Enhancing osteoporosis treatment using a targeted, sustained-release drug delivery system based on macrocyclic amphiphile.

Osteoporosis, a prevalent systemic bone metabolic disorder, primarily affects postmenopausal women and is characterized by increased bone fragility and a heightened risk of fractures. The efficacy of current osteoporosis treatments is often limited by non-specific drug targeting and undesirable off-target skeletal side effects. To address this challenge, we have developed a novel hydroxyapatite-responsive drug delivery system. This system utilizes a self-assembled p-phosphonatocalix[4]arene tetradodecyl ether (PC4A12C), engineered to specifically target and sustain the release of osteoporosis medication at sites of bone remodeling. Our focus centers on icariin (ICA), a drug known for its potent osteogenic properties and minimal adverse effects. In vitro, ICA-loaded PC4A12C (ICA@PC4A12C) demonstrated enhanced proliferation, differentiation, and mineralization in bone marrow mesenchymal stem cells (BMSCs). In vivo, ICA@PC4A12C exhibited superior efficacy in specifically targeting bone tissue, ensuring a controlled and slow release of icariin directly within the bone environment. In an osteoporosis mouse model, treatment with ICA@PC4A12C showed notable enhancement in osteogenic activity and a significant increase in bone density compared to ICA alone. These results demonstrate the potential of PC4A12C as an effective drug carrier in the development of advanced antiosteoporotic drug delivery systems.

A Least-Square Unified Framework for Spatial Filtering in SSVEP-Based BCIs.

The steady-state visual evoked potential (SSVEP) has become one of the most prominent BCI paradigms with high information transfer rate, and has been widely applied in rehabilitation and assistive applications. This paper proposes a least-square (LS) unified framework to summarize the correlation analysis (CA)-based SSVEP spatial filtering methods from a machine learning perspective. Within this framework, the commonalities and differences between various spatial filtering methods appear apparent, the interpretation of computational factors becomes intuitive, and spatial filters can be determined by solving a generalized optimization problem with non-linear and regularization items. Moreover, the proposed LS framework provides the foundation of utilizing the knowledge behind these spatial filtering methods in further classification/regression model designs. Through a comparative analysis of existing representative spatial filtering methods, recommendations are made for the superior and robust design strategies. These recommended strategies are further integrated to fill the research gaps and demonstrate the ability of the proposed LS framework to promote algorithmic improvements, resulting in five new spatial filtering methods. This study could offer significant insights in understanding the relationships between various design strategies in the spatial filtering methods from the machine learning perspective, and would also contribute to the development of the SSVEP recognition methods with high performance.

Pathological polarizations from microglia to astrocyte contributes to spatial memory deficit in methamphetamine abstinence mice.

Previously, we found that dCA1 A1-like polarization of astrocytes contributes a lot to the spatial memory deficit in methamphetamine abstinence mice. However, the underlying mechanism remains unclear, resulting in a lack of promising therapeutic targets. Here, we found that methamphetamine abstinence mice exhibited an increased M1-like microglia and A1-like astrocytes, together with elevated levels of interleukin 1α and tumor necrosis factor α in dCA1. In vitro, the M1-like BV2 microglia cell medium, containing high levels of Interleukin 1α and tumor necrosis factor α, elevated A1-like polarization of astrocytes, which weakened their capacity for glutamate clearance. Locally suppressing dCA1 M1-like microglia activation with minocycline administration attenuated A1-like polarization of astrocytes, ameliorated dCA1 neurotoxicity, and, most importantly, rescued spatial memory in methamphetamine abstinence mice. The effective time window of minocycline treatment on spatial memory is the methamphetamine exposure period, rather than the long-term methamphetamine abstinence.

Effects of Preoperative Oral Carbohydrates on Recovery After Laparoscopic Cholecystectomy: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: The objective of this meta-analysis was to evaluate the efficacy of administering preoperative oral carbohydrates (CHO) compared to a control treatment in improving postoperative recovery outcomes for patients undergoing laparoscopic cholecystectomy (LC). DESIGN: A meta-analysis of randomized controlled trials. METHODS: Through systematic searches in PubMed, Embase, and the Cochrane Library, randomized controlled trials focusing on preoperative oral carbohydrates for patients undergoing LC were collected. Data analysis was conducted using the Revman 5.3 software. FINDINGS: The meta-analysis incorporated 19 randomized studies, with a total of 1,568 participants. Meta-analysis results indicated that patients receiving CHO reported notably lower postoperative pain compared to those fasting (P = .006) or on placebo (P = .003). Furthermore, a significant reduction in preoperative hunger was observed in the CHO group compared to the controls (P = .002). A notable difference was also identified in the postoperative Homeostasis Model Assessment-IR changes between the CHO and control groups (P = .02). No significant variations were observed in thirst, postoperative nausea and vomiting, insulin level alterations, glucose level changes, duration of hospital stay, or recovery quality. CONCLUSIONS: Preoperative oral carbohydrates may alleviate hunger and pain, and attenuate postoperative insulin resistance more effectively than either overnight fasting or placebo in patients undergoing LC.

Molecular characterization and clinical relevance of metabolic signature subtypes in gastric cancer.

Metabolic reprogramming dictates tumor molecular attributes and therapeutic potentials. However, the comprehensive metabolic characteristics in gastric cancer (GC) remain obscure. Here, metabolic signature-based clustering analysis identifies three subtypes with distinct molecular and clinical features: MSC1 showed better prognosis and upregulation of the tricarboxylic acid (TCA) cycle and lipid metabolism, combined with frequent TP53 and RHOA mutation; MSC2 had moderate prognosis and elevated nucleotide and amino acid metabolism, enriched by intestinal histology and mismatch repair deficient (dMMR); and MSC3 exhibited poor prognosis and enhanced glycan and energy metabolism, accompanied by diffuse histology and frequent CDH1 mutation. The Shandong Provincial Hospital (SDPH) in-house dataset with matched transcriptomic, metabolomic, and spatial-metabolomic analysis also validated these findings. Further, we constructed the metabolic subtype-related prognosis gene (MSPG) scoring model to quantify the activity of individual tumors and found a positive correlation with cuproptosis signaling. In conclusion, comprehensive recognition of the metabolite signature can enhance the understanding of diversity and heterogeneity in GC.

Clinical and MRI risk factors predicting post-irradiation carotid blowout syndrome in patients with nasopharyngeal cancer.

OBJECTIVE: To explore the clinical and imaging features of nasopharyngeal cancer (NPC) complicated by acute carotid blowout syndrome (CBS), analyze the risk factors for CBS, and improve diagnostic vigilance for early intervention. METHODS: This retrospective review was conducted between January 2003 and May 2023. Altogether, 49 patients with post-irradiation NPC with CBS and 49 patients without CBS as control group were enrolled. The condition of the patients when CBS occurred was reviewed. Patient characteristics of the CBS and control groups were compared, and binary logistic regression analysis was performed to identify risk factors for CBS. RESULTS: All patients in the CBS group were conscious, and 41 patients had a Karnofsky performance assessment scale score of ≥ 70. After interventional therapy, 43 patients survived (the mean survival time of patients after CBS was 3.2 ± 2.1 years). Compared with the control group, the CBS group had a higher incidence of sphenoid sinusitis (81% vs. 52.4%), osteonecrosis (82.9% vs. 51.2%), artery exposure (29.3% vs. 4.9%), and internal carotid artery injury (61% vs. 29.3%). Osteonecrosis and artery exposure were selected as important risk factor for CBS, with p-values of 0.016 and 0.031, respectively. CONCLUSION: CBS is an important factor that affects the survival of patients with NPC. If internal carotid artery injury, artery exposure, sphenoid sinusitis, and osteonecrosis are present, especially the latter two signs, the possibility of CBS should be considered.

Analyzing noncovalent interactions between notoginseng saponins and lysozyme by deposition scanning intensity fading MALDI-TOF mass spectrometry.

Analysis of noncovalent interactions between natural products and proteins is important for rapid screening of active ingredients and understanding their pharmacological activities. In this work, the intensity fading MALDI-TOF mass spectrometry (IF-MALDI-MS) method with improved reproducibility was implemented to investigate the binding interactions between saponins from Panax notoginseng and lysozyme. The benchmark IF-MALDI-MS experiment was established using N,N',N″-triacetylchitotriose-lysozyme as a model system. The reproducibility of ion intensities in IF-MALDI-MS was improved by scanning the whole sample deposition with a focused laser beam. The relative standard deviation (RSD) of deposition scanning IF-MALDI-MS is 5.7%. Similar decay trends of the relative intensities of notoginseng saponins against increasing amounts of lysozyme were observed for all six notoginseng saponins. The half-maximal fading concentration (FC50) was calculated to quantitatively characterize the binding affinity of each ligand based on the decay curve. According to the FC50 values obtained, the binding affinities of the six notoginseng saponins were evaluated in the following order: notoginsenoside S > notoginsenoside Fc > ginsenoside Rb1 > ginsenoside Rd > notoginsenoside Ft1 > ginsenoside Rg1. The binding order was in accordance with molecular docking studies, which showed hydrogen bonding might play a key role in stabilizing the binding interaction. Our results demonstrated that deposition scanning IF-MALDI-MS can provide valuable information on the noncovalent interactions between ligands and proteins.

Calixarene-Based Supramolecular Sensor Array for Pesticide Discrimination.

The identification and detection of pesticides is crucial to protecting both the environment and human health. However, it can be challenging to conveniently and rapidly differentiate between different types of pesticides. We developed a supramolecular fluorescent sensor array, in which calixarenes with broad-spectrum encapsulation capacity served as recognition receptors. The sensor array exhibits distinct fluorescence change patterns for seven tested pesticides, encompassing herbicides, insecticides, and fungicides. With a reaction time of just three minutes, the sensor array proves to be a rapid and efficient tool for the discrimination of pesticides. Furthermore, this supramolecular sensing approach can be easily extended to enable real-time and on-site visual detection of varying concentrations of imazalil using a smartphone with a color scanning application. This work not only provides a simple and effective method for pesticide identification and quantification, but also offers a versatile and advantageous platform for the recognition of other analytes in relevant fields.

Turning foes to friends: Advanced "in situ nanovaccine" with dual immunoregulation for enhanced immunotherapy of metastatic triple-negative breast cancer.

As a "cold tumor", triple-negative breast cancer (TNBC) exhibits limited responsiveness to current immunotherapy. How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge. Herein, an "in situ nanovaccine" Au/CuNDs-R848 was designed for imaging-guided photothermal therapy (PTT)/chemodynamic therapy (CDT) synergistic therapy to trigger dual immunoregulatory effects on TNBC. On the one hand, Au/CuNDs-R848 served as a promising photothermal agent and nanozyme, achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC. Meanwhile, the released antigens and damage-associated molecular patterns (DAMPs) promoted the maturation of dendritic cells (DCs) and facilitated the infiltration of T lymphocytes. Thus, Au/CuNDs-R848 played a role as an "in situ nanovaccine" to enhance the immunogenicity of TNBC by inducing immunogenic cell death (ICD). On the other hand, the nanovaccine suppressed the myeloid-derived suppressor cells (MDSCs), thereby reversing the immunosuppressive microenvironment. Through the dual immunoregulation, "cold tumor" was transformed into a "hot tumor", not only implementing a "turning foes to friends" therapeutic strategy but also enhancing immunotherapy against metastatic TNBC. Furthermore, Au/CuNDs-R848 acted as an excellent nanoprobe, enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC. This feature offers potential applications in clinical cancer detection and surgical guidance. Collectively, this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.

Simultaneous arterial spin labeling functional MRI and fluorodeoxyglucose PET in mild chronic traumatic brain injury.

BACKGROUND AND PURPOSE: To determine the effect of mild chronic traumatic brain injury (cTBI) on cerebral blood flow and metabolism. METHODS: 62 cTBI and 40 healthy controls (HCs) with no prior history of cTBI underwent both pulsed arterial spin labeling functional magnetic resonance imaging (PASL-fMRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) scanning via a Siemens mMR (simultaneous PET/MRI) scanner. 30 participants also took part in a series of neuropsychological clinical measures (NCMs). Images were processed using statistical parametric mapping software relevant to each modality to generate relative cerebral blood flow (rCBF) and glucose metabolic standardized uptake value ratio (gSUVR) grey matter maps. A voxel-wise two-sample T-test and two-tailed gaussian random field correction for multiple comparisons was performed. RESULTS: cTBI patients showed a significant increase in rCBF and gSUVR in the right thalamus as well as a decrease in bilateral occipital lobes and calcarine sulci. An inverse relationship between rCBF and gSUVR was found in the left frontal lobe, the left precuneus and regions in the right temporal lobe. Within those regions rCBF values correlated with 9 distinct NCMs and gSUVR with 3. CONCLUSION: Simultaneous PASL-fMRI and FDG-PET can identify functional changes in a mild cTBI population. Within this population FDG-PET identified more regions of functional disturbance than ASL fMRI and NCMs are shown to correlate with rCBF and glucose metabolism (gSUVR) in various brain regions. As a result, both imaging modalities contribute to understanding the underlying pathophysiology and clinical course of mild chronic traumatic brain injury.

ASL MRI Denoising via Multi Channel Collaborative Low-Rank Regularization.

Arterial spin labeling (ASL) perfusion MRI is the only non-invasive imaging technique for quantifying regional cerebral blood flow (CBF), which is a fundamental physiological variable. ASL MRI has a relatively low signal-to-noise-ratio (SNR). In this study, we proposed a novel ASL denoising method by simultaneously exploiting the inter- and intra-receive channel data correlations. MRI including ASL MRI data have been routinely acquired with multi-channel coils but current denoising methods are designed for denoising the coil-combined data. Indeed, the concurrently acquired multi-channel images differ only by coil sensitivity weighting and random noise, resulting in a strong low-rank structure of the stacked multi-channel data matrix. In our method, this matrix was formed by stacking the vectorized slices from different channels. Matrix rank was then approximately measured through the logarithm-determinant of the covariance matrix. Notably, our filtering technique is applied directly to complex data, avoiding the need to separate magnitude and phase or divide real and imaginary data, thereby ensuring minimal information loss. The degree of low-rank regularization is controlled based on the estimated noise level, striking a balance between noise removal and texture preservation. A noteworthy advantage of our framework is its freedom from parameter tuning, distinguishing it from most existing methods. Experimental results on real-world imaging data demonstrate the effectiveness of our proposed approach in significantly improving ASL perfusion quality. By effectively mitigating noise while preserving important textural information, our method showcases its potential for enhancing the utility and accuracy of ASL perfusion MRI, paving the way for improved neuroimaging studies and clinical diagnoses.

Global brain connectivity: Test-retest stability and association with biological and neurocognitive variables.

BACKGROUND: Global brain connectivity (GBC) enables measuring brain regions' functional connectivity strength at rest by computing the average correlation between each brain voxel's time-series and that of all other voxels. NEW METHOD: We used resting-state fMRI (rs-fMRI) data of young adult participants from the Human Connectome Project (HCP) dataset to explore the test-retest stability of GBC, the brain regions with higher or lower GBC, as well as the associations of this measure with age, sex, and fluid intelligence. GBC was computed by considering separately the positive and negative correlation coefficients (positive GBC and negative GBC). RESULTS: Test-retest stability was higher for positive compared to negative GBC. Areas with higher GBC were located in the default mode network, insula, and visual areas, while regions with lower GBC were in subcortical regions, temporal cortex, and cerebellum. Higher age was related to global reduction of positive GBC. Males displayed higher positive GBC in the whole brain. Fluid intelligence was associated to increased positive GBC in fronto-parietal, occipital and temporal regions. COMPARISON WITH EXISTING METHOD: Compared to previous works, this study adopted a larger sample size and tested GBC stability using data from different rs-fMRI sessions. Moreover, these associations were examined by testing positive and negative GBC separately. CONCLUSIONS: Lower stability for negative compared to positive GBC suggests that negative correlations may reflect less stable couplings between brain regions. Our findings indicate a greater importance of positive compared to negative GBC for the associations of functional connectivity strength with biological and neurocognitive variables.

NADPHnet: a novel strategy to predict compounds for regulation of NADPH metabolism via network-based methods.

Identification of compounds to modulate NADPH metabolism is crucial for understanding complex diseases and developing effective therapies. However, the complex nature of NADPH metabolism poses challenges in achieving this goal. In this study, we proposed a novel strategy named NADPHnet to predict key proteins and drug-target interactions related to NADPH metabolism via network-based methods. Different from traditional approaches only focusing on one single protein, NADPHnet could screen compounds to modulate NADPH metabolism from a comprehensive view. Specifically, NADPHnet identified key proteins involved in regulation of NADPH metabolism using network-based methods, and characterized the impact of natural products on NADPH metabolism using a combined score, NADPH-Score. NADPHnet demonstrated a broader applicability domain and improved accuracy in the external validation set. This approach was further employed along with molecular docking to identify 27 compounds from a natural product library, 6 of which exhibited concentration-dependent changes of cellular NADPH level within 100 µM, with Oxyberberine showing promising effects even at 10 µM. Mechanistic and pathological analyses of Oxyberberine suggest potential novel mechanisms to affect diabetes and cancer. Overall, NADPHnet offers a promising method for prediction of NADPH metabolism modulation and advances drug discovery for complex diseases.

Serum beta2-microglobulin acts as a biomarker for severity and prognosis in glioma patients: a preliminary clinical study.

BACKGROUND: Gliomas are the deadliest malignant tumors of the adult central nervous system. We previously discovered that beta2-microglobulin (B2M) is abnormally upregulated in glioma tissues and that it exerts a range of oncogenic effects. Besides its tissue presence, serum B2M levels serve as biomarkers for various diseases. This study aimed to explore whether serum B2M levels can be used in the diagnosis and prognosis of gliomas. METHODS: Medical records from 246 glioma patients were retrospectively analyzed. The relationship between preoperative serum B2M levels and clinicopathological features was examined. Kaplan-Meier analysis, alongside uni- and multivariate Cox regression, assessed the association between B2M levels, systemic inflammatory markers, and glioma patient prognosis. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic significance of these biomarkers specifically for glioblastoma (GBM). RESULTS: Patients with malignant gliomas exhibited elevated preoperative serum B2M levels. Glioma patients with high serum B2M levels experienced shorter survival times. Multivariate Cox analysis determined the relationship between B2M levels (hazard ratio = 1.92, 95% confidence interval: 1.05-3.50, P = 0.034) and the overall survival of glioma patients. B2M demonstrated superior discriminatory power in distinguishing between GBM and non-GBM compared to inflammation indicators. Moreover, postoperative serum B2M levels were lower than preoperative levels in the majority of glioma patients. CONCLUSIONS: High preoperative serum B2M levels correlated with malignant glioma and a poor prognosis. Serum B2M shows promise as a novel biomarker for predicting patient prognosis and reflecting the therapeutic response.

Highly Regular Layered Structure via Dual-Spatially-Confined Alignment of Nanosheets Enables High-Performance Nanocomposites.

Assembling ultrathin nanosheets into layered structure represents one promising way to fabricate high-performance nanocomposites. However, how to minimize the internal defects of the layered assemblies to fully exploit the intrinsic mechanical superiority of nanosheets remains challenging. Here, a dual-scale spatially confined strategy for the co-assembly of ultrathin nanosheets with different aspect ratios into a near-perfect layered structure is developed. Large-aspect-ratio (LAR) nanosheets are aligned due to the microscale confined space of a flat microfluidic channel, small-aspect-ratio (SAR) nanosheets are aligned due to the nanoscale confined space between adjacent LAR nanosheets. During this co-assembly process, SAR nanosheets can flatten LAR nanosheets, thus reducing wrinkles and pores of the assemblies. Benefiting from the precise alignment (orientation degree of 90.74%) of different-sized nanosheets, efficient stress transfer between nanosheets and interlayer matrix is achieved, resulting in layered nanocomposites with multiscale mechanical enhancement and superior fatigue durability (100 000 bending cycles). The proposed co-assembly strategy can be used to orderly integrate high-quality nanosheets with different sizes or diverse functions toward high-performance or multifunctional nanocomposites.

Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging.

Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Our key findings include: 1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. 2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. 3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information, highlighting their distinct roles in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

Human NMO-IgG Induced Different Pathological and Immunological Changes in the CNS and Peripheral Tissues of Mice.

OBJECTIVES: The majority of neuromyelitis optica spectrum disorders (NMOSD) patients are seropositive for aquaporin-4 (AQP4)-specific antibodies [also named neuromyelitis optica immunoglobulin G antibodies (NMO-IgG)]. Although NMO-IgG can induce pathological changes in the central nervous system (CNS), the immunological changes in the CNS and peripheral tissue remain largely unknown. We investigated whether NMO-IgG binds to tissue expressing AQP4 and induces immunological changes in the peripheral tissue and CNS. METHODS: C57BL/6 female mice were assigned into an NMOSD or control group. Pathological and immunological changes in peripheral tissue and CNS were measured by immunostaining and flow cytometry, respectively. Motor impairment was measured by open-field test. RESULTS: We found that NMO-IgG did bind to astrocyte- and AQP4-expressing peripheral tissue, but induced glial fibrillary acidic protein and AQP4 loss only in the CNS. NMO-IgG induced the activation of microglia and modulated microglia polarization toward the classical (M1) phenotype, but did not affect innate or adaptive immune cells in the peripheral immune system, such as macrophages, neutrophils, Th17/Th1, or IL-10-producing B cells. In addition, NMOSD mice showed significantly less total distance traveled and higher immobility time in the open field. CONCLUSIONS: We found that injection of human NMO-IgG led to astrocytopathic lesions with microglial activation in the CNS. However, there were no significant pathological or immunological changes in the peripheral tissues.

STAT3-induced lncRNA GNAS-AS1 accelerates keloid formation by mediating the miR-196a-5p/CXCL12/STAT3 axis in a feedback loop.

Keloids are pathological scar tissue resulting from skin trauma or spontaneous formation, often accompanied by itching and pain. Although GNAS antisense RNA 1 (GNAS-AS1) shows abnormal upregulation in keloids, the underlying molecular mechanism is unclear. The levels of genes and proteins in clinical tissues from patients with keloids and human keloid fibroblasts (HKFs) were measured using quantitative reverse transcription PCR, western blot and enzyme-linked immunosorbent assay. The features of HKFs, including proliferation and migration, were evaluated using cell counting kit 8 and a wound healing assay. The colocalization of GNAS-AS1 and miR-196a-5p in HKFs was measured using fluorescence in situ hybridization. The relationships among GNAS-AS1, miR-196a-5p and C-X-C motif chemokine ligand 12 (CXCL12) in samples from patients with keloids were analysed by Pearson correlation analysis. Gene interactions were validated by chromatin immunoprecipitation and luciferase reporter assays. GNAS-AS1 and CXCL12 expression were upregulated and miR-196a-5p expression was downregulated in clinical tissues from patients with keloids. GNAS-AS1 knockdown inhibited proliferation, migration, and extracellular matrix (ECM) accumulation of HKFs, all of which were reversed by miR-196a-5p downregulation. Signal transducer and activator of transcription 3 (STAT3) induced GNAS-AS1 transcription through GNAS-AS1 promoter interaction, and niclosamide, a STAT3 inhibitor, decreased GNAS-AS1 expression. GNAS-AS1 positively regulated CXCL12 by sponging miR-196-5p. Furthermore, CXCL12 knockdown restrained STAT3 phosphorylation in HKFs. Our findings revealed a feedback loop of STAT3/GNAS-AS1/miR-196a-5p/CXCL12/STAT3 that promoted HKF proliferation, migration and ECM accumulation and affected keloid progression.

Stable and wavelength-tunable multiwavelength laser for high-rate measurement device independent quantum key distribution.

Measurement device independent quantum key distribution (MDI QKD) has attracted growing attention for its immunity to attacks at the measurement unit, but its unique structure limits the secret key rate. Utilizing the wavelength division multiplexing (WDM) technique and reducing error rates are effective strategies for enhancing the secret key rate. Reducing error rates often requires active feedback control of wavelengths using precise external references. However, for a multiwavelength laser, employing multiple references to stabilize each wavelength output places stringent demands on these references and significantly increases system complexity. Here, we demonstrate a stable, wavelength-tunable multiwavelength laser with an output wavelength ranging from 1270 to 1610 nm. Through precise temperature control and stable drive current, we passively lock the laser wavelength, achieving remarkable wavelength stability. This significantly reduce the error rate, leading to an almost doubling of the secret key rate compared to previous experiments. Furthermore, the exceptional wavelength stability offered by our multiwavelength laser, combined with the WDM technique, has further boosted the secret key rate of MDI QKD. With a wide wavelength tuning range of 5.1 nm, our multiwavelength laser facilitates flexible operation across multiple dense wavelength division multiplexing channels. Coupled with high wavelength stability and multiple wavelength outputs simultaneously, this laser offers a promising solution for a high-rate MDI QKD system.