Cold Pressing of Perovskite-ZIF Glass Interpenetrating Networks with Stable Photoelectric Response.

The protection of lead halide perovskite within a stable matrix normally leads to the loss of semiconducting properties. Here, we report the synthesis of perovskite-ZIF glass interpenetrating networks via a cold pressing method, which allows the advantages of bright photoluminescence, high photoconductivity and environmental stability. This hybrid architecture has provided a novel design strategy for the real-world application of perovskite-based devices.

Development of [18F]Thiazolylacylaminopyridine-Based Glycogen synthase Kinase-3ß ligands for positron emission tomography imaging.

Glycogen synthase kinase-3ß (GSK-3ß) regulates numerous of CNS-specific signaling pathways, and is particularly implicated in various pathogenetic mechanisms of Alzheimer's disease (AD). A noninvasive method for detecting GSK-3ß in AD brains via positron emission tomography (PET) imaging could enhance the understanding of AD pathogenesis and aid in the development of AD therapeutic drugs. In this study, an array of fluorinated thiazolyl acylaminopyridines (FTAAP) targeting GSK-3ß were designed and synthesized. These compounds showed moderate to high affinities (IC50 = 6.0 - 426 nM) for GSK-3ß in vitro. A potential GSK-3ß tracer, [18F]8, was successfully radiolabeled. [18F]8 had unsatisfactory initial brain uptake despite its suitable lipophilicity, molecular size and good stability. Further structural refinement of the lead compound is needed to develop promising [18F]-labeled radiotracers for the detection of GSK-3ß in AD brains.

Design, Synthesis, and Evaluation of 18F-Labeling CYP1B1 PET Tracer Based on 2-Phenylquinazolin.

Cytochrome P450 (CYP)1B1 has been identified to be specifically overexpressed in several solid tumors, thus it's a potential target for the detection of tumors. Based on the 2-Phenylquinazolin CYP1B1 inhibitors, we designed and synthesized several positron emission computed tomography (PET) imaging probes targeting CYP1B1. Through IC50 determinations, most of these probes exhibited good affinity and selectivity to CYP1B1. Considering their affinity, solubility, and their 18F labeling methods, we chose compound 5c as the best candidate. The 18F radiolabeling of [18F] 5c was easy to handle with good radiolabeling yield and radiochemical purity. In vitro and in vivo stability study indicated that probe [18F]5c has good stability. In cell binding assay, [18F]5c could be specifically taken up by tumor cells, especially HCT-116 cells. Although the tumor-blood (T/B) and tumor-muscle (T/M) values and PET imaging results were unsatisfied, it is still possible to develop PET probes targeting CYP1B1 by structural modification on the basis of 5c in the future.

Hybrid Fiber-Optic Sensing Integrating Brillouin Optical Time-Domain Analysis and Fiber Bragg Grating for Long-Range Two-Parameter Measurement.

Distributed fiber sensing (DFS) can provide real-time signals and warnings. The entire length of fiber optic cable can act as a sensing element, but the accuracy is sometimes limited. On the other hand, point-to-point fiber sensing (PPFS) is usually implemented using one or more fiber Bragg gratings (FBGs) at specific positions along with the fiber for the monitoring of specific parameters (temperature, strain, pressure, and so on). However, the cost becomes expensive when the number of FBGs increases. A hybrid fiber sensing scheme is thus proposed, combining the advantages of DFS and PPFS. It is based on a Brillouin optical time-domain analysis (BOTDA) fiber system with additional FBGs embedded at certain positions where it is necessary to detect specific parameters. The hybrid fiber sensing system has the advantages of full sensing coverage at essential locations that need to be carefully monitored. In our work, the test results showed that the proposed system could achieve a sensing distance of 16 km with the single-mode fiber with a 2 m spatial resolution. For FBG parameter measurements, the temperature variation was 52 °C, from 25 °C to 77 °C, with a temperature sensitivity of 23 pm/°C, and the strain was from 0 to 400 µÎµ, with a strain sensitivity of 0.975 pm/µÎµ, respectively, using two FBGs.

Docetaxel-Loaded Lecithoid Nanoparticles with Enhanced Lung Targeting Efficiency and Reduced Systemic Toxicity: Developed by Solid Dispersion and Effervescent Techniques.

The application of chemotherapeutics with chemical drugs is always challenged by their high toxicities throughout the body in clinical trials. Here, we reported a smart formulation of docetaxel developed by solid dispersion and effervescent techniques for efficient and safe delivery of chemical drug to lung tissue. To achieve a high delivery to lung with reduced systemic toxicity, docetaxel was loaded into a kind of lecithoid nanoparticles (DTX-LN) which were prepared by a solid dispersion and effervescent method. After intravenous administration of DTX-LN to rabbit, the docetaxel level in lung was approximately 37-fold higher than that of docetaxel injection (DTX-INJ, a commercial injection preparation of DTX/polysorbate 80 micelles) group at 0.5 h and showed the highest tissue distribution among all the organs. Besides, the targeting parameter Re value of total increased amount of DTX in lung (AUC0-t) ratio (DTX-LN to DTX-INJ) is about 16.69, indicating a significantly enhanced lung targeting ability of DTX-LN. In subacute toxicity study, DTX-LN displayed a reduced hematotoxicity, especially for the negative impacts on white blood cells, lymphocyte and granulocyte when compared with DTX-INJ during both weekly and 3-weekly schedules administration. In addition, histopathological analysis demonstrated that DTX-LN showed less tissue damages on rabbit heart and kidney compared to DTX-INJ. Hence, this work would provide an insight for improving lung delivery efficacy of drugs with reduced systemic toxicity.

Characterization of molecular channel in photodissociation of SOCl2 at 248 nm: Cl2 probing by cavity ring-down absorption spectroscopy.

A primary elimination channel of the chlorine molecule in the one-photon dissociation of SOCl2 at 248 nm was investigated using cavity ring-down absorption spectroscopy (CRDS). By means of spectral simulation, the ratio of the vibrational population in the v = 0, 1, and 2 levels was evaluated to be 1 : (0.10 ± 0.02) : (0.009 ± 0.005), corresponding to a Boltzmann vibrational temperature of 340 ± 30 K. The Cl2 molecular channel was obtained with a quantum yield of 0.4 ± 0.2 from the X(1)A' ground state of SOCl2via internal conversion. The dissociation mechanism differs from a prior study where a smaller yield of <3% was obtained, initiated from the 2(1)A' excited state. Temperature-dependence measurements of the Cl2 fragment turn out to support our mechanism. With the aid of ab initio potential energy calculations, two dissociation routes to the molecular products were found, including one synchronous dissociation pathway via a three-center transition state (TS) and the other sequential dissociation pathway via a roaming-mediated isomerization TS. The latter mechanism with a lower energy barrier dominates the dissociation reaction.

Clinical value of 68Ga-pentixafor PET/CT in patients with primary aldosteronism and bilateral lesions: preliminary results of a single-centre study.

BACKGROUND: Subtype diagnosis of primary aldosteronism (PA) is used to determine treatment, and the potential utility of 68Ga-pentixafor PET/CT for investigation of PA has long been recognized. The study aimed to evaluate the clinical value of 68Ga-pentixafor PET/CT in the diagnosis and prognosis of patients with bilateral lesions identified by CT. METHODS: In total, 25 patients with PA and bilateral lesions on CT were retrospectively evaluated. All patients underwent 68Ga-Pentixafor PET/CT and adrenal vein sampling. The analysis focused on establishing the relationship between bilateral adrenal lesions SUVmax and the ratio of bilateral adrenal lesions SUVmax (CON) and clinical diagnosis, treatment outcomes, and KCNJ5 gene status. RESULTS: The concordance rate between 68Ga-Pentixafor PET/CT and adrenal venous sampling was 65.2% (15/23). The lateralization results of 68Ga-pentixafor PET/CT supported the clinical decisions of 20 patients with PA, 90% of whom showed effectiveness in treatment. The SUVmax on the dominant side of the surgically treated patients was higher than that of patients treated with drugs. The SUVmax of the KCNJ5 mutant group was higher than that of the KCNJ5 wild group, and 68Ga-Pentixafor uptake was correlated with KCNJ5 gene status. CONCLUSIONS: 68Ga-Pentixafor PET/CT proves beneficial for patients with PA with bilateral lesions on CT. The treatment is generally effective based on the results of PET lateralization. Simultaneously, a certain relationship exists between 68Ga-Pentixafor PET/CT and KCNJ5 gene status, warranting further analysis.

Accuracy of death risk prediction models for acute coronary syndrome patients: a systematic review and meta-analysis.

INTRODUCTION: This study systematically evaluates the accuracy of several death risk prediction models for patients with acute coronary syndrome (ACS) through evidence-based methods. We identify the most accurate and effective ACS death risk prediction model and provide an evidence-based basis for clinical healthcare personnel to evaluate their choice of death risk prediction model for ACS patients. EVIDENCE ACQUISITION: An evidence-based approach was used to study the current death risk prediction model for ACS. First, a literature search was carried out using computer-based and manual searching. The literature databases searched include Cochrane Library, MEDLINE, EMBASE, PubMed, Web of Science, WanFang Data, CNKI, VPCS, and SinoMed. The search period was limited to 2009 to 2022. Screening, quality evaluation and data extraction were carried out for the included articles. The PROBAST was used to conduct a migration risk assessment. RevMan 5.3 and Meta-DiSc 1.4 were used in combination to determine the model effect sizes. A descriptive analysis was conducted for the data that could not be meta-analyzed. EVIDENCE SYNTHESIS: A total of 8277 articles were initially included in this study. After screening, 25 articles were finally included, involving 11 different risk prediction models. A total of 306,390 patients with ACS were included of which 158,080 (51.6%) were male and 147,793 (48.4%) were female. The patients stemmed from 11 different countries (e.g., China, the USA, Spain, the UK, etc.). The total number of deaths was 23,601. The sensitivity of the GRACE risk prediction model was 0.78, with a specificity of 0.76 and an AUC value of 0.86. The sensitivity of the CAMI risk prediction model was 0.78, with a specificity of 0.70 and an AUC value of 0.85. The sensitivity of the TIMI risk prediction model was 0.51, with a specificity of 0.81, and an AUC value of 0.64. The sensitivity of the REMS risk prediction model was 0.78, with a specificity of 0.46 and an AUC value of 0.41. Eight different risk prediction models (EPICOR, CRUSADE, SAMI, GWTG, LNS, SYNTAX II, APACHE II) that could not be combined with the effect size were also included, with sensitivities ranging from 0.77-0.95, specificities ranging from 0.22-0.99, and AUC values ranging from 0.71-0.92. CONCLUSIONS: The GRACE and CAMI risk prediction models demonstrate good accuracy for evaluating the death risk of ACS patients. The accuracy of the TIMI risk prediction model is similar to that of the REMS risk prediction model. The APACHE II, SYNTAX II, EPICOR, and CAMI risk prediction models also show good accuracy for estimating the risk of death in ACS patients, although further validation is needed due to limited evidence. For improved predictive accuracy and to help advance medical interventions, the author recommends that clinical medical staff use the GRACE model to predict the death risk of ACS patients.

Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing.

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.

Vanadium complexes bearing 8-anilide-5,6,7-trihydroquinoline ligands for ethylene (co-)polymerization.

Several trivalent and pentavalent vanadium complexes bearing 8-anilide-5,6,7-trihydroquinoline ligands were synthesized. These vanadium complexes were identified by elemental analysis, FTIR spectroscopy and NMR. Single crystals of trivalent vanadium complexes V2, V3', and V4 and pentavalent vanadium complexes V5 and V7 were further obtained and identified by X-ray single crystal diffraction. In addition, the catalytic performance of these catalysts was adjusted by controlling the electronic and steric effects of substituents in the ligands. In the presence of diethylaluminium chloride, complexes V5-V7 displayed high activity (up to 82.8 × 106 g molV-1 h-1) and good thermal stability toward ethylene polymerization. In addition, the copolymerization ability of complexes V5-V7 was evaluated, and complexes V5-V7 displayed high activity (up to 105.6 × 106 g molV-1 h-1) and high copolymerization ability toward ethylene/norbornene copolymerization. By adjusting the polymerization conditions, copolymers with norbornene insertion ratios of 8.1%-30.9% can be obtained. Complex V7 was further studied for ethylene/1-hexene copolymerization, and the obtained copolymer displayed a moderate 1-hexene insertion ratio of 1.2%. Complex V7 displayed high activity and high copolymerization ability while having thermal stability. The results showed that 8-anilide-5,6,7-trihydroquinoline ligands with fused rigid-flexible rings were beneficial for vanadium catalysts.

Maresin-1 improves LPS-induced depressive-like behavior by inhibiting hippocampal microglial activation.

Maresin-1 is an antiphlogistic agonist synthesized by macrophages from docosahexaenoic acid (DHA). It has both anti-inflammatory and pro-inflammatory properties and has been found to enhance neuroprotection and cognitive function. However, there is limited knowledge of its effects on depression and the potential mechanism remains unclear. In this study, the effects of Maresin-1 on lipopolysaccharide (LPS)-induced depressive symptoms and neuroinflammation were investigated in mice and the possible cellular and molecular mechanisms were further clarified. Maresin-1 treatment (5 µg/kg, i.p.) led to improved tail suspension times, as well as distances moved in an open-field test but it did not improve reductions in sugar-water consumption in mice with depressive-like behaviors induced by LPS (1 mg/kg, i.p.); TSPO PETCT scanning showed that Maresin-1 reduced the standardized uptake value (SUV) of [18 F] DPA-714 in brain regions associated with depression (e.g., hippocampus and pre-frontal cortex), while immunofluorescence of hippocampal and indicated that Maresin-1 inhibited microglial activation reducing the expression of the pro-inflammatory cytokine IL-1ß and NLRP3. The RNA sequencing of mouse hippocampi showed that genes expressed differentially between Maresin-1-treated and LPS-treated tissue were associated with tight connections between cells and the stress-activated MAPK cascade negative regulatory pathways. Overall, this study demonstrates that peripheral application of Maresin-1 could partially relieve LPS-induced depressive-like behaviors and showed for the first time that this effect was related to its anti-inflammatory action on microglia, thus providing new clues for the pharmacological mechanism underlying the anti-depression properties of Maresin-1.

Clinical application of 18F-FCH PET/CT in the diagnosis and treatment of hyperparathyroidism.

Objective: We evaluated the difference in parathyroid visualization on 18F-FCH PET/CT images obtained at 5 and 60 min, and quantitatively analyzed the mode of FCH uptake at different time points, to determine the best imaging time for FCH PET/CT. Methods: This retrospective study included 73 patients with hyperparathyroidism (HPT) who underwent 18F-FCH PET/CT imaging between December 2017 and December 2021. The diagnostic efficiency of 5- and 60-min dual time point imaging for the diagnosis of hyperparathyroidism and parathyroid adenoma and hyperplasia, were compared using visual and quantitative analyses. Results: Dual-time 18F-FCH PET/CT imaging visual analysis had diagnostic value for HPT. The receiver operating characteristic curve of PET/CT quantitative parameters for the diagnosis of HPT and lesions showed that the parathyroid/thyroid SUVmax ratio for 60-min imaging had a higher sensitivity and specificity (based on patient, sensitivity: 90.90% and specificity: 85.71%; based on focus, sensitivity: 83.06% and specificity: 85.71%) compared to that for 5-min imaging. PET/CT quantitative parameters can distinguish parathyroid adenoma and hyperplasia. The 60-min parathyroid SUVmax value had the highest diagnostic value (cutoff: 3.945; area under the curve: 0.783). Conclusion: The quantitative parameters of 60min 18F-FCH PET/CT have more advantages in aiding in the pathologica diagnosis and clinical treatment of HPT.

The clinical signification and application value of [68Ga]Ga-PSMA imaging in thyroid malignancy.

PURPOSE: Approximately 5% of differentiated thyroid cancers lose the ability to uptake iodine, leading to limited treatment options and poor prognosis due to invasion and distant metastasis. PSMA imaging probes have been proposed as a potential diagnostic and therapeutic tool for iodine-refractory thyroid cancer. However, there are limited reports and significant heterogeneity in patient selection, warranting further exploration of the application value of PSMA in thyroid cancer. METHODS: We performed Western Blot, PCR, and [68Ga]Ga-PSMA uptake experiments on cell lines and conducted in vivo small animal imaging. Clinical and radiological results of included differentiated thyroid cancer patients were collected. (Trial registration number: 2021-669, Trial registration date: December 30, 2021). RESULTS: PSMA expression levels were significantly higher in poorly differentiated thyroid cancer (7.86 ± 1.90 vs. 1.00 ± 0, P < 0.01; 7.86 ± 1.90 vs. 0.03 ± 0.02, P < 0.01), but [68Ga]Ga-PSMA imaging correlated with tumor burden, such as 18F-FDG (8.08 ± 7.74 and 5.67 ± 4.23, P = 0.01) and Tg levels (307.1 ± 183.4 vs. 118.0 ± 116.1, P = 0.002). CONCLUSION: Our results showed that PSMA expression increased with the decrease of thyroid cancer differentiation. However, the level of [68Ga]Ga-PSMA uptake in thyroid cancer patients was not significantly associated with the degree of thyroid cancer differentiation, but also with the metabolism and burden of tumors such as 2-[18F]FDG and Tg levels. These findings provide additional clinical significance and application value for PSMA in thyroid cancer.

A Runx2/miR-3960/miR-2861 regulatory feedback loop during mouse osteoblast differentiation.

Our recent study showed that miR-2861 promotes osteoblast differentiation by targeting histone deacetylase 5, resulting in increased runt-related transcription factor 2 (Runx2) protein production. Here we identified another new microRNA (miRNA) (miR-3960) that played a regulatory role in osteoblast differentiation through a regulatory feedback loop with miR-2861. miR-3960 and miR-2861 were found clustered at the same loci. miR-3960 was transcribed during bone morphogenic protein 2 (BMP2)-induced osteogenesis of ST2 stromal cells. Overexpression of miR-3960 promoted BMP2-induced osteoblastogenesis. However, the inhibition of miR-3960 expression attenuated the osteoblastogenesis. Homeobox A2 (Hoxa2), a repressor of Runx2 expression, was confirmed to be a target of miR-3960. Electrophoretic mobility shift assay and chromatin immunoprecipitation experiments confirmed that Runx2 bound to the promoter of the miR-3960/miR-2861 cluster. Furthermore, overexpression of Runx2 induced miR-3960/miR-2861 transcription, and block of Runx2 expression attenuated BMP2-induced miR-3960/miR-2861 transcription. Here we report that miR-3960 and miR-2861, transcribed together from the same miRNA polycistron, both function in osteoblast differentiation through a novel Runx2/miR-3960/miR-2861 regulatory feedback loop. Our findings provide new insights into the roles of miRNAs in osteoblast differentiation.

Dynamic microglial activation is associated with LPS-induced depressive-like behavior in mice: An [18F] DPA-714 PET imaging study.

Major depressive disorder (MDD) is a highly pervasive, severe psychological condition for which the precise underlying pathophysiology is incompletely understood, although microglial activation is known to play a role in this context. In this study we analyzed the association between neuroinflammation and depressive-like behaviors in a lipopolysaccharide (LPS)-induced mouse model system using 10-12-week-old male C57BL/6 mice. Microglial activation and associated neuroinflammatory activity were monitored via positron emission tomography (PET) imaging. Animals were assessed at three time points, including 24 h prior to LPS injection, 24 h post-LPS injection, and 72 h post-LPS injection. Analyses of microglial activation and hippocampal neuroinflammation were conducted through [18]F DPA-714 PET imaging and immunohistochemical staining for ionized calcium-binding adapter molecule 1 (Iba-1) and translocator protein (TSPO). Moreover, NOD-like receptor protein 3 (NLRP3) inflammasome activity and interleukin-1ß (IL-1ß) levels were assessed at 24 h post-LPS injection. We found that LPS treatment was associated with a marked increase in depressive-like behavior at 24 h post-injection time point, and that it was less pronounced at the 72 h post-injection time point. These changes coincided with enhanced [18F] DPA-714 PET uptake in the whole brain, hippocampus, cortex and amygdala together with increased hippocampal microglial activation as evidenced by immunofluorescent staining. By 72 h post-injection, however, these PET and immunofluorescence phenotypes had returned to baseline levels. Furthermore, increased NLRP3 inflammasome activation and IL-1ß expression were evident at 24 h post-LPS injection. These data demonstrate that dynamic microglial activation is associated with LPS-induced depressive-like behaviors and hippocampal neuroinflammation in a mouse model system.

Microglia Loss and Astrocyte Activation Cause Dynamic Changes in Hippocampal [18F]DPA-714 Uptake in Mouse Models of Depression.

Major depression is a serious and chronic mental illness. However, its etiology is poorly understood. Although glial cells have been increasingly implicated in the pathogenesis of depression, the specific role of microglia and astrocytes in stress-induced depression remains unclear. Translocator protein (TSPO) has long been considered a marker of neuroinflammation and microglial activation. However, this protein is also present on astrocytes. Thus, it is necessary to explore the relationships between TSPO, microglia, and astrocytes in the context of depression. In this study, C57BL/6J male mice were subjected to chronic unpredictable stress (CUS) for 5 weeks. Subsequently, sucrose preference and tail suspension tests (TSTs) were performed to assess anhedonia and despair in these mice. [18F]DPA-714 positron emission tomography (PET) was adopted to dynamically assess the changes in glial cells before and 2, 4, or 5 weeks after CUS exposure. The numbers of TSPO+ cells, ionized calcium-binding adaptor molecule (Iba)-1+ microglial cells, TSPO+/Iba-1+ cells, glial fibrillary acidic protein (GFAP)+ astrocytes, TSPO+/GFAP+ cells, and TUNEL-stained microglia were quantified using immunofluorescence staining. Real-time PCR was used to evaluate interleukin (IL)-1ß, IL-4, and IL-18 expression in the hippocampus. We observed that hippocampal [18F]DPA-714 uptake significantly increased after 2 weeks of CUS. However, the signal significantly decreased after 5 weeks of CUS. CUS significantly reduced the number of Iba-1+, TSPO+, and TSPO+/Iba-1+ cells in the hippocampus, especially in the CA1 and dentate gyrus (DG) subregions. However, this intervention increased the number of GFAP+ astrocytes in the CA2/CA3 subregions of the hippocampus. In addition, microglial apoptosis in the early stage of CUS appeared to be involved in microglia loss. Further, the expression of pro-inflammatory cytokines (IL-1ß and IL-18) was significantly decreased after CUS. In contrast, the expression of the anti-inflammatory cytokine IL-4 was significantly increased after 2 weeks of CUS. These results suggested that the CUS-induced dynamic changes in hippocampal [18F]DPA-714 uptake and several cytokines may be due to combined microglial and astrocyte action. These findings provide a theoretical reference for the future clinical applications of TSPO PET.

Parathyroid hormone alleviates non-alcoholic liver steatosis via activating the hepatic cAMP/PKA/CREB pathway.

Non-alcoholic fatty liver disease (NAFLD), hallmarked by liver steatosis, is becoming a global concern, but effective and safe drugs for NAFLD are still lacking at present. Parathyroid hormone (PTH), the only FDA-approved anabolic treatment for osteoporosis, is important in calcium-phosphate homeostasis. However, little is known about its potential therapeutic effects on other diseases. Here, we report that intermittent administration of PTH ameliorated non-alcoholic liver steatosis in diet-induced obese (DIO) mice and db/db mice, as well as fasting-induced hepatic steatosis. In vitro, PTH inhibits palmitic acid-induced intracellular lipid accumulation in a parathyroid hormone 1 receptor (PTH1R)-dependent manner. Mechanistically, PTH upregulates the expression of genes involved in lipid ß-oxidation and suppresses the expression of genes related to lipid uptake and de novo lipogenesis by activating the cAMP/PKA/CREB pathway. Taken together, our current finding proposes a new therapeutic role of PTH on NAFLD.

Renewable Vanillin-Based Thermoplastic Polybutadiene Rubber: High Strength, Recyclability, Self-Welding, Shape Memory, and Antibacterial Properties.

The vast majority of traditional vulcanized rubber products are insoluble and infusible, which is difficult to reprocess and biodegrade, resulting in black pollution. In addition, although most rubber materials based on covalent adaptive networks (CANs) can achieve structural reconstruction, the lack of traditional vulcanization system leads to a decline in strength. In this study, biobased vanillin derivatives (PV) were synthesized to cross-link the commercially available 1,2-polybutadiene rubber precursor to construct imine-based CANs, thereby fabricating a resource-renewable, recyclable, and degradable high-performance rubber material. Due to the rigid tripod structure of the PV, the tensile strength of the material can achieve as high as 16.24 MPa, ranking among the best in the field of recyclable polybutadiene-based materials. Benefiting from the dynamic imine unit, the "dynamic covalent bridge" can be re-established to repair the damaged network and endow the material with excellent weldability. And, shape memory faculty of the material was proved and depicted. Moreover, this material displayed excellent antibacterial property originates from the introduced Schiff-base structure. By mixing with graphene, the application of action sensors can also be achieved.

Dihydrosanguinarine based RNA-seq approach couple with network pharmacology attenuates LPS-induced inflammation through TNF/IL-17/PI3K/AKT pathways in mice liver.

Dihydrosanguinarine (DS) is one of the main chemical constituents of Corydalis bungeana Turcz. which demonstrates anti-inflammatory, antioxidant, and antimicrobial in vitro. The present study aimed to investigate the anti-inflammatory effect and its underlying mechanism of DS in vivo. The network pharmacology method was used to predict the anti-inflammatory target of DS, and it was found that PI3K-AKT signal transduction pathway was the most obvious, and the anti-inflammatory effect of DS was more specific in liver. Herein, we used AKT inhibitor AZD 5363 to block PI3K-AKT signaling pathway, to carry out animal experiments to verify the predicted results of network pharmacology. The results showed that DS exerts protective effects on LPS-induced liver inflammation in mice, and the anti-inflammatory effect of DS was attenuated after inhibiting AKT. To elucidate the potential molecular mechanisms, we performed RNA-sequence analysis in liver tissues. Transcriptome analysis showed that the "TNF signaling pathway" and "IL-17 signaling pathway" had the highest enrichment of differentially expressed genes (DEGs). Then, TNF/IL-17/PI3K-AKT signal pathways were analyzed by GSEA. It was found that AKT3, CCL2, FOS, IL-17A, IL-17RA, IL-17RE, PI3KCA, TRAF3IP2, CREB5, ICAM-1, VCAM-1, IL-1ß, IL-6, TNF-α and CXCL1/2/3 were significantly regulated by DS. The results of RNA-seq immuneCC predictive showed that DS could inhibit the inflammatory response mainly by reducing the degree of macrophage infiltration induced by LPS. At the same time, we use RT-qPCR, IF, WB techniques to verify the core anti-inflammatory differential genes of DS at the gene and protein expression level, confirming that DS can regulate the inflammatory response by regulating the gene expression level of TNF/IL-17/PI3K-AKT signal pathway. We also used HPLC-Q-TOF/MS technology to explore the biotransformation products of DS in the blood and liver of mice under inflammatory conditions and established the docking model of DS and its transformed compound with TNF-α, IL-17A, AKT3 and IL-6, which is the key target from RNA-seq analysis in this study. The results showed that DS strongly interacted with four proteins in the form of prototypes and demethylated products and exhibited anti-inflammatory effects. Our research shows that DS exerts its anti-hepatitis effect mainly by inhibiting the excessive infiltration of macrophages in mice liver induced by LPS and down-regulating the expression of genes related to TNF/IL-17/PI3K-AKT pathway. This study provides a new perspective on the potential therapeutic application of DS and the plasticity of anti-LPS-induced liver inflammation in DS.

Scara3 regulates bone marrow mesenchymal stem cell fate switch between osteoblasts and adipocytes by promoting Foxo1.

OBJECTIVES: Scavenger receptor class A, member 3 (Scara3) was involved in adipogenesis. However, the effect of Scara3 on the switch between osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) remains elusive. MATERIALS AND METHODS: The correlations between SCARA3 with the osteogenic-related were analysed based on the GTEx database. The effects of Scara3 on osteogenic or adipogenic differentiation of BMSCs were evaluated by qPCR, Western blot (WB) and cell staining. The mechanisms of Scara3 regulating Foxo1 and autophagy were validated by co-expression analysis, WB and immunofluorescence. In vivo, Scara3 adeno-associated virus was injected into intra-bone marrow of the aged mice and ovariectomized (OVX) mice whose phenotypes were confirmed by micro-CT, calcein double labelling and immunochemistry (HE and OCN staining). RESULTS: SCARA3 was positively correlated with osteogenic-related genes. Scara3 expression gradually decreased during adipogenesis but increased during osteogenesis. Moreover, the deletion of Scara3 favoured adipogenesis over osteogenesis, whereas overexpression of Scara3 significantly enhanced the osteogenesis at the expense of adipogenesis. Mechanistically, Scara3 controlled the cell fate by promoting Foxo1 expression and autophagy flux. In vivo, Scara3 promoted bone formation and reduced bone marrow fat accumulation in OVX mice. In the aged mice, Scara3 overexpression alleviated bone loss as well. CONCLUSIONS: This study suggested that Scara3 regulated the switch between adipocyte and osteoblast differentiation, which represented a potential therapeutic target for bone loss and osteoporosis.