Screening and Identification of Target Gene of StTCP7 Transcription Factor in Potato.

TCP transcription factors are involved in the regulation of plant growth and development and response to stress. Previous studies showed that StTCP7 was involved in the abiotic stress response of potato and positively regulated plant tolerance to drought stress. On the basis of previous studies, this study verified the downstream target genes of StTCP7 transcription factor binding through yeast one hybridization, double luciferase and other technologies, and conducted a preliminary analysis of the downstream target genes. The results showed that the StTCP7 transcription factor could bind the promoter region of StDAM5 and StGOLS2 and regulate the expression of their genes. qRT-PCR analysis showed that the expression level of StDAM5 gene was the highest in flower stalk tissue and the lowest in leaf stalk. The expression of StGOLS2 gene was the highest in stem, the second in stalk, and the lower in root. Both StDAM5 and StGOLS2 genes responded to abiotic stress treated with 200 mM NaCl, 20% PEG-6000 and 100 µM ABA. The expression levels of target genes StDAM5 and StGOLS2 were up-regulated in StTCP7 interfered plants. The protein encoded by the target gene StDAM5 belongs to the Type II MADS-box protein, which contains 238 amino acids and is an acidic hydrophilic protein. The analysis of StDAM5 promoter region showed that the promoter region of StDAM5 gene contained cis-acting elements such as light response and abscisic acid. Subcellular localization showed that StDAM5 protein was expressed in both nucleus and cytoplasm.

Trace water in a BF3·OEt2 system: a facile access to sulfinyl alkenylsulfones from alkynes and sodium sulfinates.

A highly efficient and operationally simple method for the synthesis of ß-sulfinyl alkenylsulfones through a BF3·OEt2-promoted reaction of alkynes and sodium sulfinates is developed, successfully avoiding the complicated anhydrous treatment before the reaction and greatly simplifying the reaction conditions. As a facile and selective route to the targets, it features good functional group compatibility, mild conditions, easily available starting materials, and excellent yields. Notably, the trace water in solvent plays a key role in promoting the reaction, which provides a more practical pathway for the utilization of the BF3·OEt2 catalytic system.

Efficient Fine Tuning for Fashion Object Detection.

Pre-trained models have achieved success in object detection. However, challenges remain due to dataset noise and lack of domain-specific data, resulting in weaker zero-shot capabilities in specialized fields such as fashion imaging. We addressed this by constructing a novel clothing object detection benchmark, Garment40K, which includes more than 140,000 human images with bounding boxes and over 40,000 clothing images. Each clothing item within this dataset is accompanied by its corresponding category and textual description. The dataset covers 2 major categories, pants and tops, which are further divided into 15 fine-grained subclasses, providing a rich and high-quality clothing resource. Leveraging this dataset, we propose an efficient fine-tuning method based on the Grounding DINO framework to tackle the issue of missed and false detections of clothing targets. This method incorporates additional similarity loss constraints and adapter modules, leading to a significantly enhanced model named Improved Grounding DINO. By fine-tuning only a small number of additional adapter module parameters, we considerably reduced computational costs while achieving performance comparable to full parameter fine tuning. This allows our model to be conveniently deployed on a variety of low-cost visual sensors. Our Improved Grounding DINO demonstrates considerable performance improvements in computer vision applications in the clothing domain.

Response of the runoff process to meteorological drought: Baseflow index as an important indicator.

Runoff and baseflow are two hydrological elements most closely involved in water-resource management. Defining the response of runoff/baseflow to meteorological drought (MD) is helpful for designing precise drought resisting measures. Thus, Pearson correlation coefficients and mutual information scores between runoff/baseflow and MD in five sub-basins of the Weihe River Basin (WRB) were estimated on a weekly scale, and the best response times of runoff/baseflow to MD on annual and calendar months were determined according to the maximum degree of response. Furthermore, the spatial and seasonal differences in response characteristics in the WRB were discussed and the baseflow index (BFI) was introduced to further explain the propagation process of MD to runoff/baseflow. The results showed that (1) in addition to the response time, the transition sequences of MD propagating to runoff and baseflow varied across basins due to the specific basin properties; (2) Response time of runoff to MD was related to BFI value and showed significant seasonality and hydrological periodicity. In summer and autumn (wet season), the response was faster and stronger, whereas the opposite occurred in winter and spring (normal/dry season); (3) BFI values indicated the main path of drought propagation, explaining the variation in response time between basins and seasons; hence, it can be used to simply and effectively determine the propagation speed of MD to runoff. This study clarified the response characteristics of the runoff process to MD and enhanced our understanding of the drought propagation process, which is crucial for mitigating and managing drought-related hazards.

Analysis and simulation of the driving mechanism and ecological effects of land cover change in the Weihe River basin, China.

Land cover change (LCC) is both a consequence and a cause of global environmental change. This paper attempts to construct a framework to reveal the driving mechanism and ecological effects of different ecological factors under LCC and to explore the ecological characteristics of future LCC. A rule-mining framework based on a land expansion analysis strategy (LEAS) in the patch-generating land use simulation (PLUS) model was used to analyze the drivers of LCC. Neighborhood analysis and ecological effect index were used to investigate multiple ecological effects of LCC. Remote sensing-based ecological indices (RSEI) and the PLUS and stepwise regression model were introduced to explore and predict the integrated ecological effect of LCC. Focusing on the Weihe River basin, study's main drivers of LCC were precipitation, temperature, elevation, population, water table depth, proximity to governments and motorways, GDP, and topsoil organic carbon were the main drivers of LCC. Change directionality were similar for the effects of greenness and biomass formation but opposite for summertime and wintertime temperature. In addition, the conversion of land cover types to cropland had the most significant integrated ecological effect, followed by forest, grassland-shrubland, and other types. The RSEI is predicted to rise to 0.77 in 2030, and the areas where the ecological quality grade will improve and decrease are concentrated on the east and west sides of Ziwuling Mountain, respectively. The findings of this study have practical significance for land management and ecological protection.

Spatiotemporal variations of water conservation function based on EOF analysis at multi time scales under different ecosystems of Heihe River Basin.

Water conservation function is a critical terrestrial ecosystem service in providing water supply and achieving water security, which has raised concerns under the pressure of climate change. However, the knowledge of variance on multi-time scale, spatiotemporal dynamic, and ecosystem variance of water conservation is insufficient. In this paper, the annual, monthly, and daily scales of water conservation and the spatiotemporal pattern of monthly water conservation were estimated based on the SWAT model from 2010 to 2020 in the Heihe River Basin (HRB). Additionally, EOF (Empirical orthogonal function) analysis was conducted to decompose the time series of water conservation function distribution into temporal coefficients and spatial patterns. The HRB was categorized into six representative ecosystems with three slope grades to illustrate the variance of water conservation function. The annual water conservation depth (WC) slightly decreased (-10.36 mm/10a) from 2010 to 2020, the monthly WC was dominated by the effects of seasonal variation, and the daily WC was highly nonlinear. The high variability and importance region is mainly located in the upstream and the central area of midstream, which deserves more attention for ecological management and priority protection. Moreover, the forest ecosystem is of the highest resilience and great ecological significance, which increased risk of reduced water conservation under the lack of precipitation. Even in a forest-dominated basin, water conservation can be impacted by other ecosystems with the strong influence of human activities. Our results provide scientific evidence for the improvement of water conservation capacity and making the adapted land use policy in Yellow River basins.

Association between rs1799971 in the mu opioid receptor gene and methadone maintenance treatment response.

OBJECTIVE: Genetic variations can affect individual response to methadone maintenance treatment (MMT) for heroin addiction. The A118G variant (rs1799971) in the mu opioid receptor gene (OPRM1) is a potential candidate single nucleotide polymorphism (SNP) for personalized MMT. This study determined whether rs1799971 is related to MMT response or dose. METHODS: We recruited 286 MMT patients from a Han Chinese population. The rs1799971 genotype was determined via TaqMan genotyping assay. The genetic effect of this SNP on MMT response or dose was evaluated using logistic regression. A meta-analysis was performed to merge all available data to evaluate the role of rs1799971 in MMT using RevMan 5.3 software. RESULTS: No statistical significance was observed in the association between the OPRM1 rs1799971 and MMT response or dose in our Chinese cohort. Meta-analysis indicated that the OPRM1 A118G variation was not significantly associated with MMT response or dose requirement. CONCLUSION: The results suggest that rs1799971 in OPRM1 might not play a critical role alone in influencing MMT response or dose.

PEGylated Nanoscale Metal-Organic Frameworks for Targeted Cancer Imaging and Drug Delivery.

Nanoscale metal-organic frameworks (nMOFs) are a unique type of hybrid materials, which are broadly applicable as cargo delivery systems. However, the relatively low material stability and insufficient cancer cell interacting capacity have limited nMOFs' applications in cancer theranostics. Herein, a zirconium-based nMOF UiO-66-N3 was synthesized, and its surface was covalently functionalized with alkyne-containing polyethylene glycol (PEG) via the azide-alkyne click chemistry. After that, F3 peptide was attached for targeting of cancer cells (the material was denoted as UiO-66-PEG-F3). Doxorubicin (DOX) served as a therapeutic drug and a fluorescent label in this study, and it was transported into UiO-66-PEG conjugates with sufficient drug loading efficiency. pH-responsive release of DOX from UiO-66 conjugates was witnessed. The structural integrity of UiO-66-N3 was maintained post the surface modification process. Flow cytometry and confocal fluorescence microscopy revealed that DOX/UiO-66-PEG-F3 had stronger accumulation in MDA-MB-231 cells (nucleolin+) compared with DOX/UiO-66-PEG. In order to track the pharmacokinetic behavior (organ distribution profile) in vivo, the positron-emitting zirconium-89 (89Zr) was incorporated into UiO-66-N3. Similar PEGylation and F3 peptide conjugation resulted in the formation of 89Zr-UiO-66-PEG-F3. Serial positron emission tomography (PET) imaging demonstrated that the preferential accumulation of 89Zr-UiO-66-PEG-F3 in MDA-MB-231 tumors, and their liver clearance was faster than PEGylated UiO-66 using noncovalent methods. Thus, the PEGylated nMOFs using covalent strategies may find broad application in future cancer theranostics.

Increased expression of plasma hsa-miR-181a in male patients with heroin addiction use disorder.

BACKGROUND: Drug addiction is an uncontrolled, chronic, and recurrent encephalopathy that presently lacks specific and characteristic biomarkers for diagnosis and treatment. As regulators of gene expression, microRNAs (miRNAs) are increasingly used for diagnostic and prognostic purposes in various disease states. Previous studies indicated that miRNAs play important roles in the development and progression of drug addictions, including addiction to methamphetamine, cocaine, alcohol, and heroin. METHODS: We identified significant miRNAs using the microarray method and then validated the hsa-miR-181a expression levels in 53 heroin addiction patients and 49 normal controls using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the potential associations between transcriptional levels in heroin addiction patients and their clinicopathological features were analyzed. RESULTS: A total of 2006 miRNAs were differentially expressed between heroin addiction patients and normal controls. The top 10 up-regulated miRNAs in patients were hsa-miR-21a, hsa-miR-181a, hsa-miR-4459, hsa-miR-4430, hsa-miR-4306, hsa-miR-22-3P, hsa-miR-486-5P, hsa-miR-371b-5P, hsa-miR-92a-3P, and hsa-miR-5001-5P. The top 10 down-regulated miRNAs in patients were hsa-miR-3195, hsa-miR-4767, hsa-miR-3135b, hsa-miR-6087, hsa-miR-1181, hsa-miR-4785, hsa-miR-718, hsa-miR-3141, hsa-miR-652-5P, and hsa-miR-6126. The expression level of hsa-miR-181a in heroin addiction patients was significantly increased compared with that in normal controls (P < .001). The area under the receiver operating characteristic curve of hsa-miR-181a was 0.783, the sensitivity was 0.867, and the specificity was 0.551. CONCLUSIONS: The increased expression of hsa-miR-181a in the plasma of heroin patients may be a consequence of the pathological process of heroin abuse. This study highlights the potential of hsa-miR-181a as a novel biomarker for the diagnosis of heroin addiction.

General Approach to Prepare 0.33Li2MnO3 · 0.67LiNi1/3Co1/3Mn1/3O2 Hollow Microspheres for High Performance Lithium Ion Batteries.

Li-excess manganese-based oxide layered structures, have drawn increasing interests as the promising cathodes to succeed the conventional LiCoO2 in lithium ion batteries (LIBs). It could deliver a higher energy density and output potential, as well as the nature of environment benign and low cost. Pristine Li-excess manganese-based oxides however suffer from poor rate capacity and voltage fading after cycling, and their inherent capacity limits of bulk size in performance. Micro-/Nanostructured electrode materials are considered to hold the key to overcome these thresholds. This paper reports a general approach to prepare 0.33Li2MnO3 · 0.67LiNi1/3Co1/3Mn1/3O2 microspheres with pores and void space, which benefits improving both the capacity and cyclability. The electrode made of hollow 0.33Li2MnO3 · 0.67LiNi1/3Co1/3Mn1/3O2 microspheres exhibits a 224 mAh g-1 discharge capacity over 200 cycles at 0.25 C rate, and 195 mAh g-1 at 5.0 C rate. These results indicated good perspective of hollow microspheres for practical battery applications.

Inverted Micelle-in-Micelle Configuration in Cationic/Carbohydrate Surfactant Mixtures.

Nuclear magnetic resonance is applied to investigate the relative positions and interactions between cationic and non-ionic carbohydrate-based surfactants in mixed micelles with D2 O as the solvent. This is accomplished by using relaxation measurements [spin-lattice (T1 ) and spin-spin (T2 ) analysis] and nuclear Overhauser effect spectroscopy (NOESY). This study focuses on the interactions of n-octyl ß-d-glucopyranoside (C8G1) and ß-d-xylopyranoside (C8X1) with the cationic surfactant hexadecyltrimethylammonium bromide (C16 TAB). Whereas the interactions between carbohydrate and cationic surfactants are thermodynamically favorable, the NOESY results suggest that both of the sugar head groups are located preferentially at the interior core of the mixed micelles, so that they are not directly exposed to the bulk solution. The more hydrophilic sugar headgroups of C8G1 have more mobility than sugar heads of C8X1 owing to increased hydration. Herein, an inverted carbohydrate configuration in mixed micelles is proposed for the first time and supported by fluorescence spectroscopy experiments. This inverted carbohydrate headgroup configuration would limit the use of these mixed surfactants when access to the carbohydrate headgroup is important, but may present new opportunities where the carbohydrate-rich core of the micelles can be exploited.

Glutamatergic transmission aberration: a major cause of behavioral deficits in a murine model of Down's syndrome.

Trisomy 21, or Down's syndrome (DS), is the most common genetic cause of intellectual disability. Altered neurotransmission in the brains of DS patients leads to hippocampus-dependent learning and memory deficiency. Although genetic mouse models have provided important insights into the genes and mechanisms responsible for DS-specific changes, the molecular mechanisms leading to memory deficits are not clear. We investigated whether the segmental trisomy model of DS, Ts[Rb(12.1716)]2Cje (Ts2), exhibits hippocampal glutamatergic transmission abnormalities and whether these alterations cause behavioral deficits. Behavioral assays demonstrated that Ts2 mice display a deficit in nest building behavior, a measure of hippocampus-dependent nonlearned behavior, as well as dysfunctional hippocampus-dependent spatial memory tested in the object-placement and the Y-maze spontaneous alternation tasks. Magnetic resonance spectra measured in the hippocampi revealed a significantly lower glutamate concentration in Ts2 as compared with normal disomic (2N) littermates. The glutamate deficit accompanied hippocampal NMDA receptor1 (NMDA-R1) mRNA and protein expression level downregulation in Ts2 compared with 2N mice. In concert with these alterations, paired-pulse analyses suggested enhanced synaptic inhibition and/or lack of facilitation in the dentate gyrus of Ts2 compared with 2N mice. Ts2 mice also exhibited disrupted synaptic plasticity in slice recordings of the hippocampal CA1 region. Collectively, these findings imply that deficits in glutamate and NMDA-R1 may be responsible for impairments in synaptic plasticity in the hippocampus associated with behavioral dysfunctions in Ts2 mice. Thus, these findings suggest that glutamatergic deficits have a significant role in causing intellectual disabilities in DS.

Overcoming the limitations of immunotherapy in pancreatic ductal adenocarcinoma: Combining radiotherapy and metabolic targeting therapy.

As a novel anticancer therapy, immunotherapy has demonstrated robust efficacy against a few solid tumors but poor efficacy against pancreatic ductal adenocarcinoma (PDAC). This poor outcome is primarily attributable to the intrinsic cancer cell resistance and T-cell exhaustion, which is also the reason for the failure of conventional therapy. The present review summarizes the current PDAC immunotherapy avenues and the underlying resistance mechanisms. Then, the review discusses synergistic combination therapies, such as radiotherapy (RT) and metabolic targeting. Research suggests that RT boosts the antigen of PDAC, which facilitates the anti-tumor immune cell infiltration and exerts function. Metabolic reprogramming contributes to restoring the exhausted T cell function. The current review will help in tailoring combination regimens to enhance the efficacy of immunotherapy. In addition, it will help provide new approaches to address the limitations of the immunosuppressive tumor microenvironment (TME) by examining the relationship among immunotherapy, RT, and metabolism targeting therapy in PDAC.

VascuConNet: an enhanced connectivity network for vascular segmentation.

Medical image segmentation commonly involves diverse tissue types and structures, including tasks such as blood vessel segmentation and nerve fiber bundle segmentation. Enhancing the continuity of segmentation outcomes represents a pivotal challenge in medical image segmentation, driven by the demands of clinical applications, focusing on disease localization and quantification. In this study, a novel segmentation model is specifically designed for retinal vessel segmentation, leveraging vessel orientation information, boundary constraints, and continuity constraints to improve segmentation accuracy. To achieve this, we cascade U-Net with a long-short-term memory network (LSTM). U-Net is characterized by a small number of parameters and high segmentation efficiency, while LSTM offers a parameter-sharing capability. Additionally, we introduce an orientation information enhancement module inserted into the model's bottom layer to obtain feature maps containing orientation information through an orientation convolution operator. Furthermore, we design a new hybrid loss function that consists of connectivity loss, boundary loss, and cross-entropy loss. Experimental results demonstrate that the model achieves excellent segmentation outcomes across three widely recognized retinal vessel segmentation datasets, CHASE_DB1, DRIVE, and ARIA.

Alignment of Visible-Light Optical Coherence Tomography Fibergrams with Confocal Images of the Same Mouse Retina.

In recent years, in vivo retinal imaging, which provides non-invasive, real-time, and longitudinal information about biological systems and processes, has been increasingly applied to obtain an objective assessment of neural damage in eye diseases. Ex vivo confocal imaging of the same retina is often necessary to validate the in vivo findings especially in animal research. In this study, we demonstrated a method for aligning an ex vivo confocal image of the mouse retina with its in vivo images. A new clinical-ready imaging technology called visible light optical coherence tomography fibergraphy (vis-OCTF) was applied to acquire in vivo images of the mouse retina. We then performed the confocal imaging of the same retina as the "gold standard" to validate the in vivo vis-OCTF images. This study not only enables further investigation of the molecular and cellular mechanisms but also establishes a foundation for a sensitive and objective evaluation of neural damage in vivo.

Differential expression profiling of tRNA-Derived small RNAs and their potential roles in methamphetamine self-administered rats.

Transfer RNA-derived small RNAs (tsRNAs) are a novel class of short, non-coding RNAs that are closely associated with the pathogenesis of various diseases. Accumulating evidence has demonstrated their critical functional roles as regulatory factors in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress. However, the underlying mechanisms by which tRFs & tiRNAs affect methamphetamine-induced pathophysiological processes are largely unknown. In this study, we used a combination of small RNA sequencing, quantitative reverse transcription-polymerase chain reaction (qRT‒PCR), bioinformatics, and luciferase reporter assays to screen the expression profiles and identify the functional roles of tRFs and tiRNAs in the nucleus accumbens (NAc) of methamphetamine self-administration rat models. A total of 461 tRFs & tiRNAs were identified in the NAc of rats after 14 days of methamphetamine self-administration training. Of those, 132 tRFs & tiRNAs were significantly differentially expressed: 59 were significantly upregulated, whereas 73 were significantly downregulated in the rats with methamphetamine self-administration. Decreased expression levels of tiRNA-1-34-Lys-CTT-1 and tRF-1-32-Gly-GCC-2-M2, as well as increased expression levels of tRF-1-16-Ala-TGC-4 in the METH group compared with the saline control were validated by using RT‒PCR. Then, bioinformatic analysis was performed to analyse the possible biological functions of tRFs & tiRNAs in methamphetamine-induced pathogenesis. Furthermore, tRF-1-32-Gly-GCC-2-M2 was identified to target BDNF using the luciferase reporter assay. An altered tsRNA expression pattern was proven, and tRF-1-32-Gly-GCC-2-M2 was shown to be involved in methamphetamine-induced pathophysiologic processes by targeting BDNF. The current study provides new insights for future investigations to explore the mechanisms and therapeutic methods for methamphetamine addiction.

Poly(ß-amino ester) Dual-Drug-Loaded Hydrogels with Antibacterial and Osteogenic Properties for Bone Repair.

In this study, we developed a poly(ß-amino ester) (PBAE) hydrogel for the double release of vancomycin (VAN) and total flavonoids of Rhizoma Drynariae (TFRD). VAN was covalently bonded to PBAE polymer chains and was released to enhance the antimicrobial effect first. TFRD chitosan (CS) microspheres were physically dispersed in the scaffold, TFRD was released from the microspheres, and osteogenesis was induced subsequently. The scaffold had good porosity (90.12 ± 3.27%), and the cumulative release rate of the two drugs in PBS (pH 7.4) solution exceeded 80%. In vitro antimicrobial assays demonstrated the antibacterial properties of the scaffold against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Besides these, cell viability assays indicated that the scaffold had good biocompatibility. Moreover, alkaline phosphatase and matrix mineralization were expressed more than in the control group. Overall, cell experiments confirmed that the scaffolds have enhanced osteogenic differentiation capabilities. In conclusion, the dual-drug-loaded scaffold with antibacterial and bone regeneration effects is promising in the field of bone repair.

New Insight into Temperature Effects on Low-Rank Coal Flotation Using Diesel as a Collector.

Efficient flotation of low-rank coal is of great significance for the development of green and low-carbon cycles. Temperature is a crucial parameter of flotation, but the mechanism of its effect on flotation lacks understanding. In this paper, the mechanism was studied by kinetic flotation, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, low-temperature liquid-nitrogen adsorption (LP-N2A), X-ray photoelectron spectroscopy (XPS), and molecular dynamics simulation. The flotation combustible recovery gradually decreases as temperature rises. Compared with 60 °C, the combustible recovery at 5 °C increases by 18.13%. The desorption energy for oil droplets decreases as the temperature rises. As a result, the oil droplets are easier to desorb at high temperatures. The SEM and LP-N2A results demonstrate that the pores and fractures of the coal sample are well developed. Also, the oil-water interfacial tension and viscosity of oil droplets decrease as the temperature rises, while the diffusion ability increases. These increase the volume of oil droplets that penetrate into the pores, resulting in poor spreadability of oil droplets on the coal surface. The average volume of bubbles gradually increases as temperature rises, which renders the flotation foam unstable and worsens the flotation. Therefore, the flotation performance is better at low temperatures.

A pectin-based photoactivated bactericide nanosystem for achieving an improved utilization rate, photostability and targeted delivery of hematoporphyrin.

Photoactivated pesticides have many advantages, such as high activity, low toxicity, and no drug resistance. However, poor photostability and a low utilization rate limit their practical application. Herein, the photosensitizer hematoporphyrin (HP) was used as a photoactivated pesticide, covalently linked with pectin (PEC) via ester bonds, to prepare an amphiphilic polymer pro-bactericide, and subsequently self-assembled in aqueous solutions to obtain an esterase-triggered nanobactericide delivery system. The fluorescence quenching effect due to the aggregation of HP in nanoparticles (NPs) enabled the inhibition of photodegradation of HP in this system. Esterase stimulation could trigger HP release and increase its photodynamic activity. Antibacterial assays have shown that the NPs had potent antibacterial capacity, almost completely inactivating bacteria after 60 min of exposure to light. The NPs had good adherence to the leaves. Safety assessment indicated that the NPs have no obvious toxic effects on plants. Antibacterial studies on plants have shown that the NPs have excellent antibacterial effects on infected plants. These results provide a new strategy for obtaining a photoactivated bactericide nanosystem with a high utilization rate and good photostability and targeting ability.

Circulating plasma and exosome levels of the miR-320 family as a non-invasive biomarker for methamphetamine use disorder.

The neurobiological mechanism underlying methamphetamine (MA) use disorder was still unclear, and no specific biomarker exists for clinical diagnosis of this disorder. Recent studies have demonstrated that microRNAs (miRNAs) are involved in the pathological process of MA addiction. The purpose of this study was to identify novel miRNAs for the diagnosis biomarkers of MA user disorder. First, members of the miR-320 family, including miR-320a-3p, miR-320b, and miR-320c, were screened and analyzed in the circulating plasma and exosomes by microarray and sequencing. Secondly, plasma miR-320 was quantified by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) in eighty-two MA patients and fifty age-gender-matched healthy controls. Meanwhile, we also analyzed exosomal miR-320 expression in thirty-nine MA patients and twenty-one age-matched healthy controls. Furthermore, the diagnostic power was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The expression of miR-320 significantly increased in plasma and exosomes of MA patients compared with healthy controls. The AUC of the ROC curves of miR-320 in plasma and exosomes of MA patients were 0.751 and 0.962, respectively. And the sensitivities of miR-320 were 0.900 and 0.846, respectively, whereas the specificities of miR-320 were 0.537 and 0.952, respectively, in plasma and exosomes in MA patients. And the increased plasma miR-320 was positively correlated with cigarette smoking, age of onset, and daily use of MA in MA patients. Finally, cardiovascular disease, synaptic plasticity, and neuroinflammation were predicted to be the target pathways related to miR-320. Taken together, our findings indicated that plasma and exosomal miR-320 might be used as a potential blood-based biomarker for diagnosing MA use disorder.