated with H2O2 and lipopolysaccharide (LPS) showed the multifunctionalities of NPs, including intracellular reactive oxygen species (ROS) scavenging, elimination of the bacterial toxin LPS, inhibiting macrophage M1 polarization, and anti-inflammation capabilities. Additionally, in vivo studies further demonstrated that NPs could increase the effectiveness of sepsis treatment by lowering the bacterial survival ratio, the expression of the oxidative marker malondialdehyde (MDA), and the expression of inflammatory cytokine TNF-α. Overall, this work provides ideas of using those robust and multifunctional therapeutic NPs toward enhanced sepsis therapy efficiency.

Transcriptomics Provides Novel Insights into the Regulatory Mechanism of IncRNA HIF1 A-AS1 on Vascular Smooth Muscle Cells.

INTRODUCTION: Thoracic aortic aneurysm is a potentially fatal disease with a strong genetic contribution. The dysfunction of vascular smooth muscle cells (VSMCs) contributes to the formation of this aneurysm. Although previous studies suggested that long non-coding ribonucleic acid (RNA) hypoxia inducible factor 1 α-antisense RNA 1 (HIF1A-AS1) exerted a vital role in the progression and pathogenesis of thoracic aortic aneurysm, we managed to find a new regulatory mechanism of HIF1A-AS1 in VSMCs via transcriptomics. METHODS: Cell viability was detected by the cell counting kit-8 assay. Cell apoptosis was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide double staining. Transwell migration assay and wound healing assay were performed to check the migration ability of HIF1A-AS1 on VSMCs. The NextSeq XTen system (Illumina) was used to collect RNA sequencing data. Lastly, reverse transcription-quantitative polymerase chain reaction confirmed the veracity and reliability of RNA-sequencing results. RESULTS: We observed that overexpressing HIF1A-AS1 successfully promoted apoptosis, significantly altered cell cycle distribution, and greatly attenuated migration in VSMCs, further highlighting the robust promoting effects of HIF1A-AS1 to thoracic aortic aneurysm. Moreover, transcriptomics was implemented to uncover its underlying mechanism. A total of 175 differently expressed genes were identified, with some of them enriched in apoptosis, migration, and cell cycle-related pathways. Intriguingly, some differently expressed genes were noted in vascular development or coagulation function pathways. CONCLUSION: We suggest that HIF1A-AS1 mediated the progression of thoracic aortic aneurysm by not only regulating the function of VSMCs, but also altering vascular development or coagulation function.

Role of Circulating Tumor DNA in Colorectal Cancer.

Colorectal cancer (CRC) is a very common gastrointestinal tumor, ranking second in the global cause of cancer death. Because of the invasive nature of biopsy and cannot reflect the heterogeneity of tumor or monitor the dynamic progress of tumor, it is necessary to induce a novel noninvasive method to improve the current treatment strategies of colorectal cancer. Among all the components of liquid biopsy, circulating tumor DNA (ctDNA) may have the best future. CtDNA maintains the same genomic characteristics as those in matched tumor tissues, so it allows quantitative evaluation and analysis of mutation load in body fluid. Furthermore, because the half-life of ctDNA is from 16 min to several hours in circulation, the circulating ctDNA can be measured repeatedly within a certain period to monitor the response of CRC to treatment, the occurrence of drug resistance, and the diagnosis of recurrence.

Machine Learning Based on Computed Tomography Pulmonary Angiography in Evaluating Pulmonary Artery Pressure in Patients with Pulmonary Hypertension.

BACKGROUND: Right heart catheterization is the gold standard for evaluating hemodynamic parameters of pulmonary circulation, especially pulmonary artery pressure (PAP) for diagnosis of pulmonary hypertension (PH). However, the invasive and costly nature of RHC limits its widespread application in daily practice. PURPOSE: To develop a fully automatic framework for PAP assessment via machine learning based on computed tomography pulmonary angiography (CTPA). MATERIALS AND METHODS: A machine learning model was developed to automatically extract morphological features of pulmonary artery and the heart on CTPA cases collected between June 2017 and July 2021 based on a single center experience. Patients with PH received CTPA and RHC examinations within 1 week. The eight substructures of pulmonary artery and heart were automatically segmented through our proposed segmentation framework. Eighty percent of patients were used for the training data set and twenty percent for the independent testing data set. PAP parameters, including mPAP, sPAP, dPAP, and TPR, were defined as ground-truth. A regression model was built to predict PAP parameters and a classification model to separate patients through mPAP and sPAP with cut-off values of 40 mm Hg and 55 mm Hg in PH patients, respectively. The performances of the regression model and the classification model were evaluated by analyzing the intraclass correlation coefficient (ICC) and the area under the receiver operating characteristic curve (AUC). RESULTS: Study participants included 55 patients with PH (men 13; age 47.75 ± 14.87 years). The average dice score for segmentation increased from 87.3% ± 2.9 to 88.2% ± 2.9 through proposed segmentation framework. After features extraction, some of the AI automatic extractions (AAd, RVd, LAd, and RPAd) achieved good consistency with the manual measurements. The differences between them were not statistically significant (t = 1.222, p = 0.227; t = -0.347, p = 0.730; t = 0.484, p = 0.630; t = -0.320, p = 0.750, respectively). The Spearman test was used to find key features which are highly correlated with PAP parameters. Correlations between pulmonary artery pressure and CTPA features show a high correlation between mPAP and LAd, LVd, LAa (r = 0.333, p = 0.012; r = -0.400, p = 0.002; r = -0.208, p = 0.123; r = -0.470, p = 0.000; respectively). The ICC between the output of the regression model and the ground-truth from RHC of mPAP, sPAP, and dPAP were 0.934, 0.903, and 0.981, respectively. The AUC of the receiver operating characteristic curve of the classification model of mPAP and sPAP were 0.911 and 0.833. CONCLUSIONS: The proposed machine learning framework on CTPA enables accurate segmentation of pulmonary artery and heart and automatic assessment of the PAP parameters and has the ability to accurately distinguish different PH patients with mPAP and sPAP. Results of this study may provide additional risk stratification indicators in the future with non-invasive CTPA data.

Inversion-Recovery-Prepared Oscillating Gradient Sequence Improves Diffusion-Time Dependency Measurements in the Human Brain.

BACKGROUND: Oscillating gradient diffusion MRI (dMRI) enables measurements at a short diffusion-time (td ), but it is challenging for clinical systems. Particularly, the low b-value and low resolution may give rise to cerebrospinal fluid (CSF) contamination. PURPOSE: To assess the effect of CSF partial volume on td -dMRI measurements and efficacy of inversion-recovery (IR) prepared oscillating and pulsed gradient dMRI sequence to improve td -dMRI measurements in the human brain. STUDY TYPE: Prospective. SUBJECTS: Ten normal volunteers and six glioma patients. FIELD STRENGTH/SEQUENCE: A 3 T; three-dimensional (3D) IR-prepared oscillating gradient-prepared gradient spin-echo (GRASE) and two-dimensional (2D) IR-prepared oscillating gradient echo-planar imaging (EPI) sequences. ASSESSMENT: We assessed the td -dependent patterns of apparent diffusion coefficient (ADC) in several gray and white matter structures, including the hippocampal subfields (head, body, and tail), cortical gray matter, thalamus, and posterior white matter in normal volunteers. Pulsed gradient (0 Hz) and oscillating gradients at frequencies of 20 Hz, 40 Hz, and 60 Hz dMRI were acquired with GRASE and EPI sequences with or without the IR module. We also tested the td -dependency patterns in glioma patients using the EPI sequence with or without the IR module. STATISTICAL TESTS: The differences in ADC across the different td s were compared by one-way ANOVA followed by post hoc pairwise t-tests with Bonferroni correction. RESULTS: In the healthy subjects, brain regions that were possibly contaminated by CSF signals, such as the hippocampus (head, body, and tail) and cortical gray matter, td -dependent ADC changes were only significant with the IR-prepared 2D and 3D sequences but not with the non-IR sequences. In brain glioblastomas patients, significantly higher td -dependence was observed in the tumor region with the IR module than that without IR (slope = 0.0196 µm2 /msec2 vs. 0.0034 µm2 /msec2 ). CONCLUSION: The IR-prepared sequence effectively suppressed the CSF partial volume effect and significantly improved the td -dependent measurements in the human brain. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Transcriptomics Provides Novel Insights into the Regulatory Mechanism of IncRNA HIF1 A-AS1 on Vascular Smooth Muscle Cells

ABSTRACT Introduction: Thoracic aortic aneurysm is a potentially fatal disease with a strong genetic contribution. The dysfunction of vascular smooth muscle cells (VSMCs) contributes to the formation of this aneurysm. Although previous studies suggested that long non-coding ribonucleic acid (RNA) hypoxia inducible factor 1 α-antisense RNA 1 (HIF1A-AS1) exerted a vital role in the progression and pathogenesis of thoracic aortic aneurysm, we managed to find a new regulatory mechanism of HIF1A-AS1 in VSMCs via transcriptomics. Methods: Cell viability was detected by the cell counting kit-8 assay. Cell apoptosis was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide double staining. Transwell migration assay and wound healing assay were performed to check the migration ability of HIF1A-AS1 on VSMCs. The NextSeq XTen system (Illumina) was used to collect RNA sequencing data. Lastly, reverse transcription-quantitative polymerase chain reaction confirmed the veracity and reliability of RNA-sequencing results. Results: We observed that overexpressing HIF1A-AS1 successfully promoted apoptosis, significantly altered cell cycle distribution, and greatly attenuated migration in VSMCs, further highlighting the robust promoting effects of HIF1A-AS1 to thoracic aortic aneurysm. Moreover, transcriptomics was implemented to uncover its underlying mechanism. A total of 175 differently expressed genes were identified, with some of them enriched in apoptosis, migration, and cell cycle-related pathways. Intriguingly, some differently expressed genes were noted in vascular development or coagulation function pathways. Conclusion: We suggest that HIF1A-AS1 mediated the progression of thoracic aortic aneurysm by not only regulating the function of VSMCs, but also altering vascular development or coagulation function.

Jatrorrhizine Alleviates DSS-Induced Ulcerative Colitis by Regulating the Intestinal Barrier Function and Inhibiting TLR4/MyD88/NF-κB Signaling Pathway.

Background: Ulcerative colitis (UC), a kind of autoimmune disease with unknown etiology, has been troubling human physical and mental health. Jatrorrhizine (Jat) is a natural isoquinoline alkaloid isolated from Coptis Chinensis, which has been proved to have antibacterial, anti-inflammatory, and antitumor effects. Purpose: The purpose is to explore the therapeutic effect of Jat on DSS-induced UC and the mechanism of action. Study Design. The UC mice model was induced by 3% DSS in drinking water. The mice were orally administered with Jat (40, 80, 160 mg/kg) for 10 days. Methods: The changes in body weight, colon length, spleen wet weight index, disease activity index (DAI), colonic histopathology, and inflammatory factors of serum and colon tissue were analyzed to evaluate the severity of colitis mice. The colon mucus secretion capacity was analyzed by Alcian blue periodic acid Schiff (AB-PAS) staining. Furthermore, protein expressions such as TLR4, MyD88, p-NF-κB-p65, NF-κB-p65, COX-2, ZO-1, and Occludin were detected to elucidate the molecular mechanism of Jat on DSS-induced colitis model. Results: The results showed that Jat could significantly alleviate the symptoms, colon shortening, spleen index, and histological damage and restore the body weight in DSS-induced colitis mice. Jat also suppressed the levels of inflammatory cytokines and upregulated the levels of anti-inflammatory cytokines. In addition, Jat repaired the intestinal barrier function by upregulating the level of colonic tight junction (TJ) proteins and enhancing the secretion of mucin produced by goblet cells. Furthermore, Jat could significantly suppress the expression of TLR4, MyD88, p-NF-κB-p65/NF-κB-p65, and COX-2 in colon tissue. Conclusion: The results suggested that Jat plays a protective role in DSS-induced colitis by regulating the intestinal barrier function and inhibiting the TLR4/MyD88/NF-κB signaling pathway. This study, for the first time, demonstrates the therapeutic and protective effects of Jat on UC.

The multifunctional Prussian blue/graphitic carbon nitride nanocomposites for fluorescence imaging-guided photothermal and photodynamic combination therapy.

Cancer has been regarded as one of the most intractable diseases worldwide and threatens human health and life. Photothermal/Photodynamic therapy (PTT and PDT) have emerged as reliable and effective strategies in cancer treatment with the superiorities of non-invasiveness, slight side effects, and high treatment efficiency. Herein, a nanocomposite (PBCN) was fabricated via electrostatic interaction between Prussian blue nanoparticles (PBNPs) and graphitic carbon nitride (g-C3N4), and the resulting PBCN possessed good photothermal properties and excellent photodynamic effects with 808 nm irradiation. Furthermore, it exhibits excellent fluorescence imaging ability in cells, highlighting its potential as a powerful imaging agent in the biomedical field. Combination with a photothermal material, photosensitizer, and fluorescence imaging agent would thus allow PBCN to realize fluorescence imaging-guided PTT/PDT, showing an outstanding theranostic effect on cancer cells.

GATA4 regulates osteogenic differentiation by targeting miR-144-3p.

Numerous studies have demonstrated that microRNAs (miRNAs or miRs) play an important role in regulating osteogenic differentiation, but their specific regulatory mechanism requires further investigation. In the present study, it was revealed that during osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs), the expression level of miR-144-3p was decreased with increased osteogenic induction duration and was negatively associated with osteogenic marker gene expression. Overexpression of miR-144-3p inhibited osteogenic differentiation, while inhibition of miR-144-3p expression promoted osteogenic differentiation. In addition, dual-luciferase activity analysis and adenovirus infection experiments revealed that GATA binding protein 4 targeted miR-144-3p for regulation and that overexpression of GATA4 promoted the expression of miR-144-3p. These data indicated that miR-144-3p plays a role in inhibiting BMSC osteogenic differentiation and that GATA4 inhibits osteogenic differentiation by targeting miR-144-3p expression.

Facile access to C-glycosyl amino acids and peptides via Ni-catalyzed reductive hydroglycosylation of alkynes.

C-Glycosyl peptides/proteins are metabolically stable mimics of the native glycopeptides/proteins bearing O/N-glycosidic linkages, and are thus of great therapeutical potential. Herein, we disclose a protocol for the syntheses of vinyl C-glycosyl amino acids and peptides, employing a nickel-catalyzed reductive hydroglycosylation reaction of alkyne derivatives of amino acids and peptides with common glycosyl bromides. It accommodates a wide scope of the coupling partners, including complex oligosaccharide and peptide substrates. The resultant vinyl C-glycosyl amino acids and peptides, which bear common O/N-protecting groups, are amenable to further transformations, including elongation of the peptide and saccharide chains.

Clinical efficacy and safety of Tanreqing injection combined with antibiotics versus antibiotics alone in the treatment of pulmonary infection patients after chemotherapy with lung cancer: A systematic review and meta-analysis.

This study aimed to evaluate the efficacy and safety of Tanreqing injection (TRQi) in the treatment of pulmonary infection after chemotherapy in patients with lung cancer. Cochrane Library, PubMed, Web of Science, EMbase, CNKI, VMIS, Wan-Fang, and CBM databases were comprehensively searched from established to March 2020. randomized controlled trials (RCTs) of TRQi were selected. The evaluation manual of Cochrane RCT was used to evaluate the methodological quality of all included studies, Stata 13.0 and Review Manager 5.3 software was used for meta-analysis. This study is registered with PROSPERO (CRD42020175533). Eighteen RCTs with a total of 1,438 patients were met the inclusion criteria. Meta-analysis showed that compared with antibiotics alone, TRQi plus antibiotics could significantly improve the clinical efficacy, defervescence time, lung rale disappearance time, cough disappearance time, and average hospitalization time, reduce white blood cell, C-reactive protein, and procalcitonin levels, and adverse reactions. However, due to the small sample size and low quality of the study, more rigorous and more RCTs are needed for further verification. In conclusion, this study provides useful evidence for the efficacy and safety of TRQi combined with antibiotics in the treatment of pulmonary infection after chemotherapy with lung cancer.