Ketamine induces insomnia-like symptom of zebrafish at environmentally relevant concentrations by mediating GABAergic synapse.

Although the stimulative effects on the normal behaviors of fish posed by ketamine (KET) were well-studied, the adverse effects on the behavioral functions induced by KET at nighttime were unknown. Here, we used zebrafish larvae as a model exposed to KET (10, 50, 100, and 250 ng/L) at environmental levels for 21 days. The behavioral functions at nighttime, morphological changes during exposure stage, and alterations on the associated genes transcriptional levels of fish were determined. The difficultly initiating sleep was found in the fish exposed to KET, while the sleep duration of the animals was at the normal levels in exposure groups. The significant suppressions of the developmentally relevant genes, including bmp2, bmp4, and pth2ra were consistent with the developmental abnormalities of fish found in exposure groups. Moreover, the expression of γ-aminobutyric acid (GABA) receptor increased and melatonin (MTN) receptor decreased while the levels of GABA and MTN remained unchanged after exposure, by gene expression analysis and molecular docking. In addition, the transcriptional expression of apoptotic genes, including tp53, aifm1, and casp6, was significantly upregulated by KET. After a 7-day recovery, the insomnia-like behaviors (shorter sleep duration) were observed in zebrafish from the 250 ng/L-KET group. Accordingly, the adverse outcome pathway framework of KET was constructed by prognostic assessment of zebrafish larvae. This study suggested that the adverse outcomes of KET on the sleep health of organisms at environmentally relevant concentrations should be concerned.

Combining T1rho and advanced diffusion MRI for noninvasively staging liver fibrosis: an experimental study in rats.

PURPOSE: To investigate the value of imaging parameters derived from T1 relaxation times in the rotating frame (T1ρ or T1rho), diffusion kurtosis imaging (DKI) and intravoxel incoherent motion (IVIM) in assessment of liver fibrosis in rats and propose an optimal diagnostic model based on multiparametric MRI. METHODS: Thirty rats were divided into one control group and four fibrosis experimental groups (n = 6 for each group). Liver fibrosis was induced by administering thioacetamide (TAA) for 2, 4, 6, and 8 weeks. T1ρ, mean kurtosis (MK), mean diffusivity (MD), perfusion fraction (f), true diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were measured and compared among different fibrosis stages. An optimal diagnostic model was established and the diagnostic efficiency was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The mean AUC values, sensitivity, and specificity of T1ρ and MD derived from DKI across all liver fibrosis stages were comparable but much higher than those of other imaging parameters (0.954, 92.46, 91.85 for T1ρ; 0.949, 92.52, 91.24 for MD). The model combining T1ρ and MD exhibited better diagnostic performance with higher AUC values than any individual method for staging liver fibrosis (≥ F1: 1.000 (0.884-1.000); ≥ F2: 0.935 (0.782-0.992); ≥ F3: 0.982 (0.852-1.000); F4: 0.986 (0.859-1.000)). CONCLUSION: Among the evaluated imaging parameters, T1ρ and MD were superior for differentiating varying liver fibrosis stages. The model combining T1ρ and MD was promising to be a credible diagnostic biomarker to detect and accurately stage liver fibrosis.

Salvia miltiorrhiza ameliorates endometritis in dairy cows by relieving inflammation, energy deficiency and blood stasis.

Introduction: According to traditional Chinese veterinary medicine, endometritis is caused by a combination of Qi deficiency, blood stasis, and external evil invasion. Salvia miltiorrhiza is a traditional Chinese medicine that counteracts blood stasis and has additional demonstrated effects in boosting energy and restraining inflammation. Salvia miltiorrhiza has been employed in many traditional Chinese prescriptions that have proven effective in healing clinical dairy cow endometritis. Methods: the in vivo effect of Salvia miltiorrhiza in treating endometritis was evaluated in dairy cows. In addition, bovine endometrial epithelium cell inflammation and rat blood stasis models were employed to demonstrate the crosstalk between energy, blood circulation and inflammation. Network analysis, western blotting, qRT-PCR and ELISA were performed to investigate the molecular mechanism of Salvia miltiorrhiza in endometritis treatment. Results: The results demonstrate that treatment with Salvia miltiorrhiza relieves uterine inflammation, increases blood ATP concentrations, and prolongs blood clotting times. Four of the six Salvia miltiorrhiza main components (SMMCs) (tanshinone IIA, cryptotanshinone, salvianolic acid A and salvianolic acid B) were effective in reversing decreased ATP and increased IL-1ß, IL-6, and IL-8 levels in an in vitro endometritis model, indicating their abilities to ameliorate the negative energy balance and external evil invasion effects of endometritis. Furthermore, in a blood stasis rat model, inflammatory responses were induced in the absence of external infection; and all six SMMCs inhibited thrombin-induced platelet aggregation. Network analysis of SMMC targets predicted that Salvia miltiorrhiza may mediate anti-inflammation via the Toll-like receptor signaling pathway; anti-aggregation via the Platelet activation pathway; and energy balance via the Thermogenesis and AMPK signaling pathways. Multiple molecular targets within these pathways were verified to be inhibited by SMMCs, including P38/ERK-AP1, a key molecular signal that may mediate the crosstalk between inflammation, energy deficiency and blood stasis. Conclusion: These results provide mechanistic understanding of the therapeutic effect of Salvia miltiorrhiza for endometritis achieved through Qi deficiency, blood stasis, and external evil invasion.

Nanoparticle drug delivery systems responsive to tumor microenvironment: Promising alternatives in the treatment of triple-negative breast cancer.

The conventional therapeutic treatment of triple-negative breast cancer (TNBC) is negatively influenced by the development of tumor cell drug resistant, and systemic toxicity of therapeutic agents due to off-target activity. In accordance with research findings, nanoparticles (NPs) responsive to the tumor microenvironment (TME) have been discovered for providing opportunities to selectively target tumor cells via active targeting or Enhanced Permeability and Retention (EPR) effect. The combination of the TME control and therapeutic NPs offers promising solutions for improving the prognosis of the TNBC because the TME actively participates in tumor growth, metastasis, and drug resistance. The NP-based systems leverage stimulus-responsive mechanisms, such as low pH value, hypoxic, excessive secretion enzyme, concentration of glutathione (GSH)/reactive oxygen species (ROS), and high concentration of Adenosine triphosphate (ATP) to combat TNBC progression. Concurrently, NP-based stimulus-responsive introduces a novel approach for drug dosage design, administration, and modification of the pharmacokinetics of conventional chemotherapy and immunotherapy drugs. This review provides a comprehensive examination of the strengths, limitations, applications, perspectives, and future expectations of both novel and traditional stimulus-responsive NP-based drug delivery systems for improving outcomes in the medical practice of TNBC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

A multi-omics investigation of the lung injury induced by PM2.5 at environmental levels via the lung-gut axis.

Long-term exposure to fine particulate matter (PM2.5) posed injury for gastrointestinal and respiratory systems, ascribing with the lung-gut axis. However, the cross-talk mechanisms remain unclear. Here, we attempted to establish the response networks of lung-gut axis in mice exposed to PM2.5 at environmental levels. Male Balb/c mice were exposed to PM2.5 (dose of 0.1, 0.5, and 1.0 mg/kg) collected from Chengdu, China for 10 weeks, through intratracheally instillation, and examined the effect of PM2.5 on lung functions of mice. The changes of lung and gut microbiota and metabolic profiles of mice in different groups were determined. Furthermore, the results of multi-omics were conjointly analyzed to elucidate the primary microbes and the associated metabolites in lung and gut responsible for PM2.5 exposure. Accordingly, the cross-talk network and key pathways between lung-gut axis were established. The results indicated that exposed to PM2.5 0.1 mg/kg induced obvious inflammations in mice lung, while emphysema was observed at 1.0 mg/kg. The levels of metabolites guanosine, hypoxanthine, and hepoxilin B3 increased in the lung might contribute to lung inflammations in exposure groups. For microbiotas in lung, PM2.5 exposure significantly declined the proportions of Halomonas and Lactobacillus. Meanwhile, the metabolites in gut including L-tryptophan, serotonin, and spermidine were up-regulated in exposure groups, which were linked to the decreasing of Oscillospira and Helicobacter in gut. Via lung-gut axis, the activations of pathways including Tryptophan metabolism, ABC transporters, Serotonergic synapse, and Linoleic acid metabolism contributed to the cross-talk between lung and gut tissues of mice mediated by PM2.5. In summary, the microbes including Lactobacillus, Oscillospira, and Parabacteroides, and metabolites including hepoxilin B3, guanosine, hypoxanthine, L-tryptophan, and spermidine were the main drivers. In this lung-gut axis study, we elucidated some pro- and pre-biotics in lung and gut microenvironments contributed to the adverse effects on lung functions induced by PM2.5 exposure.

Numerical investigation of quantitative pulmonary pressure ratio in different degrees of stenosis.

BACKGROUND: Pulmonary artery stenosis endangers people's health. Quantitative pulmonary pressure ratio (QPPR) is very important for clinicians to quickly diagnose diseases and develop treatment plans. OBJECTIVE: Our purpose of this paper is to investigate the effects of different degrees (50% and 80%) of pulmonary artery stenosis on QPPR. METHODS: An idealized model is established based on the normal size of human pulmonary artery. The hemodynamic governing equations are solved using fluid-structure interaction. RESULTS: The results show that the QPPR decreases with the increase of stenosis degree, and it is closely related to the pressure drop at both ends of stenosis. Blood flow velocity and wall shear stress are sensitive to the stenosis degree. When the degree of stenosis is 80%, the amplitude of changes of blood flow velocity and wall shear stress at both ends of stenosis is lower. CONCLUSIONS: The results suggest that the degree of pulmonary artery stenosis has a significant impact on QPPR and hemodynamic changes. This study lays a theoretical foundation for further study of QPPR.

SOCS5-RBMX stimulates SREBP1-mediated lipogenesis to promote metastasis in steatotic HCC with HBV-related cirrhosis.

Abnormal lipid metabolism promotes hepatocellular carcinoma (HCC) progression, which engenders therapeutic difficulties owing to unclear mechanisms of the phenomenon. We precisely described a special steatotic HCC subtype with HBV-related cirrhosis and probed its drivers. Hematoxylin-eosin (HE) staining of 245 HCC samples revealed a special HCC subtype (41 cases) characterized by HBV-related cirrhosis and intratumoral steatosis without fatty liver background, defined as steatotic HCC with HBV-related cirrhosis (SBC-HCC). SBC-HCC exhibits a larger tumor volume and worse prognosis than non-SBC-HCC. Screening for driver genes promoting fatty acid (FA) biosynthesis in the Gao's HBV-related cirrhosis HCC cases and GSE121248' HBV-related HCC cases revealed that high expression of SOCS5 predicts increased FA synthesis and that SOCS5 is upregulated in SBC-HCC. Through proteomics, metabolomics, and both in vivo and in vitro experiments, we demonstrated that SOCS5 induces lipid accumulation to promote HCC metastasis. Mechanistically, through co-IP and GST-pulldown experiments, we found that the SOCS5-SH2 domain, especially the amino acids Y413 and D443, act as critical binding sites for the RBMX-RRM domain. SOCS5-RBMX costimulates the promoter of SREBP1, inducing de novo lipogenesis, while mutations in the SH2 domain, Y413, and D443 reverse this effect. These findings precisely identified SBC-HCC as a special steatotic HCC subtype and highlighted a new mechanism by which SOCS5 promotes SBC-HCC metastasis.

DIA-Based Proteomic Analysis Reveals MYOZ2 as a Key Protein Affecting Muscle Growth and Development in Hybrid Sheep.

Hybridization of livestock can be used to improve varieties, and different hybrid combinations produce unique breeding effects. In this study, male Southdown and Suffolk sheep were selected to hybridize with female Hu sheep to explore the effects of male parentage on muscle growth and the development of offspring. Using data-independent acquisition technology, we identified 119, 187, and 26 differentially abundant proteins (DAPs) between Hu × Hu (HH) versus Southdown × Hu (NH), HH versus Suffolk × Hu (SH), and NH versus SH crosses. Two DAPs, MYOZ2 and MYOM3, were common to the three hybrid groups and were mainly enriched in muscle growth and development-related pathways. At the myoblast proliferation stage, MYOZ2 expression decreased cell viability and inhibited proliferation. At the myoblast differentiation stage, MYOZ2 expression promoted myoblast fusion and enhanced the level of cell fusion. These findings provide new insights into the key proteins and metabolic pathways involved in the effect of male parentage on muscle growth and the development of hybrid offspring in sheep.

A hemodynamic model of artery bypass graft considering microcirculation function.

BACKGROUND: The incidence of arterial stenosis is increasing year by year. In order to better diagnose and treat arterial stenosis, numerical simulation technology has become a popular method. OBJECTIVE: A novel model is constructed to investigate the influence of microcirculation on the hemodynamics of artery bypass graft. METHODS: In this paper, a severely narrow artery bypass graft model is considered. The geometric shape includes a narrow artery tube and a bypass graft of the same diameter with a 45° suture angle. The fluid-structure interaction model is considered by finite element numerical calculation, and the flow is simulated with microcirculation as the outlet boundary condition. The changes of blood flow velocity, pressure and wall shear stress are analyzed. RESULTS: The results show that blood almost entirely flows into the graft tube and there is no recirculation area at the anastomosis. CONCLUSION: The artery bypass graft model considering microcirculation function could simulate the physiological characteristics of blood flow more reasonably, and it provide helps for clinicians to diagnose and treat arterial stenosis.

Intracranial hemorrhage risk in patients with cerebral microbleeds after mechanical thrombectomy for acute ischemic stroke: a systematic review and meta-analysis.

Background and purpose intracranial hemorrhage risk in patients with cerebral microbleeds (CMBs) after mechanical thrombectomy for acute ischemic stroke (AIS) was investigated. We searched PubMed and Embase from inception to 29 August 2023 for relevant studies, calculated pooled odds ratio (ORs) of intracerebral hemorrhage (ICH) subtypes in AIS patients with CMB presence, 1-4 or ≥ 5 CMBs versus CMB absence, and with different CMB locations after mechanical thrombectomy. ICH subtypes included any ICH, symptomatic and asymptomatic ICH, hemorrhage outside infarct (including subarachnoid hemorrhage), hemorrhagic infarction, and parenchymal hemorrhage after mechanical thrombectomy. Five eligible studies enrolling 2051 patients were included. No significant association was shown between CMB locations (lobar, deep, infratentorial or mixed) and ICH risk. CMB presence or 1-4 CMBs did not significantly increase the risk of any ICH, symptomatic or asymptomatic ICH, ICH outside infarct, subarachnoid hemorrhage, hemorrhagic infarction, or parenchymal hemorrhage. CMBs ≥ 5 increased the risk of any ICH (OR 2.58, 95% CI 1.16-5.72), parenchymal hemorrhage (OR 3.38, 95% CI 1.43-7.97) and parenchymal hemorrhage-2 (OR 5.33, 2.05-13.86), without increasing hemorrhagic infarction or parenchymal haemorrhage-1 risk. After adjusted for possible confounding factors, increases in CMB burden were associated with hemorrhagic complications but not with symptomatic ICH. In AIS patients who received mechanical thrombectomy, no association was shown between CMB location and ICH risk. ICH risk was not significantly increased by CMB presence or 1-4 CMBs. ICH risk in patients with ≥ 5 CMBs requires further study.

Single-nucleus RNA sequencing reveals that macrophages and smooth muscle cells promote carotid atherosclerosis progression through mitochondrial autophagy.

Carotid atherosclerotic plaques are the manifestation of atherosclerosis in the carotid arteries and can significantly increase the incidence of cerebrovascular disease. Macrophages and smooth muscle cells are crucial for their development. To reveal the mechanism of carotid atherosclerotic plaque formation, we performed single-nucleus RNA sequencing of the carotid plaque tissue and identified 11 cell types, and the macrophages were divided into 5 different macrophage subpopulations. The macrophages and smooth muscle cells in the patients with symptomatic carotid atherosclerotic plaques caused intraplaque cell death via the mitochondrial autophagic pathway, resulting in plaque instability and rupture, which in turn led to clinical cardiovascular and cerebrovascular events. The findings provide new insights into carotid atherosclerosis formation, and this may provide new directions for the prevention and treatment of carotid atherosclerosis.

Prognostic value of platelet-to-lymphocyte ratio in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization and tyrosine kinase inhibitors plus immune checkpoints inhibitors.

Purpose: To investigate the prognostic value of platelet-to-lymphocyte ratio (PLR) in patients with unresectable hepatocellular carcinoma (uHCC) treated with transarterial chemoembolization (TACE) and tailored tyrosine kinase inhibitors (TKIs) plus immune checkpoints inhibitors (ICIs). Materials and methods: Ninety-eight patients from May 2018 to January 2022 in our hospital were enrolled in this study. The receiver operating characteristic (ROC) curve analysis was performed and the corresponding Youden index was used to determine the optimal PLR cut-off. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of patients were evaluated based on the PLR cut-off. The factors affecting survival were assessed using univariate and multivariate Cox proportional hazards regression analyses. Results: The PLR cut-off was 98.89. There were 49 patients in the low pretreatment PLR group (PLR ≤ 98.89) and 49 patients in the high PLR group (PLR > 98.89). Patients with low pretreatment PLR had significantly longer median OS (25.7 months vs 16.1 months; P < 0.001) and PFS (14.9 months vs 10.2 months; P < 0.001) than those with high pretreatment PLR. The multivariate analysis revealed that ALT, tumor size, and PLR are risk factors affecting OS. The three independent factors affecting PFS are tumor size, AFP, and PLR. The AEs were tolerable and manageable. Conclusion: The low pretreatment PLR (PLR ≤ 98.89) was an independent protective factor for the survival outcomes of patients in this study. PLR was helpful for clinicians to predict the prognosis and identify the patients with uHCC who were most likely to benefit from TACE + TKIs + ICIs.

Development of Zn2+-controlled expression system for lactic acid bacteria and its application in engineered probiotics.

Lactococcus lactis and Streptococcus thermophilus are considered as ideal chassis of engineered probiotics, while food-grade genetic tools are limited in those strains. Here, a Zn2+-controlled gene expression (ZICE) system was identified in the genome of S. thermophilus CGMCC7.179, including a transcriptional regulator sczAst and a promoter region of cation transporter czcD (PczcDst). Specific binding of the SczAst to the palindromic sequences in PczcDst was demonstrated by EMSA analysis, suggesting the regulation role of SczAst on PczcDst. To evaluate their possibility to control gene expression in vivo, the sczAst-PczcDst was employed to drive the expression of green fluorescence protein (GFP) gene in L. lactis NZ9000 and S. thermophilus CGMCC7.179, respectively. Both of the transformants could express GFP under Zn2+ induction, while no fluorescence without Zn2+ addition. For optimal conditions, Zn2+ was used at a final concentration of 0.8 mM in L. lactis and 0.16 mM in S. thermophilus at OD600 close to 0.4, and omitting yeast extract powder in the medium unexpectedly improved GFP expression level by 2.2-fold. With the help of the ZICE system, engineered L. lactis and S. thermophilus strains were constructed to secret cytokine interleukin-10 (IL-10) with immunogenicity, and the IL-10 content in the supernatant of the engineered L. lactis was 59.37 % of that under the nisin controlled expression system. This study provided a tightly controlled expression system by the food-grade inducer Zn2+, having potential in development of engineered probiotics.

[Establishment of a 21-color Panel for the Detection of Immune Cell Subsets 
in Human Non-small Cell Lung Cancer Tumor Tissues with Flow Cytometry].

BACKGROUND: With the rise of multicolor flow cytometry, flow cytometry has become an important means to detect the immune microenvironment of lung cancer, but most of them are used to detect the proportion of cell subsets or the function of major cell subsets, and they cannot be detected at the same time. Therefore, a reliable 21-color flow cytometry protocol was established to detect the immune cell subsets in human non-small cell lung cancer (NSCLC) tumor tissues. METHODS: Cell membrane surface antibodies cluster of differentiation (CD)45, CD3, CD19, CD4, CD8, programmed cell death 1 (PD-1), CD39, CD103, CD25, CD127, chemokine receptor 8 (CCR8), CD56, CD11c, human leukocyte antigen (HLA)-DR, CD38, CD27, CD69, CD62L, CD45RA, CCR7 and nucleic acid dye L/D were used to develop the protocol. Firstly, antibody titration experiments, voltage optimization, subtraction of one color staining and single color staining experiments were carried out for each antibody, and after the experimental conditions and detection schemes were determined, the feasibility of the scheme was verified by using peripheral blood mononuclear cells (PBMCs) specimens of six healthy adult volunteers. Tumor tissue samples from 6 NSCLC patients were tested and analyzed. RESULTS: The established 21-color flow cytometry protocol was used to detect the tumor tissue samples of 6 NSCLC patients, and the proportion of each cell subset in lung cancer tissue, as well as the immunophenotype and differentiation of the main cell population, were analyzed. CONCLUSIONS: The successfully established 21-color flow cytometry protocol is suitable for the detection of PBMCs and NSCLC tissue samples, which provides an effective new idea for monitoring the immune microenvironment status in lung cancer.

Is the frequency of imaging markers still a predictor for revised intracerebral hemorrhage expansion?

INTRODUCTION: Frequency of imaging markers (FIM) has been described as a novel predictor for hematoma expansion after intracerebral hemorrhage (ICH). A revised definition of hematoma expansion that incorporates intraventricular hemorrhage (IVH) growth, that is, revised hematoma expansion (RHE), has also been proposed. Nevertheless, the associations between FIM and IVH growth or RHE remains unexplored. The objective of this study was to assess the influence and performance of the FIM on two types. MATERIALS AND METHODS: Patient selection and variables were based on our published protocol. FIM was defined as the ratio of the number of imaging markers to the onset-to-neuroimaging time. The association between FIM and two definitions was tested by multivariate analysis. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the FIM on two definitions were also evaluated. RESULTS: There were 303 (20.36%) and 583 (39.18%) subjects in the IVH growth and RHE, respectively. Multivariate analysis demonstrated that FIM was associated with both IVH growth and RHE (odds ratio [OR] = 1.96, 95% confidence interval [CI] = 1.60-2.39; OR = 15.01, 95% CI = 10.51-21.43, respectively). The optimal cutoff points for FIM to predict IVH growth and RHE were 0.63 and 0.62, with AUC, sensitivity, specificity, PPV, and NPV of 0.66, 0.50, 0.78, 0.36, and 0.86 versus 0.80, 0.60, 0.93, 0.84, and 0.78, respectively. DISCUSSION AND CONCLUSION: FIM was not only a predictor of IVH growth, but also of RHE. These findings may have important clinical implications for decision-making based on risk stratification of patients with ICH.

Genome-wide detection of structural variation in some sheep breeds using whole-genome long-read sequencing data.

Genomic structural variants (SVs) constitute a significant proportion of genetic variation in the genome. The rapid development of long-reads sequencing has facilitated the detection of long-fragment SVs. There is no published study to detect SVs using long-read data from sheep. We applied a long-read mapping approach to detect SVs and characterized a total of 30,771 insertions, deletions, inversions and translocations. We identified 716, 916, 842 and 303 specific SVs in Southdown sheep, Alpine merino sheep, Qilian White Tibetan sheep and Oula sheep, respectively. We annotated these SVs and found that these SV-related genes were primarily enriched in the well-established pathways involved in the regulation of the immune system, growth and development and environmental adaptability. We detected and annotated SVs based on NGS resequencing data to validate the accuracy based on third-generation detection. Moreover, five candidate SVs were verified using the PCR method in 50 sheep. Our study is the first to use a long-reads sequencing approach to construct a novel structural variation map in sheep. We have completed a preliminary exploration of the potential effects of SVs on sheep.

High-sensitivity hybrid MoSe2/AgInGaS quantum dot heterojunction photodetector.

Zero-dimensional (0D)-two-dimensional (2D) hybrid photodetectors have received widespread attention due to their outstanding photoelectric performances. However, these devices with high performances mainly employ quantum dots that contain toxic elements as sensitizing layers, which restricts their practical applications. In this work, we used eco-friendly AgInGaS quantum dots (AIGS-QDs) as a highly light-absorbing layer and molybdenum diselenide (MoSe2) as a charge transfer layer to construct a 0D-2D hybrid photodetector. Notably, we observed that MoSe2 strongly quenches the photoluminescence (PL) of AIGS-QDs and decreases the decay time of PL in the MoSe2/AIGS-QDs heterojunction. The MoSe2/AIGS-QDs hybrid photodetector demonstrates a responsivity of 14.3 A W-1 and a high detectivity of 6.4 × 1011 Jones. Moreover, the detectivity of the hybrid phototransistor is significantly enhanced by more than three times compared with that of the MoSe2 photodetector. Our work suggests that 0D-2D hybrid photodetectors with multiplex I-III-VI QDs provide promising potential for future high-sensitivity photodetectors.

Cancer-associated fibroblast-derived extracellular vesicles promote lymph node metastases in oral cavity squamous cell carcinoma by encapsulating ITGB1 and BMI1.

BACKGROUND: Extracellular vesicles (EVs) have been revealed to facilitate the development of oral squamous cavity cell carcinoma (OCSCC), while its supporting role in lymph node metastases is under continuous investigation. This study aimed to examine the function of cancer-associated fibroblasts (CAF)-derived EVs (CAF-EVs) during lymph node metastasis in OCSCC and the mechanisms. METHODS: CAF were isolated from OCSCC tissues of patients, and CAF-EVs were extracted and identified. EdU, colony formation, wound healing, and Transwell assays were performed. The OCSCC cells before and after CAF-EVs treatment were injected into mice to probe the effects of CAF-EVs on tumor growth and lymph node metastasis, respectively. The effect of CAF-EVs treatment on transcriptome changes in OCSCC cells was analyzed. Clinical data of patients with OCSCC were analyzed to determine the prognostic significance of the selected genes. Finally, loss-of-function assays were conducted to corroborate the involvement of polycomb complex protein BMI-1 (BMI1) and integrin beta1 (ITGB1). RESULTS: CAF-EVs promoted the malignant behavior of OCSCC cells and accelerated tumor growth and lymph node metastasis in mice. CAF-EVs significantly increased the expression of BMI1 and ITGB1, and the expression of BMI1 and ITGB1 was negatively correlated with the overall survival and relapse-free survival of OCSCC patients. Knockdown of BMI1 or ITGB1 in OCSCC cells abated the promoting effects of CAF-EVs in vitro and in vivo. CONCLUSION: CAF-EVs elicited the metastasis-promoting properties in OCSCC by elevating BMI1 and ITGB1, suggesting that BMI1 and ITGB1 could be potential biomarkers and therapeutic targets for OCSCC.

Electrochemically Mediated Surface-Initiated Atom Transfer Radical Polymerization by ppm of CuII/Tris(2-pyridylmethyl)amine.

Atom transfer radical polymerization (ATRP) is one of the most widely used methods for modifying surfaces with functional polymer films and has received considerable attention in recent years. Here, we report an electrochemically mediated surface-initiated ATRP to graft polymer brushes onto solid substrates catalyzed by ppm amounts of CuII/TPMA in water/MeOH solution. We systematically investigated the type and concentrations of copper/ligand and applied potentials correlated to the polymerization kinetics and polymer brush thickness. Gradient polymer brushes and various types of polymer brushes are prepared. Block copolymerization of 2-hydroxyethyl methacrylate (HEMA) and 3-sulfopropyl methacrylate potassium salt (PSPMA) (poly(HEMA-b-SPMA)) with ultralow ppm eATRP indicates the remarkable preservation of chain end functionality and a pronounced "living" characteristic feature of ppm-level eATRP in aqueous solution for surface polymerization.