Diagnostic and prognostic significance of serum lncRNA MBNL1-AS1 expression in patients with atherosclerosis.

BACKGROUND: Atherosclerosis (AS) is the pathological basis of many cardiovascular and cerebrovascular diseases. To further the investigation of treatments for AS, this research analyzed the role of lncRNA MBNL1-AS1. METHODS: MBNL1-AS1 expression in the serum of AS patients and healthy controls were detected by qPCR. Its diagnostic value in AS was assessed by receiver operating characteristic curve (ROC). Additionally, the link between MBNL1-AS1, carotid intima-media thickness (CIMT) and C-reactive protein (CRP) was examined using the Spearman correlation coefficient. The prognostic value of MBNL1-AS1 in AS was assessed using the Kaplan-Meier survival curve and univariate and multivariate Cox regression analysis. RESULTS: The present study consisted of 103 patients with AS and 92 healthy patients (HC) and comparison of baseline data between the two groups revealed no remarkable difference (P>0.05) except for CRP (P<0.0001). The serum of AS patients exhibited a considerably higher expression of MBNL1-AS1 in comparison to the HC group. Furthermore, MBNL1-AS1 was highly expressed in patients following higher CIMT and CRP values, which was positively linked with both, respectively (r>0.5, P<0.001). Meanwhile. MBNL1-AS1 has enhanced diagnostic accuracy in AS patients (AUC=0.893) and can be utilized as an independent prognostic factor for AS. Patients with high MBNL1-AS1 expression have a higher likelihood of cardiovascular events. (log rang P=0.0025). CONCLUSIONS: Elevated MBNL1-AS1p can be used as a potential marker for the clinical diagnosis of AS and is linked to a poor prognosis of AS.

An orally administered glucose-responsive polymeric complex for high-efficiency and safe delivery of insulin in mice and pigs.

Contrary to current insulin formulations, endogenous insulin has direct access to the portal vein, regulating glucose metabolism in the liver with minimal hypoglycaemia. Here we report the synthesis of an amphiphilic diblock copolymer comprising a glucose-responsive positively charged segment and polycarboxybetaine. The mixing of this polymer with insulin facilitates the formation of worm-like micelles, achieving highly efficient absorption by the gastrointestinal tract and the creation of a glucose-responsive reservoir in the liver. Under hyperglycaemic conditions, the polymer triggers a rapid release of insulin, establishing a portal-to-peripheral insulin gradient-similarly to endogenous insulin-for the safe regulation of blood glucose. This insulin formulation exhibits a dose-dependent blood-glucose-regulating effect in a streptozotocin-induced mouse model of type 1 diabetes and controls the blood glucose at normoglycaemia for one day in non-obese diabetic mice. In addition, the formulation demonstrates a blood-glucose-lowering effect for one day in a pig model of type 1 diabetes without observable hypoglycaemia, showing promise for the safe and effective management of type 1 diabetes.

Platelet-Drug Conjugates Engineered via One-step Fusion Approach for Metastatic and Postoperative Cancer Treatment.

The exploration of cell-based drug delivery systems for cancer therapy has gained growing attention. Approaches to engineering therapeutic cells with multidrug loading in an effective, safe, and precise manner while preserving their inherent biological properties remain of great interest. Here, we report a strategy to simultaneously load multiple drugs in platelets in a one-step fusion process. We demonstrate doxorubicin (DOX)-encapsulated liposomes conjugated with interleukin-15 (IL-15) could fuse with platelets to achieve both cytoplasmic drug loading and surface cytokine modification with a loading efficiency of over 70 % within minutes. Due to their inherent targeting ability to metastatic cancers and postoperative bleeding sites, the engineered platelets demonstrated a synergistic therapeutic effect to suppress lung metastasis and postoperative recurrence in mouse B16F10 melanoma tumor models.

The IAA17.1/HSFA5a module enhances salt tolerance in Populus tomentosa by regulating flavonol biosynthesis and ROS levels in lateral roots.

Auxin signaling provides a promising approach to controlling root system architecture and improving stress tolerance in plants. However, how the auxin signaling is transducted in this process remains unclear. The Aux indole-3-acetic acid (IAA) repressor IAA17.1 is stabilized by salinity, and primarily expressed in the lateral root (LR) primordia and tips in poplar. Overexpression of the auxin-resistant form of IAA17.1 (IAA17.1m) led to growth inhibition of LRs, markedly reduced salt tolerance, increased reactive oxygen species (ROS) levels, and decreased flavonol content. We further identified that IAA17.1 can interact with the heat shock protein HSFA5a, which was highly expressed in roots and induced by salt stress. Overexpression of HSFA5a significantly increased flavonol content, reduced ROS accumulation, enhanced LR growth and salt tolerance in transgenic poplar. Moreover, HSFA5a could rescue the defective phenotypes caused by IAA17.1m. Expression analysis showed that genes associated with flavonol biosynthesis were altered in IAA17.1m- and HAFA5a-overexpressing plants. Furthermore, we identified that HSFA5a directly activated the expression of key enzyme genes in the flavonol biosynthesis pathway, while IAA17.1 suppressed HSFA5a-mediated activation of these genes. Collectively, the IAA17.1/HSFA5a module regulates flavonol biosynthesis, controls ROS accumulation, thereby modulating the root system of poplar to adapt to salt stress.

The transcription factor PtoMYB142 enhances drought tolerance in Populus tomentosa by regulating gibberellin catabolism.

Drought stress caused by global warming has resulted in significant tree mortality, driving the evolution of water conservation strategies in trees. Although phytohormones have been implicated in morphological adaptations to water deficits, the molecular mechanisms underlying these processes in woody plants remain unclear. Here, we report that overexpression of PtoMYB142 in Populus tomentosa results in a dwarfism phenotype with reduced leaf cell size, vessel lumen area, and vessel density in the stem xylem, leading to significantly enhanced drought resistance. We found that PtoMYB142 modulates gibberellin catabolism in response to drought stress by binding directly to the promoter of PtoGA2ox4, a GA2-oxidase gene induced under drought stress. Conversely, knockout of PtoMYB142 by the CRISPR/Cas9 system reduced drought resistance. Our results show that the reduced leaf size and vessel area, as well as the increased vessel density, improve leaf relative water content and stem water potential under drought stress. Furthermore, exogenous GA3 application rescued GA-deficient phenotypes in PtoMYB142-overexpressing plants and reversed their drought resistance. By suppressing the expression of PtoGA2ox4, the manifestation of GA-deficient characteristics, as well as the conferred resistance to drought in PtoMYB142-overexpressing poplars, was impeded. Our study provides insights into the molecular mechanisms underlying tree drought resistance, potentially offering novel transgenic strategies to enhance tree resistance to drought.

Adoptive Treg therapy with metabolic intervention via perforated microneedles ameliorates psoriasis syndrome.

Regulatory T (Treg) cells underlie multiple autoimmune disorders and potentialize an anti-inflammation treatment with adoptive cell therapy. However, systemic delivery of cellular therapeutics often lacks tissue targeting and accumulation for localized autoimmune diseases. Besides, the instability and plasticity of Treg cells also induce phenotype transition and functional loss, impeding clinical translation. Here, we developed a perforated microneedle (PMN) with favorable mechanical performance and a spacious encapsulation cavity to support cell survival, as well as tunable channels to facilitate cell migration for local Treg therapy of psoriasis. In addition, the enzyme-degradable microneedle matrix could release fatty acid in the hyperinflammatory area of psoriasis, enhancing the Treg suppressive functions via the fatty acid oxidation (FAO)-mediated metabolic intervention. Treg cells administered through PMN substantially ameliorated psoriasis syndrome with the assistance of fatty acid-mediated metabolic intervention in a psoriasis mouse model. This tailorable PMN could offer a transformative platform for local cell therapy to treat a variety of diseases.

[Design of non-dispersed infrared (NDIR) methane gas sensor].

A non-dispersed infrared (NDIR) methane gas sensors system based on infrared absorption spectrum theory was designed according to single light beam and double wavelengths technology. In the system, an infrared LED IRL715 serving as the light power, a absorptive gas cell with the function of dust-proof and damp-proof and a pyroelectric detector LIM-262 are composed of optical probe. Signal condition uses active filter circuit and differential amplifier, and binomial expression fits the relation curve between methane concentration and voltage, which realizes accurate detection of gas concentration. Experiment approved that the sensor system with good consistency and applicability can detect the range of 5% methane reliably and have 0.5% of the sensitivity, possessing the conditions for industrial applications initially.