Coronary inflammation based on pericoronary adipose tissue attenuation in type 2 diabetic mellitus: effect of diabetes management.

BACKGROUND: Coronary inflammation plays crucial role in type 2 diabetes mellitus (T2DM) induced cardiovascular complications. Both glucose-lowering drug interventions (GLDIS) and glycemic control (GC) status potentially correlate coronary inflammation, as indicated by changes in pericoronary adipose tissue (PCAT) attenuation, and thus influence cardiovascular risk. This study evaluated the impact of GLDIS and GC status on PCAT attenuation in T2DM patients. METHODS: This retrospective study collected clinical data and coronary computed tomography angiography (CCTA) images of 1,342 patients, including 547 T2DM patients and 795 non-T2DM patients in two tertiary hospitals. T2DM patients were subgroup based on two criteria: (1) GC status: well: HbA1c < 7%, moderate: 7 ≤ HbA1c ≤ 9%, and poor: HbA1c > 9%; (2) GLDIS and non-GLDIS. PCAT attenuations of the left anterior descending artery (LAD-PCAT), left circumflex artery (LCX-PCAT), and right coronary artery (RCA-PCAT) were measured. Propensity matching (PSM) was used to cross compare PCAT attenuation of non-T2DM and all subgroups of T2DM patients. Linear regressions were conducted to evaluate the impact of GC status and GLDIS on PCAT attenuation in T2DM patients. RESULTS: Significant differences were observed in RCA-PCAT and LCX-PCAT between poor GC-T2DM and non-T2DM patients (LCX: - 68.75 ± 7.59 HU vs. - 71.93 ± 7.25 HU, p = 0.008; RCA: - 74.37 ± 8.44 HU vs. - 77.2 ± 7.42 HU, p = 0.026). Higher PCAT attenuation was observed in LAD-PCAT, LCX-PCAT, and RCA-PCAT in non-GLDIS T2DM patients compared with GLDIS T2DM patients (LAD: - 78.11 ± 8.01 HU vs. - 75.04 ± 8.26 HU, p = 0.022; LCX: - 71.10 ± 8.13 HU vs. - 68.31 ± 7.90 HU, p = 0.037; RCA: - 78.17 ± 8.64 HU vs. - 73.35 ± 9.32 HU, p = 0.001). In the linear regression, other than sex and duration of diabetes, both metformin and acarbose were found to be significantly associated with lower LAD-PCAT (metformin: ß coefficient = - 2.476, p=0.021; acarbose: ß coefficient = - 1.841, p = 0.031). CONCLUSION: Inadequate diabetes management, including poor GC and lack of GLDIS, may be associated with increased coronary artery inflammation in T2DM patients, as indicated by PCAT attenuation on CCTA, leading to increased cardiovascular risk. This finding could help healthcare providers identify T2DM patients with increased cardiovascular risk, develop improved cardiovascular management programs, and reduce subsequent cardiovascular related mortality.

Analysis of fecal microbiome and metabolome changes in goats with pregnant toxemia.

BACKGROUND: Pregnancy toxemia is a common disease, which occurs in older does that are pregnant with multiple lambs in the third trimester. Most of the sick goats die within a few days, which can seriously impact the economic benefits of goat breeding enterprises. The disease is believed to be caused by malnutrition, stress, and other factors, that lead to the disorder of lipid metabolism, resulting in increased ketone content, ketosis, ketonuria, and neurological symptoms. However, the changes in gut microbes and their metabolism in this disease are still unclear. The objective of this experiment was to evaluate the effect of toxemia of pregnancy on the fecal microbiome and metabolomics of does. RESULTS: Eight pregnant does suspected of having toxemia of pregnancy (PT group) and eight healthy does during the same pregnancy (NC group) were selected. Clinical symptoms and pathological changes at necropsy were observed, and liver tissue samples were collected for pathological sections. Jugular venous blood was collected before morning feeding to detect biochemical indexes. Autopsy revealed that the liver of the pregnancy toxemia goat was enlarged and earthy yellow, and the biochemical results showed that the serum levels of aspartate aminotransferase (AST) and ß-hydroxybutyric acid (B-HB) in the PT group were significantly increased, while calcium (Ca) levels were significantly reduced. Sections showed extensive vacuoles in liver tissue sections. The microbiome analysis found that the richness and diversity of the PT microbiota were significantly reduced. Metabolomic analysis showed that 125 differential metabolites were screened in positive ion mode and enriched in 12 metabolic pathways. In negative ion mode, 100 differential metabolites were screened and enriched in 7 metabolic pathways. CONCLUSIONS: Evidence has shown that the occurrence of pregnancy toxemia is related to gut microbiota, and further studies are needed to investigate its pathogenesis and provide research basis for future preventive measures of this disease.

Emodin suppresses adipogenesis of bone marrow derived mesenchymal stem cells from aplastic anemia via increasing TRIB3 expression.

BACKGROUND: Increasing evidence indicate that enhanced adipogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) could contribute to the adiposity alteration in marrow microenvironment of aplastic anemia (AA). Identifying small molecule drugs with role in inhibiting adipogenesis of BM-MSCs may represent a novel direction in AA therapy by improving BM-MSCs mediated marrow microenvironment. METHODS: For the purpose, we isolated AA BM-MSCs through whole bone marrow cell culture, evaluated a series of small molecule drugs using the in vitro adipogenic differentiation model of BM-MSCs, and finally focused on emodin, a natural anthraquinone derivative. Subsequently, we systematically investigated the molecular mechanism of emodin in attenuating adipogenic process by means of microarray profiling, bioinformatics analysis and lentivirus-mediated functional studies and rescue assay. RESULTS: We found that emodin presented significantly suppressive effect on the in vitro adipogenic differentiation of AA BM-MSCs. Further mechanistic investigation revealed that emodin could increase the expression of Tribbles homolog 3 (TRIB3) which exhibited remarkably decreased expression in AA BM-MSCs compared with the normal counterparts and was subsequently demonstrated as a negative regulator in adipogenesis of AA BM-MSCs. Besides, TRIB3 depletion alleviated the suppressive effect of emodin on the adipogenic differentiation of AA BM-MSCs. CONCLUSION: Our findings propose that emodin mediated TRIB3 up-regulation alleviates the adipogenic capacity of AA BM-MSCs, and emodin could serve as a potential therapeutic regimen for AA therapy.

Lower limb arterial calcification and its clinical relevance with peripheral arterial disease.

Lower limb arterial calcification (LLAC) is associated with an increased risk of mortality and it predicts poor outcomes after endovascular interventions in patients with peripheral artery disease (PAD). Detailed histological analysis of human lower artery specimens pinpointed the presence of LLAC in two distinct layers: the intima and the media. Intimal calcification has been assumed to be an atherosclerotic pathology and it is associated with smoking and obesity. It becomes instrumental in lumen stenosis, thereby playing a crucial role in disease progression. On the contrary, medial calcification is a separate process, systematically regulated and linked with age advancement, diabetes, and chronic kidney disease. It prominently interacts with vasodilation and arterial stiffness. Given that both types of calcifications frequently co-exist in PAD patients, it is vital to understand their respective mechanisms within the context of PAD. Calcification can be easily identifiable entity on imaging scans. Considering the highly improved abilities of novel imaging technologies in differentiating intimal and medial calcification within the lower limb arteries, this review aimed to describe the distinct histological and imaging features of the two types of LLAC. Additionally, it aims to provide in-depth insight into the risk factors, the effects on hemodynamics, and the clinical implications of LLAC, either occurring in the intimal or medial layers.

Circumferential degree of tibial artery calcification is associated with infrapopliteal endovascular revascularization outcomes in patients with chronic limb-threatening ischemia.

BACKGROUND: Tibial artery calcification (TAC) is correlated with an increased risk of amputation and mortality in patients with chronic limb-threatening ischemia (CLTI). The association between calcification characteristics and adverse limb events of CLTI. However, it has not been assessed. This study aims to assess the relationship between the characteristics of TAC based on computed tomography angiography (CTA) scans and postoperative outcomes in patients with CLTI undergoing infrapopliteal endovascular therapy. METHODS: This was a retrospective study of patients who underwent infrapopliteal endovascular revascularization for CLTI and had a preoperative CTA scan. Based on CTA, TAC was divided into the following categories: annularity, thickness, continuity and severity. Cox regression models using generalized estimating equations were performed to assess the relationship between calcification characteristics and postoperative outcomes. The outcomes evaluated were the occurrence of all cause mortality (ACM) and unplanned amputation. RESULTS: Among the 148 patients undergoing endovascular, there were 50 (33.8%) patients died and 26 (17.6%) patients underwent unplanned amputation. Annular calcification was more common in the ACM group than in the non-ACM group. No significant differences were found between the two groups with regard to the probability of calcification in the thickness and the continuity (P>0.05). Patients in the unplanned amputation group had significantly annular, thin and continuity calcifications (P<0.05) than those in the non-unplanned amputation group. The presence of annular calcification was an independent predictor of ACM (hazard ratio (HR), 3.186; 95% confidence interval (CI), 1.781-5.702; P<0.001) and unplanned amputation (HR, 3.739; 95% CI, 1.707-8.191; P<0.05). CONCLUSIONS: Among patients with CLTI, the occurrence of annular calcification in the tibial artery are related to a greater chance of ACM and unplanned amputation in the postoperative period. The circumferential degree of TAC of the operated limb can be considered as a marker of clinical prognosis in this group of patients.

Apicidin confers promising therapeutic effect on acute myeloid leukemia cells via increasing QPCT expression.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by abnormal cell proliferation, apoptosis repression and myeloid differentiation blockade of hematopoietic stem/progenitor cells. Developing and identifying novel therapeutic agents to reverse the pathological processes of AML are of great significance. Here in this study, we found that a fungus-derived histone deacetylase inhibitor, Apicidin, presents promising therapeutic effect on AML by inhibiting cell proliferation, facilitating apoptosis and inducing myeloid differentiation of AML cells. Mechanistic investigation revealed that QPCT is identified as a potential downstream target of Apicidin, which exhibits significantly decreased expression in AML samples compared with the normal controls and is remarkably up-regulated in AML cells upon Apicidin management. Functional study and rescue assay demonstrated that QPCT depletion further promotes cell proliferation, inhibits apoptosis and impairs myeloid differentiation of AML cells, alleviating the anti-leukemic effect of Apicidin on AML. Our findings not only provide novel therapeutic target for AML, but also lay theoretical and experimental foundation for the clinical application of Apicidin in AML patients.

Chidamide suppresses adipogenic differentiation of bone marrow derived mesenchymal stem cells via increasing REEP2 expression.

Increased propensity of bone marrow-derived mesenchymal stem cells (BM-MSCs) toward adipogenic differentiation at the expense of osteogenesis has been implicated in obesity, diabetes, and age-related osteoporosis as well as various hematopoietic disorders. Defining small molecules with role in rectifying the adipo-osteogenic differentiation imbalance is of great significance. Here, we unexpectedly found that Chidamide, a selective histone deacetylases inhibitor, exhibited remarkably suppressive effect on the in vitro induced adipogenic differentiation of BM-MSCs. Multifaceted alterations in the spectrum of gene expression were observed in Chidamide-managed BM-MSCs during adipogenic induction. Finally, we focused on REEP2, which presented decreased expression in BM-MSCs-mediated adipogenesis and was restored by Chidamide treatment. REEP2 was subsequently demonstrated as a negative regulator of adipogenic differentiation of BM-MSCs and mediated the suppressive effect of Chidamide on adipocyte development. Our findings provide the theoretical and experimental foundation for the clinical application of Chidamide for disorders associated with excessive marrow adipocytes.

Hypertension Exacerbates Severity and Outcomes of COVID-19 in Elderly Patients: A Retrospective Observational Study.

OBJECTIVE: To evaluate the impact of hypertension on the clinical outcome of COVID-19 patients aged 60 years old and older. METHODS: This single-center retrospective cohort study enrolled consecutive COVID-19 patients aged 60 years old and older, who were admitted to Liyuan Hospital from January 1, 2020 to April 25, 2020. All included patients were divided into two groups: hypertension and nonhypertension group. The baseline demographic characteristics, laboratory test results, chest computed tomography (CT) images and clinical outcomes were collected and analyzed. The prognostic value of hypertension was determined using binary logistic regression. RESULTS: Among the 232 patients included in the analysis, 105 (45.3%) patients had comorbid hypertension. Compared to the nonhypertension group, patients in the hypertension group had higher neutrophil-to-lymphocyte ratios, red cell distribution widths, lactate dehydrogenase, high-sensitivity C-reactive protein, D-dimer and severity of lung lesion, and lower lymphocyte counts (all P<0.05). Furthermore, the hypertension group had a higher proportion of intensive care unit admissions [24 (22.9%) vs. 14 (11.0%), P=0.02) and deaths [16 (15.2%) vs. 3 (2.4%), P<0.001] and a significantly lower probability of survival (P<0.001) than the nonhypertension group. Hypertension (OR: 4.540, 95% CI: 1.203-17.129, P=0.026) was independently correlated with all-cause in-hospital death in elderly patients with COVID-19. CONCLUSION: The elderly COVID-19 patients with hypertension tend to have worse conditions at baseline than those without hypertension. Hypertension may be an independent prognostic factor of poor clinical outcome in elderly COVID-19 patients.

Performance evaluation of the emerging rural sewage treatment facilities in China.

Urban water pollution has been well controlled by strict management in the past few decades in China. Thus, the central government started to place emphasis on rural water pollution, and increasing number of sewage treatment facilities have been constructed, and currently, they are operating in China. Therefore, thoroughly assessing the operating conditions and the performance of these facilities is important. This article analyzes life cycle assessment and life cycle cost to evaluate the environmental and economic performance of four common technologies to determine how the emerging rural sewage treatment facilities in China are running. The results showed that the plant-adopted anaerobic-anoxic-oxic process was an optimal scheme for lower environmental impact that was also cost-effective. All technologies had similar impacts on eleven environmental categories. Due to cement consumption during the construction phase and electricity consumption during the operation phase, the marine aquatic ecotoxicity potential was the greatest contributor, accounting for approximately 90% of the total potential impact. In addition, this research revealed that electricity consumption during the operation phase was responsible for almost all environmental impact categories, except for eutrophication potential and ozone layer depletion potential categories. Lastly, scenario analysis indicated that reusing treated water and adjusting power structure could be useful measures to promote the sustainable development of rural water environments.

Corilagin induces apoptosis and inhibits autophagy of HL­60 cells by regulating miR­451/HMGB1 axis.

Corilagin is the primary active component of the Euphorbia phyllanthus plant and has significant anti­cancer properties. However, the biological effects and mechanisms of corilagin on acute myeloid leukemia (AML) have not been clarified. The Cell Counting Kit­8 and Carboxyfluorescein Diacetate Succinimidyl Ester assay results showed that corilagin significantly inhibited proliferation of the AML cell line HL­60 in a time­ and dose­dependent manner. Western blotting and flow cytometry analysis were performed to determine the levels of apoptosis in HL­60 cells. The protein levels of cleaved caspase­3 and Bak were upregulated, while Bcl­xl was downregulated in cells treated with corilagin. The percentage of early­ and late­stage apoptotic cells increased following corilagin treatment in a dose­dependent manner, indicating that the intrinsic mitochondrial apoptosis pathway was activated by corilagin. Simultaneously, western blotting and immunofluorescence results revealed that autophagy was suppressed; this was accompanied by a decrease in light chain 3­II (LC3­II) conversion and autophagosomes. MicroRNA (miRNA/miR) profile analysis showed that corilagin elevated the expression of the tumor suppressor miR­451, while the mRNA and protein levels of high mobility group protein B1 (HMGB1), the target of miR­451, decreased following exposure to corilagin. Knockdown of miR­451 decreased the downregulation of HMGB1 caused by corilagin, indicating negative regulation of HMGB1 by miR­451 during corilagin treatment. Furthermore, knockdown of miR­451 also attenuated corilagin­induced proliferation inhibition of HL­60 cells, implying that miR­451 was essential for the proliferation inhibitory effect of corilagin. In conclusion, these results indicated that corilagin induced apoptosis and inhibited autophagy in HL­60 cells by regulating the miR­451/HMGB1 axis, and corilagin may be a novel therapeutic drug for the treatment of AML.

Aberrant Functional Connectivity of the Posterior Cingulate Cortex in Type 2 Diabetes Without Cognitive Impairment and Microvascular Complications.

Objective: We aimed to investigate the alterations of brain functional connectivity (FC) in type 2 diabetes mellitus (T2DM) patients without clinical evidence of cognitive impairment and microvascular complications (woCIMC-T2DM) using resting-state functional MRI (rs-fMRI) and to determine whether its value was correlated with clinical indicators. Methods: A total of 27 T2DM and 26 healthy controls (HCs) were prospectively examined. Cognitive impairment was excluded using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scales, and microvascular complications were excluded by fundus photography, microalbuminuria, and other indicators. The correlation maps, derived from rs-fMRI with posterior cingulate cortex (PCC) as the seed, were compared between T2DM patients and HCs. Pearson's correlation analysis was performed to determine the relationship between the FC of PCC and the clinical indicators. Results: Compared with HC, woCIMC-T2DM patients showed significantly decreased FCs with PCC (PCC-FCs) in the anterior cingulate cortex (ACC), right superior frontal gyrus, right medial frontal gyrus, and right angular gyrus. Meanwhile, increased PCC-FCs was observed in the right superior temporal gyrus and calcarine fissure (CAL). The FC of PCC-ACC was negatively correlated with glycosylated hemoglobin (HbA1c) and diabetes duration, and the FC of PCC-CAL was significantly positively correlated with HbA1c and diabetes duration. Conclusion: The FC, especially of the PCC with cognitive and visual brain regions, was altered before clinically measurable cognitive impairment and microvascular complications occurred in T2DM patients. In addition, the FC of the PCC with cognitive and visual brain regions was correlated with HbA1c and diabetes duration. This indicates that clinicians should pay attention not only to blood glucose control but also to brain function changes before the occurrence of adverse complications, which is of great significance for the prevention of cognitive dysfunction and visual impairment.

How are typical urban sewage treatment technologies going in China: from the perspective of life cycle environmental and economic coupled assessment.

Sewage treatment is an important public service, but it consumes a lot of energy and chemicals in the process of removing wastewater pollutants, which may cause the risk of pollution transfer. To find the corresponding hot issues, this paper took the lead in integrating life cycle assessment (LCA) with life cycle costing (LCC) to evaluate four most typical sewage treatment technologies with more than 85% share in China. It is found that anaerobic/anoxic/oxic (AAO) was the optimal treatment scheme with relatively small potential environmental impact and economic load. The normalized results show that the trends of the four technologies on eleven environmental impact categories were basically the same. Marine aquatic ecotoxicity potential accounted for more than 70% of the overall environmental impact. Contribution analysis indicates that electricity and flocculant consumption were the main processes responsible for the environmental and economic burden. Overall, electricity consumption was the biggest hot spot. Sensitivity analysis verifies that a 10% reduction in electricity could bring high benefits to both the economy and the environment. These findings are expected to provide effective feedback on the operation and improvement of sewage treatment. Graphical abstract.

Corilagin induces human glioblastoma U251 cell apoptosis by impeding activity of (immuno)proteasome.

Glioma is a type of common primary intracranial tumor, which is difficult to treat. It has been confirmed by research that corilagin (the primary active constituent of the matsumura leafflower herb) has significant antitumor effect. In particular, our previous research demonstrated that corilagin effectively promotes apoptosis of glioma U251 cells and has a synergistic effect when used with temozolomide. However, the mechanism by which corilagin causes apoptosis in U251 cells has yet to be investigated. Proteasomes are catalytic centers of the ubiquitin­proteasome system, which is the major protein degradation pathway in eukaryotic cells; they are primarily responsible for the degradation of signal molecules, tumor suppressors, cyclins and apoptosis inhibitors and serve an important role in tumor cell proliferation and apoptosis. The present study investigated the pro­apoptotic effect of corilagin on glioma U251 cells and confirmed that decreased proteasome activity and expression levels serve an important role in corilagin­induced U251 cell apoptosis.

Deep learning-based classification of lower extremity arterial stenosis in computed tomography angiography.

PURPOSE: The purpose of this study is to develop and evaluate a deep learning model to assist radiologists in classifying lower extremity arteries based on the degree of arterial stenosis caused by plaque in lower extremity computed tomography angiography (CTA) of patients with peripheral artery disease. METHODS: In this retrospective study, 265 patients who underwent lower-extremity CTA between January 1, 2016 and October 31, 2019 were selected. A total of 17050 axial images of iliac, femoropopliteal and infrapopliteal artery from these patients were used for the training and validation of the parallel efficient network (p-EffNet), a kind of supervised convolutional neural network, to classify the lower-extremity artery segments according to the degree of stenosis with digital subtraction angiography as reference standard. The classification results of the p-EffNet were then compared with those obtained from radiologists. Receiver operating characteristic curve (ROC) was used to evaluate the performance of the p-EffNet and accuracy, specificity, sensitivity and area under the curve (AUC) were used as measure metrics to compare the performance of the p-EffNet and that of radiologists. RESULTS: The p-EffNet exhibited a good performance of 91.5 % accuracy, 0.987 AUC and 90.2 % sensitivity and 97.7 % specificity in classifying above-knee artery and 90.9 % accuracy, 0.981 AUC, 91.3 % sensitivity and 95.2 % specificity in classifying below-knee artery. When compared with human readers, for both above-knee and below-knee artery, the p-EffNet had comparable accuracy (p = 0.266 and p = 0.808, respectively) and specificity (p = 0.118 and p = 0.971, respectively) but lower sensitivity (p < 0.001 and p = 0.022, respectively). CONCLUSIONS: The p-EffNet demonstrates promising diagnostic performance and has the potential to reduce the workload of radiologists and help to find the plaques that might otherwise have been missed or misjudged.

HMGB1: an important regulator of myeloid differentiation and acute myeloid leukemia as well as a promising therapeutic target.

High mobility group box 1 (HMGB1) is a non-histone nuclear protein which has been intensively studied in various physiological and pathological processes including leukemia. Here in this study, we further demonstrated that HMGB1 presents higher expression in the bone marrow mononuclear cells of acute myeloid leukemia (AML) patients compared with the normal controls and contributes to the AML pathogenesis and progression by inhibiting apoptosis, facilitating proliferation, and inducing myeloid differentiation blockade of AML cells. Mechanistic investigation revealed that transforming growth factor beta-induced (TGFBI) acts as a potential downstream target of HMGB1 and lentivirus-mediated knockdown of TGFBI expression impaired phorbol-12-myristate-13-acetate (PMA) and all-trans retinoic acid (ATRA)-induced myeloid differentiation of AML cell lines. On the other hand, chidamide, an orally histone deacetylase inhibitor, decreases HMGB1 expression significantly in AML cells with concomitant upregulation of TGFBI expression, and confers therapeutic effect on AML by inducing cell differentiation, apoptosis and inhibiting cell proliferation. In conclusion, our findings provide additional insights that HMGB1 is a promising therapeutic target of AML, and also present experimental evidence for the clinical application of chidamide as a novel agent in AML therapy by downregulating HMGB1 expression. KEY MESSAGES: HMGB1 induces cell proliferation and myeloid differentiation blockade and inhibits apoptosis of AML cells. TGFBI acts as a potential target of HMGB1. Chidamide, a selective HDAC inhibitor, confers promising therapeutic effect for AML via downregulating HMGB1 expression.

Intravenous immunoglobulin promotes the proliferation of CD4+CD25+ Foxp3+ regulatory T cells and the cytokines secretion in patients with Guillain-Barré syndrome in vitro.

Intravenous immunoglobulin (IVIg) serves as the first line therapy in Guillain-Barré syndrome (GBS), however, its action mechanism remains unknown. We hereby stimulated peripheral blood mononuclear cells (PBMCs) from patients with GBS and healthy controls using IVIg and an IgG-derived natural Treg epitopes, namely Tregitopes. Our results showed that IVIg significantly promoted both the expansion of CD4+CD25+Foxp3+ regulatory T cells (Tregs) and secretion of IL-10 and TGF-ß1 while Tregitopes promoted secretion of IL-10 and TGF-ß1 only. Further study is necessary to elucidate the molecular mechanism of IVIg and Tregitopes on Tregs and the secretion of IL-10 and TGF-ß1 in GBS.

PPAR Gamma-Regulated MicroRNA 199a-5p Underlies Bone Marrow Adiposity in Aplastic Anemia.

Increased propensity of bone marrow-derived mesenchymal stem cells (BM-MSCs) toward adipogenic differentiation has been implicated in the fatty bone marrow and defective hematopoiesis of aplastic anemia (AA). However, the underlying molecular mechanism remains to be investigated. In this study, we found that microRNA 199a-5p (miR-199a-5p) exhibits significantly higher expression in AA BM-MSCs compared with the normal control and is demonstrated to facilitate adipogenic differentiation of BM-MSCs through lentivirus-mediated miR-199a overexpression. Mechanistic investigation reveals that miR-199a-5p could be regulated by PPAR gamma (PPARγ) in a transcription-independent manner and regulates adipogenic differentiation by targeting the expression of transforming growth factor beta induced (TGFBI), which is subsequently validated as a negative regulator of adipogenesis. Besides, the positive correlation between PPARγ and miR-199a-5p expression as well as the inverse relationship between miR-199a-5p and TGFBI expression in normal and AA BM-MSCs was observed. Altogether, our work demonstrates that PPARγ-regulated miR-199a-5p promotes adipogenesis of BM-MSCs by inhibiting TGFBI expression, which might be a novel mechanism underlying the bone marrow adiposity in AA, and provides promising therapeutic targets for AA treatment.

Viral capsid-like titania for selective enrichment of phosphorylated peptides.

Viral capsid-like materials have been recognized as bionanotechnology platforms with great potential in controlled drug release, gene transfer and bioimaging. However, their functions still need to be optimized in aspects such as efficient drug transfer and selective targeting. Herein, we report a simple alternative strategy to fabricate viral capsid-like titania (VCL-TiO2) bearing ordered mesoporous channels and protrusions on its surface. The morphology of the synthesized titania materials matches nearly perfectly the outer surface of a real viral capsid. In particular, the robust VCL-TiO2 exhibits high porosity and a high degree of monodispersity in its particle size which makes it ideal for selectively and efficiently enriching phosphorylated peptides (PPs). Moreover, the microsized VCL-TiO2 could be easily collected and recycled through centrifugation.