Targeting hypoxia and thrombospondin-2 in diabetic wound healing.

Impaired wound healing in diabetic patients is the leading cause of diabetes-associated hospitalizations and approximately 50% of lower limb amputations. This is due to multiple factors, including elevated glucose, sustained hypoxia, and cell dysfunction. Previously, diabetic wounds were found to contain excessive levels of the matricellular protein thrombospondin-2 (TSP2) and genetic ablation of TSP2 in diabetic mice or treatment of wounds with a hydrogel derived from TSP2-null mouse skin improved healing. Previously, TSP2 has been shown to be repressed by hypoxia, but in the present study we observed sustained hypoxia and overlapping TSP2 deposition in diabetic wounds. We determined this observation was due to the insufficient HIF-1α activation verified by western blot and immunofluorescent analysis of wound tissues and in vitro hypoxia experiments. Application of Dimethyloxalylglycine (DMOG), which can stabilize HIF-1α, inhibited TSP2 expression in diabetic fibroblasts in hypoxic conditions. Therefore, we prepared DMOG-containing TSP2KO hydrogel and applied it to the wounds of diabetic mice. In comparison to empty TSP2KO hydrogel or DMOG treatment, we observed improved wound healing associated with a reduction of TSP2, reduced hypoxia, and increased neovascularization. Overall, our findings shed light on the intricate interplay between hyperglycemia, hypoxia, and TSP2 in the complex environment of diabetic wounds.

Diagnostic value of high-resolution ultrasound combined with multi-slice computer tomography (MSCT) for pediatric intra-abdominal hernias: a retrospective study.

INTRODUCTION: To explore the diagnostic value of high-resolution ultrasound combined with multi-slice computer tomography (MSCT) for pediatric intra-abdominal hernias (IAHs), and to analyze the potential causes for missed diagnosis and misdiagnosis of IAHs in children. METHODS: A retrospective analysis was conducted on 45 children with surgically confirmed IAHs. The diagnostic rate of IAHs by preoperative high-resolution ultrasound combined with MSCT was compared with that of intraoperative examination, and the potential causes for missed diagnosis and misdiagnosis by the combination method were analyzed. RESULTS: Forty-five cases of pediatric IAHs were categorized into primary (25/45, 55.5%) and acquired secondary hernias (20/45, 44.5%). Among children with primary hernias, mesenteric defects were identified as the predominant subtype (40%). Acquired secondary hernias typically resulted from abnormal openings in the abdominal wall or band adhesions due to trauma, surgery, or inflammation. In particular, adhesive band hernias were the major type in children with acquired secondary hernias (40%). The diagnostic rate of high-resolution ultrasound was 77.8%, with "cross sign" as a characteristic ultrasonic feature. Among 10 cases of missed diagnosis or misdiagnosis, 5 were finally diagnosed as IAHs by multi-slice computer tomography (MSCT). Overall, the diagnostic rate of pediatric IAHs by preoperative ultrasound combined with radiological imaging reached 88.9%. DISCUSSION: IAHs in children, particularly mesenteric defects, are prone to strangulated intestinal obstruction and necrosis. High-resolution ultrasound combined with MSCT greatly enhances the diagnostic accuracy of pediatric IAHs.

Global, regional, and national incidence and prevalence of systemic sclerosis.

OBJECTIVES: To estimate the global and country-specific unbiased epidemiological data of SSc. METHODS: Epidemiological studies were systematically searched in four databases. A Bayesian hierarchical linear mixed model was constructed to estimate epidemiological data. RESULTS: 82 studies were included and epidemiological data on SSc were missing for 83.9% of countries worldwide. The global SSc incidence and newly diagnosed population were estimated to be 8.64 per 100,000 person-years (1.78-23.57) and 0.67 million (0.14-1.84) people annually, respectively. Regarding prevalence, the global SSc prevalence and affected population were 18.87 per 100,000 persons (1.55-25.28) and 1.47 million (0.12-1.97) people, respectively. Relatively higher incidence and prevalence were observed in females, adults, and high-income level countries. CONCLUSIONS: We provide a comprehensive synthesis of SSc epidemiology and fill data gaps in most countries. Especially in low- and middle-income countries, epidemiological studies of SSc are insufficient. Further large-scale and standardized reported epidemiological investigations of SSc are imperative.

Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study.

OBJECTIVES: To quantify global, regional and country-specific estimates of epidemiology of systemic lupus erythematosus (SLE). METHODS: Four databases were systematically searched, and a Bayesian hierarchical linear mixed model was constructed to estimate the global, regional, and country-specific incidence and prevalence of SLE. RESULTS: 112 studies met the inclusion criteria. The global SLE incidence and newly diagnosed population were estimated to be 5.14 (1.4 to 15.13) per 100 000 person-years and 0.40 million people annually, respectively. In women, the values were 8.82 (2.4 to 25.99) per 100 000 person-years and 0.34 million people annually, while in men, the estimates were 1.53 (0.41 to 4.46) per 100 000 person-years and 0.06 million people annually, respectively. Poland, the USA and Barbados had the highest estimates of SLE incidence. Regarding prevalence, the global SLE prevalence and affected population were estimated to be 43.7 (15.87 to 108.92) per 100 000 persons and 3.41 million people, respectively. In women, the values were 78.73 (28.61 to 196.33) per 100 000 persons and 3.04 million people, while in men the estimates were 9.26 (3.36 to 22.97) per 100 000 persons and 0.36 million people, respectively. The United Arab Emirates, Barbados and Brazil had the highest SLE prevalence. In addition to regional and sex differences, age and prevalence estimation method (period or point prevalence) differences could also lead to variations in epidemiological SLE findings. CONCLUSIONS: Epidemiological data on SLE are lacking for 79.8% of countries worldwide. The epidemiology of SLE varies substantially between different sex and age groups and is distributed unequally among geographical regions; specifically, SLE occurs more frequently in high-income countries.

ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms.

The balance between excitatory and inhibitory (E/I) signaling is important for maintaining homeostatic function in the brain. Indeed, dysregulation of inhibitory GABA interneurons in the amygdala has been implicated in human mood disorders. We hypothesized that acetylcholine (ACh) signaling in the basolateral amygdala (BLA) might alter E/I balance resulting in changes in stress-sensitive behaviors. We therefore measured ACh release as well as activity of calmodulin-dependent protein kinase II (CAMKII)-, parvalbumin (PV)-, somatostatin (SOM)- and vasoactive intestinal protein (VIP)-expressing neurons in the BLA of awake, behaving male mice. ACh levels and activity of both excitatory and inhibitory BLA neurons increased when animals were actively coping, and decreased during passive coping, in the light-dark box, tail suspension and social defeat. Changes in neuronal activity preceded behavioral state transitions, suggesting that BLA activity may drive the shift in coping strategy. In contrast to exposure to escapable stressors, prolonging ACh signaling with a cholinesterase antagonist changed the balance of activity among BLA cell types, significantly increasing activity of VIP neurons and decreasing activity of SOM cells, with little effect on CaMKII or PV neurons. Knockdown of α7 or ß2-containing nAChR subtypes in PV and SOM, but not CaMKII or VIP, BLA neurons altered behavioral responses to stressors, suggesting that ACh signaling through nAChRs on GABA neuron subtypes contributes to stress-induced changes in behavior. These studies show that ACh modulates the GABAergic signaling network in the BLA, shifting the balance between SOM, PV, VIP and CaMKII neurons, which are normally activated coordinately during active coping in response to stress. Thus, prolonging ACh signaling, as occurs in response to chronic stress, may contribute to maladaptive behaviors by shifting the balance of inhibitory signaling in the BLA.

Global epidemiology of atopic dermatitis: a comprehensive systematic analysis and modelling study.

BACKGROUND: Atopic dermatitis (AD) is the leading cause of the global burden from skin disease; no study has provided global and country-specific epidemiological estimates of AD. OBJECTIVES: To quantify global, regional and country-specific estimates of the epidemiology of AD. METHODS: A comprehensive search for epidemiological studies in AD was conducted in four electronic databases (PubMed, Embase, Web of Science and China National Knowledge Infrastructure). A Bayesian hierarchical linear mixed model was constructed to calculate epidemiological estimates of AD considering the heterogeneity of regions, countries, type of diagnoses and age strata. RESULTS: In total, 344 studies met the inclusion criteria. Incidence varied substantially with the location and age of the surveyed participants. The global prevalence of AD and the population affected by AD were estimated to be 2.6% [95% uncertainty interval (UI) 1.9-3.5] and 204.05 million people, respectively. Around 101.27 million adults and 102.78 million children worldwide have AD, corresponding to prevalence rates of 2.0% (95% UI 1.4-2.6) and 4.0% (95% UI 2.8-5.3), respectively. Females were more likely to suffer from AD than males: the global prevalence of AD in females was 2.8% (95% UI 2.0-3.7%) and affected 108.29 million people, while in males the corresponding estimates were 2.4% (95% UI 1.7-3.3%) and 95.76 million people. CONCLUSIONS: Epidemiological AD data are lacking in 41.5% of countries worldwide. The epidemiology of AD varies substantially with age and sex and is distributed unequally across geographical regions.

Rolipram suppresses migration and invasion of human choriocarcinoma cells by inhibiting phosphodiesterase 4-mediated epithelial-mesenchymal transition.

Rolipram is a selective phosphodiesterase-4 (PDE4) inhibitor. The effect of rolipram on the metastasis of choriocarcinoma is barely known. Here, we evaluated the role of rolipram in the migration and invasion of human choriocarcinoma cells in vitro. Human choriocarcinoma cells lines JEG3 and JAR were used in this study. The expression profile of PDE4 subfamily members in choriocarcinoma cells was evaluated using real-time PCR. The migration and invasion properties of choriocarcinoma cells before and after inhibition of PDE4 by rolipram or RNAi-directed knockdown were evaluated in vitro. Expression levels of MMP9, TIMP1, E-cadherin, vimentin, TGFß1, SMAD1, and SMAD4 of choriocarcinoma cells were compared before and after rolipram treatment, RNAi-directed knockdown of PDE4D, and overexpression of PDE4D. We found PDE4D was the most commonly expressed isoform of PDE4 both in JEG3 and JAR cells. Rolipram and knockdown of PDE4D were efficient to inhibit the migration and invasion of choriocarcinoma cells in vitro, accompanied by decreased expression of MMP9 and TIMP1. Furthermore, rolipram and knockdown of PDE4D promoted the expression of E-cadherin but reduced the expression of vimentin in choriocarcinoma cells, and overexpression of PDE4D decreased the expression of E-cadherin but promoted the expression of vimentin. Rolipram suppressed migration and invasion of human choriocarcinoma cells in vitro, possibly by inhibiting epithelial-mesenchymal transition through PDE4 inhibition.

Synthesis of 5-(1-Alkoxyalkylidene)tetronates by Direct Condensation Reactions of Tetronates with Thionolactones and Thionoesters.

We report a two-step approach to bicyclic and monocyclic 5-(1-alkoxyalkylidene)tetronates starting from lactones/esters. The method features the use of thionolactones and thionoesters as activated forms of lactones/esters that allows the direct condensation with tetronates via one-pot enolate formation, nucleophilic addition, S-methylation, and DBU-promoted elimination. The value of the method was demonstrated by the stereoselective syntheses of two natural products: 5,6-Z-fadyenolide (Z/E ratio = 6:1) and 9,10-methylenedioxy-5,6-Z-fadyenolide (Z/E ratio = 9:1).

lncRNA DLG1-AS1 Promotes Cell Proliferation by Competitively Binding with miR-107 and Up-Regulating ZHX1 Expression in Cervical Cancer.

BACKGROUND/AIMS: Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in the occurrence and development of various tumors, thereby attracting increasing attention from researchers. The important biological functions of lncRNAs have been recognized gradually, but their mechanism in cervical cancer remains unclear. METHODS: Differentially expressed lncRNAs in cervical cancer and para-carcinoma tissues were identified by screening using an lncRNA array, and candidate lncRNAs were verified by quantitative real-time PCR. A series of bioinformatics and molecular biological methods were adopted to investigate the interactions among lncRNAs, microRNAs (miRNAs), and miRNA target genes in cervical cancer. Cell viability was measured using a Cell Counting Kit-8 assay. RESULTS: DLG1-AS1 was the most significantly up-regulated lncRNA in cervical cancer tissues, and it was confirmed that cervical cancer patients with high DLG1-AS1 expression had a poor prognosis. Down-regulation of DLG1-AS1 expression suppressed the proliferation of cervical cancer cells. Further investigation revealed that DLG1-AS1 eliminated the inhibition of miR-107 on the expression of its target gene ZHX1 by competitively binding to miR-107. Moreover, rescue assays proved that the effect of DLG1-AS1 on the proliferation of cervical cancer cells was dependent on miR-107. CONCLUSION: DLG1-AS1/miR-107/ZHX1 can form a competitive endogenous RNA network that regulates the proliferation of cervical cancer cells, resulting in tumor progression.

Magnesium sulphate can alleviate oxidative stress and reduce inflammatory cytokines in rat placenta of intrahepatic cholestasis of pregnancy model.

PURPOSE: In our study, we try to investigate whether magnesium sulphate (MgSO4) could provide protection against oxidative damage and inflammatory response in rat placenta of intrahepatic cholestasis of pregnancy (ICP) model. METHODS: The rat model of ICP was established by injecting s.c. 17α-ethinyl estradiol (EE) daily for 5 days. MgSO4, as an therapeutic drug for ICP, was injected i.p. daily for 3 days. Age-matched pregnant rats served as controls. The level of serum total bile acid (TBA) was measured. The data including the number and weight of offsprings on day 20 of pregnancy were collected. We observed ultrastructural changes of mitochondria and endoplasmic reticulum (ER) in placenta by transmission electron microscope. The antioxidant proteins peroxiredoxin-6 (Prdx6) and nuclear factor erythroid 2-related factor-2 (Nrf2) were analyzed by Western Blot. The inflammatory cytokines including IL-1ß, TNF-α and IFN-γ were investigated by real-time PCR (RT-PCR) and enzyme-linked immune-sorbent assay (ELISA). RESULTS: The weight of offsprings on day 20 of pregnancy increased in ICP rats treated with MgSO4 (ICP + MG group) compared with that in ICP rats (ICP group). However, the level of TBA was not reduced. The damage of mitochondria and ER was observed in placenta, which was much more slighter in ICP + MgSO4 group as compared with that in ICP group. Prdx6 and Nrf2 were increased, while the inflammatory cytokines including IL-1ß, TNF-α and IFN-γ were decreased in ICP + MgSO4 group compared with that in ICP group. CONCLUSIONS: MgSO4 had beneficial effect on improving growth of offsprings in rat model of ICP. The protective effect of MgSO4 on alleviating oxidative damage and inflammatory response in placenta may play an important role in the process. MgSO4 may improve the function of placenta.

Proteomic analysis of sputum reveals novel biomarkers for various presentations of asthma.

BACKGROUND: It is now recognized that asthma can present in different forms. Typically, asthma present with symptoms of wheeze, breathlessness and cough. Atypical forms of asthma such as cough variant asthma (CVA) or chest tightness variant asthma (CTVA) do not wheeze. We hypothesize that these different forms of asthma may have distinctive cellular and molecular features. METHODS: 30 patients with typical or classical asthma (CA), 27 patients with CVA, 30 patients with CTVA, and 30 healthy control adults were enrolled in this prospective study. We measured serum IgE, lung function, sputum eosinophils, nitric oxide in exhaled breath (FeNO). We performed proteomic analysis of induced-sputum supernatants by mass spectrometry. RESULTS: There were no significant differences in atopy and FEV1 among patients with CA, CVA, and CTVA. Serum IgE, sputum eosinophil percentages, FeNO, anxiety and depression scores were significantly increased in the three presentations of asthmatic patients as compared with healthy controls but there was no difference between the asthmatic groups. Comprehensive mass spectrometric analysis revealed more than a thousand proteins in the sputum from patients with CA, CVA, and CTVA, among which 23 secreted proteins were higher in patients than that in controls. CONCLUSIONS: Patients with CA, CVA, or CTVA share common clinical characteristics of eosinophilic airway inflammation. And more importantly, their sputum samples were composed with common factors with minor distinctions. These findings support the concept that these three different presentations of asthma have similar pathogenetic mechanism in terms of an enhanced Th2 associated with eosinophilia. In addition, this study identified a pool of novel biomarkers for diagnosis of asthma and to label its subtypes. Trial registration http://www.chictr.org.cn (ChiCTR-OOC-15006221).

[Small-world properties of the brain functional networks in patients with chronic ischemic stroke].

OBJECTIVE: To explore the characteristics of small-world properties of the brain functional networks in patients with chronic ischemic stroke. METHODS: A total of 42 stroke patients and 25 matched healthy volunteers were scanned with BOLD-fMRI and the whole-brain functional networks were constructed.Two sample t-tests were used to evaluate the changes.The properties including Eglobal, Elocal, Lp, Cp, γ, λ, σ. RESULTS: Within 0.1≤sparsity≤0.2, both groups satisfied the small-world properties(σ>1). However, the Cp and Elocal of stroke group was significantly lower (P<0.05). CONCLUSIONS: The networks in both groups still satisfied the small-world but parts of the properties in patients have changed. The reduced properties including Cp and Elocal.These changes will provide a new perspective for pathophysiological mechanism and also be helpful for understanding this disease.

[Aberrant topological properties of whole-brain functional network in chronic right-sided sensorineural hearing loss: a resting-state functional MRI study].

OBJECTIVE: To investigate the topological properties of the functional brain network in unilateral sensorineural hearing loss patients. METHODS: In this study, we acquired resting-state BOLD- fMRI data from 19 right-sided SNHL patients and 31 healthy controls with normal hearing and constructed their whole brain functional networks. Two-sample two-tailed t-tests were performed to investigate group differences in topological parameters between the USNHL patients and the controls. Partial correlation analysis was conducted to determine the relationships between the network metrics and USNHL-related variables. RESULTS: Both USNHL patients and controls exhibited small-word architecture in their brain functional networks within the range 0. 1 - 0. 2 of sparsity. Compared to the controls, USNHL patients showed significant increase in characteristic path length and normalized characteristic path length, but significant decrease in global efficiency. Clustering coefficient, local efficiency and normalized clustering coefficient demonstrated no significant difference. Furthermore, USNHL patients exhibited no significant association between the altered network metrics and the duration of USNHL or the severity of hearing loss. CONCLUSION: Our results indicated the altered topological properties of whole brain functional networks in USNHL patients, which may help us to understand pathophysiologic mechanism of USNHL patients.

Brønsted Acid Catalyzed Asymmetric Synthesis of Cyclopentenones with C4-Quaternary Centers Starting from Vinyl Sulfoxides and Allenyl Ketones or Allenoates.

Starting with chiral vinyl sulfoxides and allenyl ketones or allenoates, a triflic acid-catalyzed asymmetric [3,3]-sigmatropic rearrangement of sulfoniums is reported to have a direct access to highly functionalized C4-chiral cyclopentenones (19 examples, up to 85% yield and >95% enantiomeric excesses). In addition to the use of these chiral compounds as key building blocks in organic synthesis, the antiproliferative activities of sulfoxide substrates and the corresponding cyclopentenones were evaluated, and promising cytotoxicity against the HL-60 human tumor cell line was found.

Effects of perceived stress on college students' sleep quality: a moderated chain mediation model.

BACKGROUND: Perceived Stress has been shown as a key contributor to sleep quality, but the underlying mechanism between perceived stress and sleep quality remains unknown. This study aimed to investigate the impact of perceived stress on sleep quality of college students and the chain mediating roles of presence of meaning in life (PML) and depression, as well as the moderating role of search for meaning in life (SML). METHODS: Participants were 8178 college students (4599 boys and 3579 girls; Mage = 19.10 years, SD = 1.08) who completed self-report questionnaire, including the Perceived Stress Scale (PSS), the Pittsburgh Sleep Quality Index (PSQI), the Meaning in Life Questionnaire (MLQ), and the Patient Health Questionnaire-9 (PHQ-9). RESULTS: The results showed that higher perceived stress was directly related to poorer sleep quality. This negative impact on sleep quality was mediated through the chained roles of PML and depression. Additionally, the study found that SML moderates the influence of perceived stress, PML and depression on sleep quality. Specifically, for individuals actively search for meaning, the adverse effects of perceived stress and depression on sleep quality are diminished. Concurrently, the positive influence of PML on sleep quality is enhanced. CONCLUSION: This study revealed that the PML and depression mediate the effect of perceived stress on sleep quality, with SML playing a significant protective role. These results emphasize the necessity of integrating strategies to enhance PML and SML into interventions designed to improve emotion management and sleep quality among college students.

Mitochondrial transfer in the progression and treatment of cardiac disease.

Mitochondria are the primary site for energy production and play a crucial role in supporting normal physiological functions of the human body. In cardiomyocytes (CMs), mitochondria can occupy up to 30 % of the cell volume, providing sufficient energy for CMs contraction and relaxation. However, some pathological conditions such as ischemia, hypoxia, infection, and the side effect of drugs, can cause mitochondrial dysfunction in CMs, leading to various myocardial injury-related diseases including myocardial infarction (MI), myocardial hypertrophy, and heart failure. Self-control of mitochondria quality and conversion of metabolism pathway in energy production can serve as the self-rescue measure to avoid autologous mitochondrial damage. Particularly, mitochondrial transfer from the neighboring or extraneous cells enables to mitigate mitochondrial dysfunction and restore their biological functions in CMs. Here, we described the homeostatic control strategies and related mechanisms of mitochondria in injured CMs, including autologous mitochondrial quality control, mitochondrial energy conversion, and especially the exogenetic mitochondrial donation. Additionally, this review emphasizes on the therapeutic effects and potential application of utilizing mitochondrial transfer in reducing myocardial injury. We hope that this review can provide theoretical clues for the developing of advanced therapeutics to treat cardiac diseases.

Rapid UV Photo-Cross-Linking of α-Lactalbumin Hydrogel Biomaterial To Enable Wound Healing.

Although both the function and biocompatibility of protein-based biomaterials are better than those of synthetic materials, their usage as medical material is currently limited by their high costs, low yield, and low batch-to-batch reproducibility. In this article, we show how α-lactalbumin (α-LA), rich in tryptophan, was used to produce a novel type of naturally occurring, protein-based biomaterial suitable for wound dressing. To create a photo-cross-linkable polymer, α-LA was methacrylated at a 100-g batch scale with >95% conversion and 90% yield. α-LAMA was further processed using photo-cross-linking-based advanced processing techniques such as microfluidics and 3D printing to create injectable hydrogels, monodispersed microspheres, and patterned scaffolds. The obtained α-LAMA hydrogels show promising biocompatibility and degradability during in vivo testing. Additionally, the α-LAMA hydrogel can accelerate post-traumatic wound healing and promote new tissue regeneration. In conclusion, cheap and safe α-LAMA-based biomaterials could be produced, and they have a beneficial effect on wound healing. As a result, there may arise a potential partnership between the dairy industry and the development of pharmaceuticals.

Novel muscle-derived extracellular matrix hydrogel promotes angiogenesis and neurogenesis in volumetric muscle loss.

Volumetric muscle loss (VML) represents a clinical challenge due to the limited regenerative capacity of skeletal muscle. Most often, it results in scar tissue formation and loss of function, which cannot be prevented by current therapies. Decellularized extracellular matrix (DEM) has emerged as a native biomaterial for the enhancement of tissue repair. Here, we report the generation and characterization of hydrogels derived from DEM prepared from WT or thrombospondin (TSP)-2 null muscle tissue. TSP2-null hydrogels, when compared to WT, displayed altered architecture, protein composition, and biomechanical properties and allowed enhanced invasion of C2C12 myocytes and chord formation by endothelial cells. They also displayed enhanced cell invasion, innervation, and angiogenesis following subcutaneous implantation. To evaluate their regenerative capacity, WT or TSP2 null hydrogels were used to treat VML injury to tibialis anterior muscles and the latter induced greater recruitment of repair cells, innervation, and blood vessel formation and reduced inflammation. Taken together, these observations indicate that TSP2-null hydrogels enhance angiogenesis and promote muscle repair in a VML model.

CD47-SIRPα signaling-inspired engineered monocytes for preventing the progression of atherosclerotic plaques.

The accumulation of foam cells in the subendothelial space of the vascular wall to form plaques is the real cause of atherosclerotic lesions. Conventional interventions, such as statins and anti-cytokine or anti-inflammatory therapies, suffer problems in terms of their short therapeutic outcomes and potential disruption of the immune system. The development of more efficient therapeutics to restrict the initial progression of plaques appears to be crucial for treating and preventing atherosclerosis. Decreasing foam cell formation by reversing the excessive phagocytosis of modified low-density lipoprotein (LDL) in macrophages is highly desirable. Here, we developed a strategy based on engineered monocytes to dynamically regulate lipid uptake by macrophages inspired by a CD47-SIRPα signaling-induced defect in the phagocytosis of lesional macrophages at the advanced stage of AS. Briefly, a complex called CD47p-GQDs-miR223, which is designed to interact with SIRPα, was synthesized to remodel monocytes by decreasing the uptake of oxidized LDL through the activation of CD47-SIRPα signaling. After injection, these monocytes compete for recruitment to atherosclerotic plaques, release gene drugs and mediate anti-inflammatory phenotypic remodeling of the aboriginal macrophages, effectively inhibiting the development of foam cells. Our strategy provides a new therapeutic for preventing the progression of atherosclerosis.

A Flow-based Truncated Denoising Diffusion Model for super-resolution Magnetic Resonance Spectroscopic Imaging.

Magnetic Resonance Spectroscopic Imaging (MRSI) is a non-invasive imaging technique for studying metabolism and has become a crucial tool for understanding neurological diseases, cancers and diabetes. High spatial resolution MRSI is needed to characterize lesions, but in practice MRSI is acquired at low resolution due to time and sensitivity restrictions caused by the low metabolite concentrations. Therefore, there is an imperative need for a post-processing approach to generate high-resolution MRSI from low-resolution data that can be acquired fast and with high sensitivity. Deep learning-based super-resolution methods provided promising results for improving the spatial resolution of MRSI, but they still have limited capability to generate accurate and high-quality images. Recently, diffusion models have demonstrated superior learning capability than other generative models in various tasks, but sampling from diffusion models requires iterating through a large number of diffusion steps, which is time-consuming. This work introduces a Flow-based Truncated Denoising Diffusion Model (FTDDM) for super-resolution MRSI, which shortens the diffusion process by truncating the diffusion chain, and the truncated steps are estimated using a normalizing flow-based network. The network is conditioned on upscaling factors to enable multi-scale super-resolution. To train and evaluate the deep learning models, we developed a 1H-MRSI dataset acquired from 25 high-grade glioma patients. We demonstrate that FTDDM outperforms existing generative models while speeding up the sampling process by over 9-fold compared to the baseline diffusion model. Neuroradiologists' evaluations confirmed the clinical advantages of our method, which also supports uncertainty estimation and sharpness adjustment, extending its potential clinical applications.