ICG-labeled PD-L1-antagonistic affibody dimer for tumor imaging and enhancement of tumor photothermal-immunotherapy.

In clinical practice, tumor-targeting diagnosis and immunotherapy against programmed death ligand 1 (PD-L1) have a significant impact. In this research, a PD-L1-antagonistic affibody dimer (ZPD-L1) was successfully prepared through Escherichia coli expression system, and conjugated with the photosensitizer of ICG via N-hydroxysuccinimide (NHS) ester to develop a novel tumor-targeting agent (ICG-ZPD-L1) for both tumor imaging diagnosis and photothermal-immunotherapy simultaneously. In vitro, ZPD-L1 could specifically bind to PD-L1-positive LLC and MC38 tumor cells, and ICG-ZPD-L1-mediated photothermal therapy (PTT) also showed excellent phototoxicity to these tumor cells. In vivo, ICG-ZPD-L1 selectively enriched into the PD-L1-positive MC38 tumor tissues, and the high-contrast optical imaging of tumors was obtained. ICG-ZPD-L1-mediated PTT exhibited a potent anti-tumor effect in vivo due to its remarkable photothermal properties. Furthermore, ICG-ZPD-L1-mediated PTT significantly induced the immunogenic cell death (ICD) of primary tumors, promoted maturation of dendritic cells (DCs), up-regulated anti-tumor immune response, enhanced immunotherapy, and superiorly inhibited the growth of metastatic tumors. In addition, ICG-ZPD-L1 showed favorable biosafety throughout the brief duration of treatment. In summary, these results suggest that ICG-ZPD-L1 is a multifunctional tumor-targeting drug integrating tumor imaging diagnosis and photothermal-immunotherapy, and has great guiding significance for the diagnosis and treatment of clinical PD-L1-positive tumor patients.

Learning a Contact Potential Field for Modeling the Hand-Object Interaction.

Estimating and synthesizing the hand's manipulation of objects is central to understanding human behaviour. To accurately model the interaction between the hand and object (referred to as the "hand-object"), we must not only focus on the pose of the hand and object, but also consider the contact between them. This contact provides valuable information for generating semantically and physically plausible grasps. In this paper, we propose an explicit contact representation called Contact Potential Field (CPF). In CPF, we model the contact between a pair of hand-object vertices as a spring-mass system. This system encodes the distance of the pair, as well as a likelihood of that contact being stable. Therefore, the system of multiple extended and compressed springs forms an elastic potential field with minimal energy at the optimal grasp position. We apply CPF to two relevant tasks, namely, hand-object pose estimation and grasping pose generation. Extensive experiments on the two challenging tasks and three commonly used datasets have demonstrated that our method can achieve state-of-the-art in several reconstruction metrics, allowing us to produce more physically plausible hand-object poses even when the ground-truth exhibits severe interpenetration or disjointedness. Our model and source codes are made publicly available at https://github.com/lixiny/CPF.

ER stress promotes mitochondrial calcium overload and activates the ROS/NLRP3 axis to mediate fatty liver ischemic injury.

BACKGROUND: Fatty livers are widely accepted as marginal donors for liver transplantation but are more susceptible to liver ischemia and reperfusion (IR) injury. Increased macrophage-related inflammation plays an important role in the aggravation of fatty liver IR injury. Here, we investigate the precise mechanism by which endoplasmic reticulum (ER) stress activates macrophage NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) signaling by regulating mitochondrial calcium overload in fatty liver IR. METHODS: Control- and high-fat diet-fed mice were subjected to a partial liver IR model. The ER stress, mitochondrial calcium levels, and NLRP3 signaling pathway in macrophages were analyzed. RESULTS: Liver steatosis exacerbated liver inflammation and IR injury and enhanced NLRP3 activation in macrophages. Myeloid NLRP3 deficiency attenuated intrahepatic inflammation and fatty liver injury following IR. Mechanistically, increased ER stress and mitochondrial calcium overload were observed in macrophages obtained from mouse fatty livers after IR. Suppression of ER stress by tauroursodeoxycholic acid effectively downregulated mitochondrial calcium accumulation and suppressed NLRP3 activation in macrophages, leading to decreased inflammatory IR injury in fatty livers. Moreover, Xestospongin-C-mediated inhibition of mitochondrial calcium influx decreased reactive oxygen species (ROS) expression in macrophages after IR. Scavenging of mitochondrial ROS by mito-TEMPO suppressed macrophage NLRP3 activation and IR injury in fatty livers, indicating that excessive mitochondrial ROS production was responsible for macrophage NLRP3 activation induced by mitochondrial calcium overload. Patients with fatty liver also exhibited upregulated activation of NLRP3 and the ER stress signaling pathway after IR. CONCLUSIONS: Our findings suggest that ER stress promotes mitochondrial calcium overload to activate ROS/NLRP3 signaling pathways within macrophages during IR-stimulated inflammatory responses associated with fatty livers.

Multiple sclerosing hemangiomas mimicking hepatocellular carcinoma: A case report.

Hepatocellular carcinoma is a prevalent malignant tumor affecting the liver, and surgical resection and liver transplantation are the primary treatment options for early-stage HCC patients. However, the presence of benign hepatic tumors with similar imaging characteristics to HCC poses challenges in diagnosing and treating the disease, often resulting in misdiagnosis and inappropriate treatment. This case report presents a 52-year-old female patient who exhibited space-occupying liver lesions on abdominal CT and MRI scans. Based on pathological sections from other hospitals, liver malignancy was highly suspected, and hepatocellular tumor was diagnosed preoperatively. But the tumor markers of the patient were all within the normal range. After evaluating the overall condition of the patient, we finally chose the diagnosis and treatment of dissection and partial hepatectomy. Surprisingly, the final diagnosis of postoperative pathology was sclerosing hemangioma. The patient recovered well and was discharged 2 weeks later. Hepatic sclerosing hemangioma is an extremely rare disease that can be easily mistaken for malignant liver tumors due to absence of typical imaging presentations. The diagnosis also needs to be differentiated from other benign tumors, such as liver adenoma and liver abscess, according to the medical history, symptoms, and auxiliary examinations. Therefore, special attention should be given to the diagnosis and treatment of sclerosing hemangioma.

Defective efferocytosis by aged macrophages promotes STING signaling mediated inflammatory liver injury.

Aged livers have shown aggravated liver ischemia and reperfusion (IR) injury. Timely efferocytosis of apoptotic cells is a key mechanism for avoiding excessive inflammation and tissue injury. Here, we investigated the alteration of efferocytosis by aged macrophages and its role in regulating macrophage STING (stimulator of interferon genes) signaling and liver IR injury. Aged and young mice were subjected to liver partial IR model. Liver injury and inflammation were measured. Efferocytosis by aged macrophages and the underlying regulatory mechanism were analyzed as well. Aged macrophages exhibited impaired efferocytosis with decreased MerTK (c-mer proto-oncogene tyrosine kinase) activation, which was reversed by treatment of the MerTK CRISPR activation plasmid. Increased MerTK cleavage by ADAM17 (a disintegrin and metalloproteinase 17) due to enhanced ROS (reactive oxygen species) levels contributed to defective efferocytosis by aged macrophages. MerTK activation by suppressing ADAM17 or ROS improved aged macrophage efferocytosis, leading to reduced inflammatory liver injury. Moreover, increased apoptotic hepatocytes, DNA accumulation, and macrophage STING activation were observed in aged ischemic livers. Improvement in efferocytosis by aged macrophages via MerTK activation suppressed STING activation and inflammatory liver injury. Our study demonstrates that aging suppresses MerTK- mediated macrophage efferocytosis to promote macrophage STING activation and inflammatory liver IR injury, suggesting a new mechanism and potential therapy to promote inflammation resolution and efferocytosis in aged livers.

Revolutionary approaches for cancer diagnosis by terahertz-based spectroscopy and imaging.

Most tumors are easily missed and misdiagnosed due to the lack of specific clinical signs and symptoms in the early stage. Thus, an accurate, rapid and reliable early tumor detection method is highly desirable. The application of terahertz (THz) spectroscopy and imaging in biomedicine has made remarkable progress in the past two decades, which addresses the shortcomings of existing technologies and provides an alternative for early tumor diagnosis. Although issues such as size mismatch and strong absorption of THz waves by water have set hurdles for cancer diagnosis by THz technology, innovative materials and biosensors in recent years have led to possibilities for new THz biosensing and imaging methods. In this article, we reviewed the issues that need to be solved before THz technology is used for tumor-related biological sample detection and clinical auxiliary diagnosis. We focused on the recent research progress of THz technology, with an emphasis on biosensing and imaging. Finally, the application of THz spectroscopy and imaging for tumor diagnosis in clinical practice and the main challenges in this process were also mentioned. Collectively, THz-based spectroscopy and imaging reviewed here is envisioned as a cutting-edge approach for cancer diagnosis.

Macrophage STING signaling promotes NK cell to suppress colorectal cancer liver metastasis via 4-1BBL/4-1BB co-stimulation.

BACKGROUND AND AIMS: Macrophage innate immune response plays an important role in tumorigenesis. However, the role and mechanism of macrophage STING signaling in modulating tumor microenvironment to suppress tumor growth at secondary sites remains largely unclear. METHODS: STING expression was assessed in liver samples from patients with colorectal cancer (CRC) liver metastasis. Global or myeloid stimulator of interferon gene (STING)-deficient mice, myeloid NOD-like receptor protein 3 (NLRP3)-deficient mice, and wild-type (WT) mice were subjected to a mouse model of CRC liver metastasis by intrasplenic injection of murine colon carcinoma cells (MC38). Liver non-parenchymal cells including macrophages and natural killer (NK) cells were isolated for flow cytometry analysis. Bone marrow-derived macrophages pretreated with MC38 were co-cultured with splenic NK cells for in vitro studies. RESULTS: Significant activation of STING signaling were detected in adjacent and tumor tissues and intrahepatic macrophages. Global or myeloid STING-deficient mice had exacerbated CRC liver metastasis and shorten survival, with decreased intrahepatic infiltration and impaired antitumor function of NK cells. Depletion of NK cells in WT animals increased their metastatic burden, while no significant effects were observed in myeloid STING-deficient mice. STING activation contributed to the secretion of interleukin (IL)-18 and IL-1ß by macrophages, which optimized antitumor activity of NK cells by promoting the expression of 4-1BBL in macrophages and 4-1BB in NK cells, respectively. Moreover, MC38 treatment activated macrophage NLRP3 signaling, which was inhibited by STING depletion. Myeloid NLRP3 deficiency increased tumor burden and suppressed activation of NK cells. NLRP3 activation by its agonist effectively suppressed CRC liver metastasis in myeloid SITNG-deficient mice. CONCLUSIONS: We demonstrated that STING signaling promoted NLRP3-mediated IL-18 and IL-1ß production of macrophages to optimize the antitumor function of NK cells via the co-stimulation signaling of 4-1BBL/4-1BB.

MLKL deficiency attenuated hepatocyte oxidative DNA damage by activating mitophagy to suppress macrophage cGAS-STING signaling during liver ischemia and reperfusion injury.

Mixed-lineage kinase domain-like protein (MLKL)-mediated necroptosis has been implicated in aggravating liver ischemia and reperfusion (IR) injury. However, the precise role and mechanism of MLKL in regulating oxidative DNA damage of hepatocytes and subsequent activation of macrophage stimulator of interferon genes (STING) signaling remains unclear. In this study, we investigated the role of MLKL in regulating the interplay between hepatocyte injury and macrophage pro-inflammatory responses during liver IR injury. We found that IR increased MLKL expression in liver tissues of wild type (WT) mice. MLKL knockout (KO) attenuated liver IR injury and suppressed the activation of cGAS-STING signaling in intrahepatic macrophages, which was abrogated by STING activation with its agonist. Mechanistically, IR induced oxidative DNA damage in hepatocytes, leading to cGAS-STING activation in macrophages, which was suppressed by MLKL KO. Moreover, increased PTEN-induced kinase 1 (PINK1)-mediated mitophagy contributed to reduced oxidative DNA damage in hepatocytes and subsequent decreased activation of STING signaling in macrophages in MLKL KO mice. Our findings demonstrated a non-canonical role of MLKL in the pathogenesis of liver IR. MLKL deficiency significantly promoted PINK1-mediated mitophagy activation to inhibit oxidative DNA damage in hepatocytes, which in turn suppressed macrophage cGAS-STING activation and inflammatory liver IR injury.

Atomically Dispersed Mn for Electrochemical CO2 Reduction with Tunable Performance.

Electrochemical CO2 reduction (ECR) is recognized as a sustainable and promising approach for the production of high-value chemicals. To facilitate widespread application of this technology, the design and construction of efficient cathodic electrocatalysts is critically important. Here we report the synthesis of atomically dispersed manganese on nitrogen-doped porous carbon (Mn SAs/NC) using a facile and scalable annealing method for catalyzing the ECR reaction. The as-obtained Mn SAs/NC delivers high activity and selectivity toward CO formation with a faradaic efficiency of 80.5±0.6%, over 5 times that of bare NC. The high activity is preserved even after 10 h of continuous polarization. The catalytic properties of our cost-effective Mn SAs/NC catalyst are readily tuned by regulating the nitrogen configurations and the percentage of Mn SAs via modulation of the nitrogen precursor and the thermal treatment conditions.

Combined Therapy of Yishen Zhuanggu Decoction and Caltrate D600 Alleviates Postmenopausal Osteoporosis by Targeting FoxO3a and Activating the Wnt/ß-Catenin Pathway.

Background: Postmenopausal osteoporosis (PMO) is the most prevalent metabolic bone disease in women. Yishen Zhuanggu (YSZG) decoction and Caltrate D600 reportedly affects bone formation. This study aimed to investigate the efficacy and mechanism of YSZG decoction combined with Caltrate D600 in PMO treatment. Methods: Ovariectomy-induced PMO rat model was treated with YSZG or/and Caltrate D600 for 12 weeks. Femur bone mineral density (BMD), osteoporosis-related protein expression, and serum parameters were measured. Pathological features of femur bone tissues were observed using hematoxylin and eosin staining. Serum levels of oxidative stress parameters were measured using corresponding commercial kits. The mRNA and protein expression of FoxO3a, Wnt, and ß-catenin was detected using qRT-PCR and western blotting. Results: The BMD and ultimate load of PMO rats were increased after treatment with YSZG. YSZG treatment promoted the bone trabeculae formation of PMO rats. YSZG treatment also induced bone differentiation and suppress oxidative stress in PMO rats, evidenced by the increased BALP, Runx2, OPG, SOD, and CAT levels, as well as the decreased TRACP 5b, RANKL, ROS, and MDA levels. Additionally, YSZG treatment downregulated the FoxO3a expression and upregulated the levels of Wnt and ß-catenin in PMO rats. Caltrate D600 addition showed an auxiliary effect for YSZG. Conclusion: YSZG decoction exerts the antiosteoporotic effect on PMO by restraining the FoxO3a expression and activating the Wnt/ß-catenin pathway, which has an impressive synergistic effect with Caltrate D600.

THz-ATR Spectroscopy Integrated with Species Recognition Based on Multi-Classifier Voting for Automated Clinical Microbial Identification.

The demand for rapid and accurate identification of microorganisms is growing due to considerable importance in all areas related to public health and safety. Here, we demonstrate a rapid and label-free strategy for the identification of microorganisms by integrating terahertz-attenuated total reflection (THz-ATR) spectroscopy with an automated recognition method based on multi-classifier voting. Our results show that 13 standard microbial strains can be classified into three different groups of microorganisms (Gram-positive bacteria, Gram-negative bacteria, and fungi) by THz-ATR spectroscopy. To detect clinical microbial strains with better differentiation that accounts for their greater sample heterogeneity, an automated recognition algorithm is proposed based on multi-classifier voting. It uses three types of machine learning classifiers to identify five different groups of clinical microbial strains. The results demonstrate that common microorganisms, once time-consuming to distinguish by traditional microbial identification methods, can be rapidly and accurately recognized using THz-ATR spectra in minutes. The proposed automatic recognition method is optimized by a spectroscopic feature selection algorithm designed to identify the optimal diagnostic indicator, and the combination of different machine learning classifiers with a voting scheme. The total diagnostic accuracy reaches 80.77% (as high as 99.6% for Enterococcus faecalis) for 1123 isolates from clinical samples of sputum, blood, urine, and feces. This strategy demonstrates that THz spectroscopy integrated with an automatic recognition method based on multi-classifier voting significantly improves the accuracy of spectral analysis, thereby presenting a new method for true label-free identification of clinical microorganisms with high efficiency.

JAML promotes acute kidney injury mainly through a macrophage-dependent mechanism.

Although macrophages are undoubtedly attractive therapeutic targets for acute kidney injury (AKI) because of their critical roles in renal inflammation and repair, the underlying mechanisms of macrophage phenotype switching and efferocytosis in the regulation of inflammatory responses during AKI are still largely unclear. The present study elucidated the role of junctional adhesion molecule-like protein (JAML) in the pathogenesis of AKI. We found that JAML was significantly upregulated in kidneys from 2 different murine AKI models including renal ischemia/reperfusion injury (IRI) and cisplatin-induced AKI. By generation of bone marrow chimeric mice, macrophage-specific and tubular cell-specific Jaml conditional knockout mice, we demonstrated JAML promoted AKI mainly via a macrophage-dependent mechanism and found that JAML-mediated macrophage phenotype polarization and efferocytosis is one of the critical signal transduction pathways linking inflammatory responses to AKI. Mechanistically, the effects of JAML on the regulation of macrophages were, at least in part, associated with a macrophage-inducible C-type lectin-dependent mechanism. Collectively, our studies explore for the first time to our knowledge new biological functions of JAML in macrophages and conclude that JAML is an important mediator and biomarker of AKI. Pharmacological targeting of JAML-mediated signaling pathways at multiple levels may provide a novel therapeutic strategy for patients with AKI.

Engineering the CuO-HfO2 interface toward enhanced CO2 electroreduction to C2H4.

We report significantly enhanced electrochemical CO2 reduction (ECR) to C2H4 by tuning the interface of a metal oxide composite (CuOx/HfO2), enabling a C2H4 faradaic efficiency as high as 62.6 ± 1.3% at 300 mA cm-2, in contrast to only 11.6 ± 1.6% over pure CuO. Collective knowledge from multiple control experiments, density functional theory calculations, and operando Raman study reveals that the CuOx-HfO2 interface greatly strengthens CO2 adsorption and the binding of *CO for further C-C coupling to yield C2H4.

A multiplexed circulating tumor DNA detection platform engineered from 3D-coded interlocked DNA rings.

Circulating tumor DNA (ctDNA) is a critical biomarker not only important for the early detection of tumors but also invaluable for personalized treatments. Currently ctDNA detection relies on sequencing. Here, a platform termed three-dimensional-coded interlocked DNA rings (3D-coded ID rings) was created for multiplexed ctDNA identification. The ID rings provide a ctDNA recognition ring that is physically interlocked with a reporter ring. The specific binding of ctDNA to the recognition ring initiates target-responsive cutting via a restriction endonuclease; the cutting then triggers rolling circle amplification on the reporter ring. The signals are further integrated with internal 3D codes for multiplexed readouts. ctDNAs from non-invasive clinical specimens including plasma, feces, and urine were detected and validated at a sensitivity much higher than those obtained through sequencing. This 3D-coded ID ring platform can detect any multiple DNA fragments simultaneously without sequencing. We envision that our platform will facilitate the implementation of future personalized/precision medicine.

A Novel and Rapid Serum Detection Technology for Non-Invasive Screening of Gastric Cancer Based on Raman Spectroscopy Combined With Different Machine Learning Methods.

Gastric cancer (GC) is the fifth most common cancer in the world and a serious threat to human health. Due to its high morbidity and mortality, a simple, rapid and accurate early screening method for GC is urgently needed. In this study, the potential of Raman spectroscopy combined with different machine learning methods was explored to distinguish serum samples from GC patients and healthy controls. Serum Raman spectra were collected from 109 patients with GC (including 35 in stage I, 14 in stage II, 35 in stage III, and 25 in stage IV) and 104 healthy volunteers matched for age, presenting for a routine physical examination. We analyzed the difference in serum metabolism between GC patients and healthy people through a comparative study of the average Raman spectra of the two groups. Four machine learning methods, one-dimensional convolutional neural network, random forest, support vector machine, and K-nearest neighbor were used to explore identifying two sets of Raman spectral data. The classification model was established by using 70% of the data as a training set and 30% as a test set. Using unseen data to test the model, the RF model yielded an accuracy of 92.8%, and the sensitivity and specificity were 94.7% and 90.8%. The performance of the RF model was further confirmed by the receiver operating characteristic (ROC) curve, with an area under the curve (AUC) of 0.9199. This exploratory work shows that serum Raman spectroscopy combined with RF has great potential in the machine-assisted classification of GC, and is expected to provide a non-destructive and convenient technology for the screening of GC patients.

Molecule-Specific Terahertz Biosensors Based on an Aptamer Hydrogel-Functionalized Metamaterial for Sensitive Assays in Aqueous Environments.

Metamaterial-inspired terahertz (THz) biosensors are devoted to developing high-sensitivity and label-free biosensing strategies. However, most meaningful molecular signals are obscured by the strong THz absorption of solvent water. Most reported THz biosensors require the tested samples to be tediously dried or replaced with a low-absorption medium, which impairs the original bioactivity and the distribution homogeneity of targets. As described in this proposed strategy, a molecule-specific THz biosensor was fabricated from an aptamer hydrogel-functionalized THz metamaterial. Benefitting from the strong interaction with the localized electric field of the metamaterial, trace thrombin-induced variations in the hydration state of the hydrogel can be sensitively probed, which was investigated experimentally and theoretically. The optimized THz biosensor exhibited remarkable specificity for actual serum sample assays and excellent sensitivity, with a relatively low detection limit of 0.40 pM in the human serum matrix. The proposed strategy could serve as a model system to develop various molecule-specific THz biosensors for aqueous molecule sensing.

Streptavidin-functionalized terahertz metamaterials for attomolar exosomal microRNA assay in pancreatic cancer based on duplex-specific nuclease-triggered rolling circle amplification.

Exosomal microRNA (miRNA) is a promising non-invasive biomarker for liquid biopsies. Herein, we fabricated a terahertz (THz) metamaterial biosensor that comprises an array of gold (Au) discs surrounded by annular grooves for exosomal miRNA assays based on duplex-specific nuclease (DSN)-triggered rolling circle amplification (RCA). In this strategy, the target miRNA is captured by a probe P0 immobilized on magnetic beads (MBs); it then repeatedly releases a primer P1 under the action of DSN, which acts as a highly specific initiator of the subsequent RCA step utilizing biotin-dUTP. After target recycling and nucleic acid amplification, the biotinylated amplification products were captured by the streptavidin (SA)-functionalized THz metamaterials, and further conjugated to SA-modified AuNPs that permit formation of a trimeric complex of SA-biotinylated RCA products-AuNP. The complex population scales with the starting concentration of the target miR-21, resulting in a red shift of the resonance peak of the THz metamaterials. This biosensor can lead to highly specific and sensitive detection with one-base mismatch discrimination and a limit of detection (LOD) down to 84 aM. Significant distinctions are seen in the frequency shifts for exosomal miR-21 quantitation in clinical plasma samples between pancreatic cancer patients and healthy controls. The frequency shifts of the THz metamaterials are consistent versus the reverse transcription-polymerase chain reaction (RT-PCR) results, illustrating the applicability and accuracy of our assay in real clinical samples.

miR-135b levels in the peripheral blood serve as a marker associated with acute ischemic stroke.

The protective role of microRNA (miR)-135b in cerebral neurons has been previously identified. However, to the best of our knowledge, the involvement of miR-135b in acute ischemic stroke has yet to be elucidated. The present study aimed to investigate the expression profile of miR-135b in peripheral blood obtained from patients with acute ischemic stroke. A total of 76 patients with acute ischemic stroke were selected as the case group, which included 33 cases of aorta atheromatous plague, 19 cases of cardioembolism, 16 cases of small arterial occlusion and 8 cases with unknown causes. In addition, 60 healthy subjects were selected as the control group. Reverse transcription-quantitative PCR was used to measure the expression of miR-135b in the peripheral blood of the patients. The National Institutes of Health Stroke Scale (NIHSS) score was used to evaluate the severity of acute ischemic stroke. The relationship between miR-135b levels and acute stroke was subsequently analyzed. The expression of miR-135b in the peripheral blood of the case group was found to be significantly higher compared with that in the control group. By contrast, the expression levels of miR-135b in the case group did not differ significantly between the different etiology types of acute ischemic stroke. In addition, a significant positive correlation was observed between levels of miR-135b expression and NIHSS scores. Further analysis demonstrated that hypertension, hyperglycemia, platelet count, international normalized ratio and miR-135b were risk factors for acute ischemic stroke. Based on bioinformatics analysis, a conserved binding site for miR-135b was identified in the 3'-untranslated region of the transient receptor potential cation channel subfamily C member 6 (TRPC6). Dual luciferase reporter and western blot analysis showed that TRPC6 was a target gene of miR-135b. In conclusion, data from the present study suggest that elevated expression of miR-135b in the peripheral blood of patients with acute ischemic stroke is closely associated with disease severity.

Formation and characterization of zein-propylene glycol alginate-surfactant ternary complexes: Effect of surfactant type.

In this study, zein, propylene glycol alginate (PGA) and surfactant ternary complexes were fabricated by antisolvent co-precipitation method. Two types of surfactants (rhamnolipid and lecithin) were applied to generate zein-PGA-rhamnolipid (Z-P-R) and zein-PGA-lecithin (Z-P-L) ternary complexes, respectively. Results showed that the surfactant types significantly affected the properties of ternary complexes. The formation of ternary complexes was mainly due to the non-covalent interactions such as hydrogen bonding, electrostatic interaction and hydrophobic interactions among zein, PGA and surfactants. Moreover, the thermal stability of ternary complexes was enhanced with increasing the levels of both surfactants. Notably, ternary complex dispersions exhibited better stability against pH from 2 to 8. Furthermore, a compact network structure was observed in Z-P-R ternary complex, while Z-P-L ternary complex remained the spherical structure. These findings would provide new insights into the development of novel delivery system and expand the options, when zein-based complexes were utilized under different environment conditions.