Mobile recognition and positioning for multiple visible light communication cells using a convolutional neural network: publisher's note.

This publisher's note contains a correction to Opt. Lett.48, 6468 (2024)10.1364/OL.503007.

Tribological Effects of Quaternary Ammonium-Functionalized Montmorillonite as Water-Based Additives.

In this study, a water-soluble quaternary ammonium salt (QAS)-functionalized montmorillonite (MMT) was fabricated using a mechanochemical method as a high-performance water lubrication additive. The intercalation of QAS into the MMT layer expands the layer spacing of MMT, but does not affect the hydrophilicity of MMT. The ultrathin layer QAS-functionalized montmorillonite (QAS-MMT) demonstrated excellent water-stable dispersion and can be used as a water-based lubrication additive. Only 0.1% addition can reduce the friction coefficient by more than 71.4% and the wear volume by about 58.8% when compared to water, demonstrating its excellent friction reduction and antiwear performance. The frictional mechanism indicates that the physical adsorption film, together with the chemical reaction film, endows the QAS-MMT additives with outstanding tribological performance, provides excellent lubrication for the contact of steel/steel pairs, and prevents the steel surface from being further worn.

LED lighting area recognition for visible light positioning based on convolutional neural network in the industrial internet of things.

In the industrial environment, the positioning of mobile terminals plays an important role in production scheduling. Visible light positioning (VLP) based on a CMOS image sensor has been widely considered as a promising indoor positioning technology. However, the existing VLP technology still faces many challenges, such as modulation and decoding schemes, and strict synchronization requirements. In this paper, a visible light area recognition framework based on convolutional neural network (CNN) is proposed, where the training data is the LED images acquired by the image sensor. The mobile terminal positioning can be realized from the perspective of recognition without modulating LED. The experimental results show that the mean accuracy of the optimal CNN model is as high as 100% for the two-class and the four-class area recognitions, and is more than 95% for the eight-class area recognition. These results are obviously superior to other traditional recognition algorithms. More importantly, the model has high robustness and universality, which can be applied to various types of LED lights.

Visible light sensing based on shadow features using multi-scale region convolutional neural network.

There are various production items in the industrial internet of things (IIoT) environment, such as pedestrians, robots, automated automated guided vehicles, etc. The practice industrial environment requires simultaneous communication and sensing of production items to achieve intelligent production and control. Thus, sensing methods not only require the integration of communication but also achieve sensing tasks such as recognition and positioning. Compared with traditional sensing media, visible light sensing has the advantages of high-speed communication, high sensing accuracy, and security, low energy consumption, and has become a potential sensing technology. Based on the strong directivity of visible light spatial radiation and the consistency of light intensity and position, this paper proposes a multi-scale visible light sensing-region convolutional neural network (VLS-RCNN) framework based on shadow features for multiple target sensing. The framework enables the recognition and positioning to use shared visible light shadow features to assist each other, and the multi-scale compensation strategy of the shadow region makes the framework more robust. The simulation results show that positioning results in the sensing area improve the recognition accuracy. The recognition results also reduce the positioning error without additional overhead. Therefore, this paper provides a new perspective for the sensing technology in the future IIoT, which should be considered to sense objects of interest by utilizing the inherent characteristics of visible light.

Mobile recognition and positioning for multiple visible light communication cells using a convolutional neural network.

The industrial Internet of Things (IIoT) environment involves multiple production items, such as robots and automated guided vehicles (AGVs), among others. The practical industrial scenario requires communication of production items while also considering mobile recognition and positioning. Hence the perception approach requires not only combining communications but also realizing the recognition and positioning of multiple communication cells. This Letter proposes a multi-optical cell recognition and positioning framework based on LED image features. The LED images are obtained by a CMOS image sensor. This framework utilizes convolutional neural networks (CNN) to train LED images for recognition between multiple optical cells and locates precise positions through region recognition within the optical cells. The experimental results show that the mean accuracy of the CNN model for two LED cells is above 99%, and the mean accuracy of region recognition within the optical cell is as high as 100%, which is significantly better than other traditional recognition algorithms. Therefore, the proposed framework can provide location-aware services for visible light communication and has a wide application prospect in IIoT.

LncRNA Airn maintains LSEC differentiation to alleviate liver fibrosis via the KLF2-eNOS-sGC pathway.

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases. The dysregulation of liver sinusoidal endothelial cell (LSEC) phenotype is a critical early event in the fibrotic process. However, the biological function of lncRNAs in LSEC still remains unclear. METHODS: The expression level of lncRNA Airn was evaluated in both human fibrotic livers and serums, as well as mouse fibrotic livers. Gain- and loss-of-function experiments were performed to detect the effect of Airn on LSEC differentiation and hepatic stellate cell (HSC) activation in liver fibrosis. Furthermore, RIP, RNA pull-down-immunoblotting, and ChIP experiments were performed to explore the underlying mechanisms of Airn. RESULTS: We have identified Airn was significantly upregulated in liver tissues and LSEC of carbon tetrachloride (CCl4)-induced liver fibrosis mouse model. Moreover, the expression of AIRN in fibrotic human liver tissues and serums was remarkably increased compared with healthy controls. In vivo studies showed that Airn deficiency aggravated CCl4- and bile duct ligation (BDL)-induced liver fibrosis, while Airn over-expression by AAV8 alleviated CCl4-induced liver fibrosis. Furthermore, we revealed that Airn maintained LSEC differentiation in vivo and in vitro. Additionally, Airn inhibited HSC activation indirectly by regulating LSEC differentiation and promoted hepatocyte (HC) proliferation by increasing paracrine secretion of Wnt2a and HGF from LSEC. Mechanistically, Airn interacted with EZH2 to maintain LSEC differentiation through KLF2-eNOS-sGC pathway, thereby maintaining HSC quiescence and promoting HC proliferation. CONCLUSIONS: Our work identified that Airn is beneficial to liver fibrosis by maintaining LSEC differentiation and might be a serum biomarker for liver fibrogenesis.

YAP/STAT3 promotes the immune escape of larynx carcinoma by activating VEGFR1-TGFß signaling to facilitate PD-L1 expression in M2-like TAMs.

Larynx carcinoma (LC) is the most prevalent head and neck cancer among adults. LC xenograft mouse model was generated to verify the effect of VEGF on macrophage polarization and tumor growth in vivo. EdU assay was performed to measure the cell proliferation. Transwell assay was applied to assess cell migration. The expression of YAP and STAT3 was also significantly increased in LC tumor tissues. Moreover, both YAP and STAT3 overexpression in LC cells promoted the proliferation, migration, as well as the secretion of PD-L1 in M2-like TAMs. Mechanistically, the interaction between YAP and STAT3 facilitated the transcription of VEGF. Moreover, with a co-culture system, VEGF secretion in LC cells enhanced PD-L1 expression in M2-like TAMs via activating VEGFR1-TGFß signaling pathway. Furthermore, VEGF secreted from LC cells also promoted the tumor growth of LC in vivo. We revealed that dysregulated YAP/STAT3 activity in LC cells could enhance the secretion of VEGF, which then functioned on M2-like TAMs via activating VEGFR1-TGFßß pathway to promote the expression of PD-L1 and immunosuppressive function of M2-like TAMs. Therefore, VEGF and PD-L1 might have a pivotal crosstalk between M2-like TAMs and LC cells, which provided a novel therapeutic target in regulating the metastasis of LC in future.

LncRNA-Airn alleviates acute liver injury by inhibiting hepatocyte apoptosis via the NF-κB signaling pathway.

Acute liver injury is a common and serious syndrome caused by multiple factors and unclear pathogenesis. If the injury persists, liver injury can lead to cirrhosis and liver failure and ultimately results in the development of liver cancer. Emerging evidence has indicated that long noncoding RNAs (lncRNAs) play an important role in the development of liver injury. However, the role of antisense Igf2r RNA (Airn) in acute liver injury and its underlying mechanism remain largely unclear. In this study, we show that Airn is upregulated in liver tissue and primary hepatocytes from an acute liver injury mouse model. Consistently, Airn is also overexpressed in serum samples of patients with acute-on-chronic liver failure and is negatively correlated with the Model for End-Stage Liver Disease (MELD) score. Moreover, gene knockout and rescue assays reveal that Airn alleviates CCl 4-induced liver injury by inhibiting hepatocyte apoptosis and oxidative stress in vivo. Further investigation reveals that Airn decreases H 2O 2-induced hepatocyte apoptosis in vitro. Mechanistically, we reveal that Airn represses CCl 4- and H 2O 2-induced enhancement of phosphorylation of p65 and IκBα, suggesting that Airn inhibits hepatocyte apoptosis by inactivating the NF-κB pathway. In conclusion, our results demonstrate that Airn can alleviate acute liver injury by inhibiting hepatocyte apoptosis via inactivating the NF-κB signaling pathway, and Airn could be a potential biomarker for acute liver injury.

HOTAIRM1 promotes osteogenic differentiation and alleviates osteoclast differentiation by inactivating the NF-κB pathway.

Osteoporosis (OP), one of the most prevalent chronic progressive bone diseases, is caused by deficiency in bone formation by osteoblasts or excessive bone resorption by osteoclasts and subsequently increases the risk of bone fractures. Emerging evidence has indicated that long noncoding RNAs (lncRNAs) play key roles in many biological processes and various disorders. However, the role and mechanism of HOX antisense intergenic RNA myeloid 1 (HOTAIRM1), a myeloid-specific lncRNA, in osteoclast differentiation, osteogenic differentiation, and OP remain unclear. In this study, we found that HOTAIRM1 was upregulated during ossification of ligamentum flavum and osteogenic differentiation, while it was downregulated in osteoclast differentiation and in the bone and serum of human and mouse with OP. Further investigation revealed that silencing Hotairm1 decreased the expression of the osteogenic markers and attenuated osteogenesis. Moreover, forced Hotairm1 expression inhibited the expressions of the osteoclastogenesis markers and alleviated receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL)-induced osteoclast differentiation. Mechanically, Hotairm1 repressed the phosphorylation of p65 and inhibitor of κBα (IκBα) and attenuated RANKL-mediated enhancement of phos-p65 and IκBα, suggesting that Hotairm1 inhibits RANKL-induced osteoclastogenesis through the NF-κB pathway. In conclusion, our data identified a crucial role of HOTAIRM1 in OP, providing a proof of this molecule as a potential diagnostic marker and a possible therapeutic target against OP.

Diagnostic and prognostic roles of soluble CD22 in patients with Gram-negative bacterial sepsis.

BACKGROUND: Soluble CD22 (sCD22) is a fragment of CD22, a B cell-specific membrane protein that negatively regulates B-cell receptor signaling. To date, sCD22 has only been regarded as a tumor marker of B-cell malignancies. Its expression in infectious diseases has not yet been assessed. METHODS: Serum concentrations of sCD22, procalcitonin (PCT) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assays in patients with intra-abdominal Gram-negative bacterial infection. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of these biomarkers in this type of infection. The correlations between biomarkers and the Acute Physiology and Chronic Health Evaluation (APACHE) II scores were also analyzed. RESULTS: Concentrations of sCD22 were significantly elevated in patients with sepsis and the elevation is correlated with the severity of sepsis. sCD22 was also slightly elevated in patients with non-infected systemic inflammatory response syndrome or local infection. The diagnostic accuracy of sCD22 for sepsis was equivalent to that of PCT or IL-6. In addition, the correlation of sCD22 with APACHE II scores was stronger than that of PCT or IL-6. CONCLUSIONS: Serum sCD22 is a novel inflammatory mediator released during infection. This soluble biomarker plays a potential role in the diagnosis of Gram-negative bacterial sepsis, with a diagnostic accuracy as efficient as that of PCT or IL-6. Furthermore, sCD22 is more valuable to predict the outcomes in patients with sepsis than PCT or IL-6. The present study suggested that sCD22 might be potentially useful in supplementing current criteria for sepsis.

Effect of HbA1C detection on the diagnostic screening for glucose metabolic disorders in polycystic ovary syndrome.

PURPOSE: This study aimed to assess the effect of hemoglobin A1C (HbA1C) detection on the diagnostic screening for glucose metabolic disorders in women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: A total of 161 patients with PCOS (mean age = 23.68 +/- 4.23 years) were subjected to an oral glucose tolerance test (OGTT). The receiver operating characteristic (ROC) curve was plotted to evaluate the fasting plasma glucose (FPG), and HbA1C was used to probe the sensitivity and specificity of abnormal glucose tolerance. RESULTS: Based on the traditional standards of blood sugar, the prevalence of type 2 diabetes was 5.6%, and the pre-diabetes prevalence was 7.5%. Based on the HbA1C standards, 4.3% of patients were diagnosed with type 2 diabetes, and 10.6% of the diabetic patients can be considered as high-risk populations. Based on the combined standards of OGTT and HbA1C, the prevalence of type 2 diabetes was 6.2%, and the pre-diabetes prevalence was 12.4%. OGTT is considered the gold standard for identifying abnormal glucose tolerance, and HbA1C detection is considered to be stronger than FPG. The areas under the ROC curves of HbA1C and FPG were 0.968 and 0.672, respectively (p < 0.01). The American Diabetes Association (ADA) recommends the cut-off value of HbA1c > or = 5.7% and FPG > or = 5.6 mmol/l for identifying abnormal glucose tolerance. The sensitivity and specificity were 76.7% and 89.5% for HBA1C, as well as 40.5% and 94.3% for FPG, respectively. The positive and negative likelihood ratios were 7.3 and 0.26 for HbA1C, as well as 7.1 and 0.63 for FPG, respectively. CONCLUSION: HbA1C detection can be used as a method for diagnosis and screening.

Nepetoidin B Alleviates Liver Ischemia/Reperfusion Injury via Regulating MKP5 and JNK/P38 Pathway.

Background: Nepetoidin B (NB) has been reported to possess anti-inflammatory, antibacterial, and antioxidant properties. However, its effects on liver ischemia/reperfusion (I/R) injury remain unclear. Methods: In this study, a mouse liver I/R injury model and a mouse AML12 cell hypoxia reoxygenation (H/R) injury model were used to investigate the potential role of NB. Serum transaminase levels, liver necrotic area, cell viability, oxidative stress, inflammatory response, and apoptosis were evaluated to assess the effects of NB on liver I/R and cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to measure mRNA and protein expression levels, respectively. Molecular docking was used to predict the binding capacity of NB and mitogen-activated protein kinase phosphatase 5 (MKP5). Results: The results showed that NB significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver necrosis, oxidative stress, reactive oxygen species (ROS) content, inflammatory cytokine content and expression, inflammatory cell infiltration, and apoptosis after liver I/R and AML12 cells H/R injury. Additionally, NB inhibited the JUN protein amino-terminal kinase (JNK)/P38 pathway. Molecular docking results showed good binding between NB and MKP5 proteins, and Western blotting results showed that NB increased the protein expression of MKP5. MKP5 knockout (KO) significantly diminished the protective effects of NB against liver injury and its inhibitory effects on the JNK/P38 pathway. Conclusion: NB exerts hepatoprotective effects against liver I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.

The PD-1 /PD-L1 signaling pathway regulates decidual macrophage polarization and may participate in preeclampsia.

The pathogenesis of preeclampsia (PE) has not been elucidated, but immune imbalance is known to be one of the main pathogeneses. Dysfunction of decidual macrophages can lead to PE, and the PD-1/PD-L1 signaling pathway is associated with macrophage polarization. However, the relationship between the influence of the PD-1/PD-L1 signaling pathway on macrophage polarization and the onset of PE has not been fully elucidated. In this study, we analyzed the expression of CD68, iNOS, CD206, PD-1 and PD-L1 and the coexpression of CD68+PD-1+ and CD68+PD-L1+ in the decidual tissue of PE patients (n= 18) and healthy pregnant women (n=20). We found that CD68 and iNOS expression was increased in the decidua of PE patients (P < 0.001) and that CD206, PD-1 and PD-L1 expression and CD68+PD-1+ and CD68+PD-L1+ coexpression were decreased (P < 0.001). To assess the influence of the PD-1/PD-L1 signaling pathway on macrophage polarization, we added an anti-PD-1 mAb (pembrolizumab) or an anti-PD-L1 mAb (durvalumab) during THP-1 differentiation into M1 macrophages. Then, we detected the polarization of CD68+CD80+ macrophages and the expression of iNOS. To examine the effect of macrophage polarization on the invasion ability of trophoblast cells, macrophages were cocultured with HTR8/SVneo cells, and the invasion ability of HTR8/SVneo cells was detected via transwell assays. We found that CD68+CD80+ macrophage polarization was enhanced (P<0.05) and that iNOS expression was greater (P<0.01) in the pembrolizumab group. In the durvalumab group, CD68+CD80+ macrophage polarization and iNOS expression were also increased (P<0.05 and P<0.001). Compared with that in the untreated group, the aggressiveness of HTR8/SVneo cells was decreased in both the pembrolizumab group (P < 0.01) and the durvalumab group (P < 0.001). These findings indicate that the PD-1/PD-L1 signaling pathway may play an important role in the pathogenesis of PE by influencing macrophage polarization and reducing the invasion ability of trophoblasts.

6-Gingerol attenuates hepatic ischemia/reperfusion injury through regulating MKP5-mediated P38/JNK pathway.

6-Gingerol, the main bioactive compound of ginger, has antioxidant, anti-inflammatory, anti-cancer and neuroprotective effects. However, it is unclear whether 6-Gingerol has protective effects against hepatic ischemia/reperfusion (I/R) injury. In this study, the mouse liver I/R injury model and the mouse AML12 cell hypoxia/reoxygenation (H/R) model were established by pretreatment with 6-Gingerol at different concentrations to explore the potential effects of 6-Gingerol. Serum transaminase levels, liver necrotic area, cell viability, inflammatory response, and cell apoptosis were used to assess the effect of 6-Gingerol on hepatic I/R or cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to detect the mRNA and protein expression. The results show that 6-Gingerol decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, liver necrosis, inflammatory cytokines IL-1ß, IL-6, MCP-1, TNF-α expression, Ly6g+ inflammatory cell infiltration, protein phosphorylation of NF-κB signaling pathway, Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) positive cells, cell apoptosis rate, the protein expression of pro-apoptotic protein BAX and C-Caspase3, increased cell viability, and expression of anti-apoptotic protein BCL-2. Moreover, 6-Gingerol could increase the mRNA and protein expression of mitogen activated protein kinase phosphatase 5 (MKP5) and inhibit the activation of P38/JNK signaling pathway. In MKP5 knockout (KO) mice, the protective effect of 6-gingerol and the inhibition of P38/JNK pathway were significantly weakened. Therefore, our results suggest that 6-Gingerol exerts anti-inflammatory and anti-apoptotic effects to attenuate hepatic I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.

The value of PET/CT in the diagnosis and differential diagnosis of Parkinson's disease: a dual-tracer study.

Positron emission tomography/computed tomography (PET/CT) is a molecular imaging method commonly used to diagnose and differentiate Parkinson's disease (PD). This study aimed to evaluate the performance of PET/CT with 11C-2ß-Carbomethoxy-3ß-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) tracers in the differential diagnosis between PD, multiple system atrophy parkinsonian type (MSA-P), progressive supranuclear palsy (PSP) and vascular parkinsonism (VP) using the data of 220 patients with clinical PD-like symptoms. Of the 220 enrolled patients, 166 (PD, n = 80; MSA-P, n = 54; PSP, n = 15; VP, n = 17) completed the motor, cognitive and PET/CT assessment and were included in this study. 11C-CFT and 18F-FDG PET/CT images were analyzed using the SNBPI toolbox and CortexID Suite software. The uptake values of 11C-CFT and 18F-FDG PET/CT were compared among the groups after controlling for covariates using generalized linear models. Receiver operating characteristic (ROC) curves were generated to estimate the diagnostic values. Patients with PSP showed the most significant reduction on 11C-CFT PET/CT, while patients with PD and MSA-P showed similar reductions, and patients with VP did not show any significant reduction in 11C-CFT uptake. The areas under the curve (AUCs) for 11C-CFT PET/CT for distinguishing PD from VP, PSP, and MSA-P were 0.902, 0.830, and 0.580, respectively, and 0.728 for distinguishing advanced-stage PD from PSP. On 18F-FDG PET/CT, the AUCs for distinguishing PD from PSP and MSA-P were 0.968 and 0.963, respectively. These results suggest that 11C-CFT and 18F-FDG PET/CT complement each other in improving the accuracy in differential diagnosis of PD.

Editable 3D Micro-Supercapacitor with High Energy Density Based on Mortise-Tenon Joint Structures.

Three-dimensional micro-supercapacitors (3D MSCs) have accelerated the development of microenergy-storage modules for miniaturized and portable electronics. However, the low energy density, complex construction strategy, and low assembly accuracy of a 3D MSC restrict its practical application. Herein, we design a simple construction strategy for a 3D MSC with high energy density by mortise and tenon structures. Wood-derived carbon modified by nitrogen-doped carbon nanotube arrays (N-CNT-WDC) provides an ordered ion transport channel and a large active specific surface area, availing the improvement of the energy density of a 3D MSC. Its strong carbon skeleton structure supports the construction of 3D interdigital electrodes with a tenon structure by laser, realizing precise and regulable assembly of 3D MSCs through a mortise and tenon joint. The prepared 3D MSC based on N-CNT-WDC shows an excellent volumetric capacitance of 93.66 F cm-3, a high volumetric energy density of 12 mW h cm-3 at 600 mA cm-3, and an 85% retention rate of capacitance after 10,000 cycles of charge and discharge at 1000 mA cm-3. Furthermore, the mortise and tenon structure realizes diversified integration of 3D MSCs, making the integrated manufacturing of 3D microdevices more convenient and promoting their application in microelectronic devices.

Excessive Immune Activation and the Correlation with Decreased Expression of PD-1 at the Maternal-Fetal Interface in Preeclampsia.

The etiology of preeclampsia (PE) is still unknown, and excessive immune activation is an important component of its pathogenesis. Programmed cell death protein 1 (PD-1) is one of immune checkpoints which may prevent overactivated immune attack and lead to a tolerant immune microenvironment. Little is known about the involvement of PD-1-mediated immunoregulation at the maternal-fetal interface in PE. To investigate the inflammatory pattern and the involvement of PD-1 in the decidua of women with PE, decidual tissues were obtained from PE and control pregnant women. Quantitative RT-PCR analysis of the mRNA levels of the inflammatory cytokines was performed. PD-1 expression was detected by immunohistochemistry, western blot analysis, and flow cytometry. To prove the role of PD-1, decidual immune cells were incubated with blocking antibodies, and the inflammatory cytokines were detected by ELISA. We observed that the mRNA levels of IL-1ß, IL-6, TNF-α, and IFN-γ were higher in the decidua of the PE group than in the decidua of the control group. The mRNA levels of IL-4 and IL-10 were lower in PE. The expression level of PD-1 was significantly downregulated, and the proportion (%) of PD-1 + CD45 + cells was significantly lower in PE. There was a significant linear correlation between PD-1 expression and common proinflammatory cytokines in the decidua. Anti-PD-1 blocking antibody significantly increased the secretion of proinflammatory cytokines. Our data suggested that the inflammatory pattern and decreased PD-1 expression in the decidua might play an active role in the local immunoregulatory mechanisms of PE. The PD-1 pathway in the maternal-fetal interface possibly function to break the tolerant immune microenvironment in PE via inflammatory cytokines.

[Effects of moxibustion on serum levels of ß-EP, SP and expression of IL-1ß and COX-2 protein in brainstem in rats with migraine].

OBJECTIVE: To observe the effects of moxibustion at "Baihui" (GV 20) and "Dazhui" (GV 14) at different time points on the serum level of ß-endorphin (ß-EP), substance P (SP) and expression of interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2) protein in brainstem in rats with migraine, and to explore the effect and mechanism of moxibustion in preventing and treating migraine. METHODS: Forty male SD rats were randomly divided into a blank group, a model group, a prevention+treatment (PT) group and a treatment group, 10 rats in each group. Except the blank group, the rats in the remaining groups were injected with nitroglycerin subcutaneously to prepare migraine model. The rats in the PT group were treated with moxibustion 7 days before modeling (once a day) and 30 min after modeling, while the rats in the treatment group were treated with moxibustion 30 min after modeling. The "Baihui" (GV 20) and "Dazhui" (GV 14) were taken for 30 minutes each time. The behavioral scores in each group were observed before and after modeling. After intervention, ELISA method was used to detect the serum level of ß-EP and SP; the immunohistochemistry method was used to detect the number of positive cells of IL-1ß in brainstem; the Western blot method was used to detect the expression of COX-2 protein in brainstem. RESULTS: Compared with the blank group, the behavioral scores in the model group were increased 0-30 min, 60-90 min and 90-120 min after modeling (P<0.01); compared with the model group, in the treatment group and the PT group, the behavioral scores were decreased 60-90 min and 90-120 min after modeling (P<0.01). Compared with the blank group, in the model group, the serum level of ß-EP was decreased (P<0.01), while the serum level of SP, the number of positive cells of IL-1ß in brainstem and the expression of COX-2 protein were increased (P<0.01). Compared with the model group, in the PT group and and the treatment group, the serum level of ß-EP was increased (P<0.01), while the serum level of SP, the number of positive cells of IL-1ß and the expression of COX-2 protein in brainstem were decreased (P<0.01, P<0.05). Compared with the treatment group, in the PT group, the serum level of ß-EP was increased and COX-2 protein expression was decreased (P<0.05). CONCLUSION: Moxibustion could effectively relieve migraine. The mechanism may be related to reduce the serum level of SP, IL-1ß and COX-2 protein expression in brainstem, and increase the serum level of ß-EP, and the optimal effect is observed in the PT group.

STARD5 as a potential clinical target of hepatocellular carcinoma.

To reveal whether STARD5 is a potential biomarker for diagnosis and prognosis of HCC. Using gene expression omnibus and the cancer genome atlas (TCGA) to screen differentially expressed genes in HCC and STARD5 was selected by LASSO algorithm. Then, we analyzed the association between STARD5 and clinical characteristics of HCC patients in TCGA and International Cancer Genome Consortium. Meanwhile, the mRNA and protein level of STARD5 was also verified by collecting 87 cases of HCC patients' liver tissues using qRT-PCR and WB. Next, we applied gene set enrichment analysis (GSEA) for pathways analysis of STARD5. Finally, TIMER1.0 and TISIDB were used to explore the correlation of STARD5 with immune cell infiltration. The expression of STARD5 was lower in HCC and negatively correlated with tumor grade (p < 0.05), while high expression of STARD5 suggested a better prognosis for HCC patients (p < 0.01) and it could be an independent prognostic predictor (p < 0.001). Meanwhile, STARD5 also had strong diagnostic accuracy for HCC patients. GSEA revealed that STARD5-related genes were mainly enriched in E2F targets, G2M checkpoint and KRAS signaling. The TIMER1.0 and TISIDB databases found a negative correlation between STARD5 and tumor immune infiltrating cells. STARD5 could be used as a potential target for HCC diagnosis and prognosis.

An injectable superior depot of Telratolimod inhibits post-surgical tumor recurrence and distant metastases.

The clinical success of Toll-like receptor (TLR) agonists is based on their capacity to efficiently mobilize both innate and adaptive immunity. However, rapid distribution of TLR agonists into the systemic circulation may result in systemic cytokine storms. Telratolimod (Tel) is a TLR 7/8 agonist whose structure has a hydrophobic long chain that helps to prolong its release. Despite this, the phase I study of Tel showed cytokine release syndromes in 3/35 patients. Herein, we designed an injectable phase transition gel (PGE) that served as a superior drug depot for fatty acid-modified drugs. PGE further minimized the systemic drug exposure of Tel and the possible cytokine storms. In vivo studies demonstrated that Tel@PGE facilitated the recruitment of effector CD8+ T lymphocytes (T cells) and the polarization of myeloid-derived suppressor cells (MDSCs) and immunosuppressive M2-like macrophages to tumoricidal antigen-presenting cells. The reshaping of the tumor microenvironment (TME) by Tel@PGE elicited systematic immune responses to significantly prevent B16F10 or 4T-1 tumor postoperative recurrence and metastasis. Therefore, this platform of Tel is expected to provide a clinically available option for effective postoperative combined therapy. STATEMENT OF SIGNIFICANCE: A series of prodrugs or conjugates containing hydrophobic blocks were designed to achieve sustained release at the injection site by reducing the water solubility. However, this strategy sometimes failed short of expectations. Thus, we constructed a biocompatible and biodegradable injectable phase transition gel (PGE) with superior release properties that can be injected subcutaneously into the surgery site. In the long-lasting treatment, the melanoma and breast cancer immunotherapeutic effect significantly enhanced and the risk of cancer metastasis and relapse was reduced. Crucially, for some immune agonists, a superior release control can significantly reduce adverse effects which was decisive for the availability of the drugs.