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The growing impact of the built environment on the natural environment, human health, and its economic importance has emphasized the importance of green building design. It is widely recognized that the most significant benefits can be obtained if the green design initiatives can be implemented at the earliest stages of the design processes. This requires designers to consider embodied impacts (embodied energy and emission) among other criteria in selecting building systems and materials during the early design phase of a building. However, this endeavor is not a simple task, as the absence of appropriate tools to facilitate such considerations becomes apparent. The aim of this research is to develop an innovative system, which can support designers in selecting the structure and envelope systems of a building considering the embodied impacts and costs during the early design stage. A graphical user interface empowers designers to scrutinize diverse building structures and exterior envelope assemblies and compare their embodied energy, embodied carbon emissions, and costs, thereby making an informed decision about the most desirable systems. To validate its utility, a case study is used to illustrate the application of the system and demonstrate the feasibility of its use in selecting structure and envelope systems for educational buildings. [ABSTRACT FROM AUTHOR]

Tumor metastasis is responsible for 90% of cancer-associated deaths, and its early detection may decrease the likelihood of mortality. Studies have demonstrated that metastasis results from the interaction between "seeds" (tumor cells) and "soil" (pre-metastatic niche, PMN). As the first and most abundant immune cells to be recruited to PMN, neutrophils play a key role in the ultimate formation of metastatic foci through mechanisms such as supporting tumor cell growth, promoting angiogenesis, and shaping an immune-suppressive microenvironment. In this study, two distinct types of sialic acid (SA)-modified liposomes were prepared to target and regulate pro-metastatic neutrophils through the l -selectin receptor. One of these liposomes, named ICG@SAL, was used to encapsulate indocyanine green (ICG) and was specifically designed for the early detection of cancer metastasis. The other liposome, referred to as ABE/Cur@SAL, co-loaded abemaciclib (ABE) and curcumin (Cur), with the intention of suppressing the progression of metastatic tumor. Fluorescence imaging results from the mouse spontaneous metastasis model indicated that ICG@SAL demonstrated faster targeting and stronger accumulation in the metastatic organs than unmodified ICG liposomes (ICG@CL). This suggested that ICG@SAL could detect tumor metastasis at an early stage. The therapy with co-loaded liposomes in the mouse experimental lung metastasis model indicated that ABE/Cur@SAL could inhibit regulatory T (Treg) cell proliferation, enhance effector T cell activity and reduce tumorigenic factor release, implying that ABE/Cur@SAL could inhibit tumor metastasis. Overall, our work provided a sensitive and convenient approach to early diagnosis and treatment of tumor metastasis. ICG@SAL could be employed for the early detection of tumor metastasis, while ABE/Cur@SAL could be used to inhibit the development of tumor metastasis when early metastasis was identified. [ABSTRACT FROM AUTHOR]

Background: Pulmonary fibrosis (PF) emerges as a significant pulmonary sequelae in the convalescent phase of coronavirus disease 2019 (COVID-19), with current strategies neither specifically preventive nor therapeutic. Licoricesaponin G2 (LG2) displays a spectrum of natural activities, including antibacterial, anti-inflammatory, and antioxidant properties, and has been effectively used in treating various respiratory conditions. However, the potential protective effects of LG2 against PF remain underexplored. Methods: Network analysis and molecular docking were conducted in combination to identify the core targets and pathways through which LG2 acts against PF. In the model of bleomycin (BLM)-induced C57 mice and transforming growth factor-β1 (TGF-β1)-induced A549 and MRC5 cells, techniques such as western blot (WB), quantitative Real-Time PCR (qPCR), Immunohistochemistry (IHC), Immunofluorescence (IF), and Transwell migration assays were utilized to analyze the expression of Epithelial-mesenchymal transition (EMT) and inflammation proteins. Based on the analysis above, we identified targets and potential mechanisms underlying LG2's effects against PF. Results: Network analysis has suggested that the mechanism by which LG2 combats PF may involve the TNF-α pathway. Molecular docking studies have demonstrated a high binding affinity of LG2 to TNF-α and MMP9. Observations from the study indicated that LG2 may mitigate PF by modulating EMT and extracellular matrix (ECM) remodeling. It is proposed that the therapeutic effect is likely arises from the inhibition of inflammatory expression through regulation of the TNF-α pathway. Conclusion: LG2 mitigates PF by suppressing TNF-α signaling pathway activation, modulating EMT, and remodeling the ECM. These results provide compelling evidence supporting the use of LG2 as a potential natural therapeutic agent for PF in clinical trials. [ABSTRACT FROM AUTHOR]

Chalcogen bonding (ChB) interactions have drawn intensive attention in the last few decades as interesting alternatives to hydrogen bonding. The applications of ChB were mostly centered on the solid state and have rarely been explored in solution. In this work, a novel strategy for forming ChB-based deep eutectic solvents (DESs) was exploited. We set forth the formation, physicochemical properties, and interaction sites in detail. This work not only provides a new idea to design DES systems but also to exploit the potential application of ChB complexes. [ABSTRACT FROM AUTHOR]

Drug-resistant Tuberculosis (TB) is a global public health problem. Resistance to rifampicin, the most effective drug for TB treatment, is a major growing concern. The etiological agent, Mycobacterium tuberculosis (Mtb), has a cluster of ATP-binding cassette (ABC) transporters which are responsible for drug resistance through active export. Here, we describe studies characterizing Mtb Rv1217c-1218c as an ABC transporter that can mediate mycobacterial resistance to rifampicin and have determined the cryo-electron microscopy structures of Rv1217c-1218c. The structures show Rv1217c-1218c has a type V exporter fold. In the absence of ATP, Rv1217c-1218c forms a periplasmic gate by two juxtaposed-membrane helices from each transmembrane domain (TMD), while the nucleotide-binding domains (NBDs) form a partially closed dimer which is held together by four salt-bridges. Adenylyl-imidodiphosphate (AMPPNP) binding induces a structural change where the NBDs become further closed to each other, which downstream translates to a closed conformation for the TMDs. AMPPNP binding results in the collapse of the outer leaflet cavity and the opening of the periplasmic gate, which was proposed to play a role in substrate export. The rifampicin-bound structure shows a hydrophobic and periplasm-facing cavity is involved in rifampicin binding. Phospholipid molecules are observed in all determined structures and form an integral part of the Rv1217c-1218c transporter system. Our results provide a structural basis for a mycobacterial ABC exporter that mediates rifampicin resistance, which can lead to different insights into combating rifampicin resistance. [ABSTRACT FROM AUTHOR]

Isotope data of key pollutants are needed for source apportionment analysis in natural ecosystems. Isotope data for cadmium (Cd), a rare and dispersed but toxic element, are very limited mainly due to its low contents in the natural environment. In this study, for samples with low Cd content but high organic matter content, a dry ashing pre-treatment method was proposed to effectively enrich Cd to meet the requirements of its isotope analysis (Cd content > 20 ng). This method was applied to soils, sediments, biological tissues, and coal, with a maximum digestion weight of 1.67 g or more. With the assistance of quartz microfiber filter membranes during dry ashing, good Cd recovery (91.6--108.0%) and significant removal of organic matter were achieved. Mass bias was corrected by combining the silver external standard (Ag-doping) method with the sample-standard-bracketing (SSB) method, and Cd isotope measurements were performed under wet plasma conditions (with an accuracy of 0.060‰). Cd isotopic compositions obtained by the dry ashing method were compared with those obtained by the high-pressure bomb digestion method, and the differences ranged from -0.056 to 0.076‰, indicating that the dry ashing with wrapped membranes method did not cause any fractionation of Cd during the sample pre-treatment process. Meanwhile, the tolerance of tin (Sn) and zinc (Zn) elements provided a significant advantage under wet plasma conditions over dry plasma conditions without reducing the tolerance of molybdenum (Mo) and zirconium (Zr). The method developed in this study should enhance the application of Cd isotopes in investigating Cd cycling in primary ecosystems and organisms. [ABSTRACT FROM AUTHOR]

Predicting nearshore significant wave heights (SWHs) with high accuracy is of great importance for coastal engineering activities, marine and coastal resource studies, and related operations. In recent years, the prediction of SWHs in twodimensional fields based on deep learning has been gradually emerging. However, predictions for nearshore areas still suffer from insufficient resolution and poor accuracy. This paper develops a NS (NearShore) model based on the GWSM4C model (Global Wave Surrogate Model for Climate simulations). In the training area, the GWSM4C -NS model achieved a correlation coefficient (CC) of 0.977, with a spatial Root Mean Square Error (RMSE), annual mean spatial relative error (MAPE), and annual mean spatial absolute error (MAE) of 0.128 m, 10.7%, and 0.103 m, respectively. Compared to the GWSM4C model's predictions, the RMSE and MAE decreased by 59% and 60% respectively, demonstrating the model's effectiveness in enhancing nearshore SWH predictions. Additionally, applying this model to untrained sea areas to further validate its learning capability in wave energy propagation resulted in a CC of 0.951, with RMSE, MAPE, and MAE of 0.161m, 12.9%, and 0.137m, respectively. The RMSE and MAE were 43% and 39% lower than the GWSM4C model's interpolated predictions. The results shown above suggest that the newly proposed model can effectively improve the performance of GWSM4C in nearshore areas. [ABSTRACT FROM AUTHOR]

Lycium barbarum L. (L. barbarum) is an economic crop with high added value and profit. Vibration harvesting is a suitable mechanized harvesting method for L. barbarum. It bruises easily during harvesting due to the softness and vulnerability of fresh ripe fruit, resulting in economic losses. This study analyzed the fruit drop and collision during vibration harvesting. High-speed photography was used to obtain the impact speed and angle of the falling fruit, and a kinematic analysis of the collision with the collection surface was conducted. The majority of the fruit had an impact speed of 3-6 m/s and an impact angle of 30-90° with the collection surface. A drop test was conducted to assess fruit bruising, and the impact speed was converted to the drop height. An orthogonal rotation experiment was conducted, and mathematical model was established between the drop height, impact angle, and impact material, and the fruit bruise rate, maximum impact force, recovery coefficient, and impact time. The effects of the factors on the fruit bruise rate, maximum impact force, recovery coefficient, and impact time were analyzed. The test results show that a vibration harvesting device for L. barbarum should be designed to reduce the height between the fruit and the collection surface and utilize a tilted collection surface and high cushioning materials to reduce the fruit bruising. This study provides guidance for subsequent research on the bruising of L. barbarum during vibration harvesting and harvester design. [ABSTRACT FROM AUTHOR]

Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffoldbased cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemoimmunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors. [ABSTRACT FROM AUTHOR]

Due to the abundance and sustainability of solar energy, converting it into chemical energy to obtain clean energy presents an ideal solution for addressing environmental pollution and energy shortages stemming from the extensive combustion of fossil fuels. In recent years, hydrogen energy has emerged on the stage of history as the most promising clean energy carrier of the 21st century. Among the current methods of producing hydrogen, photocatalytic hydrogen production technology, as a zero-carbon approach to producing high calorific value and pollution-free hydrogen energy, has attracted much attention since its discovery. As the core of photocatalysis technology, semiconductor photocatalysts are always the research hotspots. Among them, graphite-phase carbon nitride (g-C3N4), an organic semiconductor material composed of only C and N elements, possesses physicochemical properties incomparable to those of traditional inorganic semiconductor materials, including suitable energy band positions, easy structural regulation, inexpensive raw materials and abundant reserves, simple preparation, high thermal/mechanical/chemical stability, etc. Therefore, g-C3N4 has attracted extensive attention in the field of photocatalytic hydrogen production in the last two decades. This review comprehensively outlines the research trajectory of g-C3N4 photocatalytic hydrogen production, encompassing development, preparation methods, advantages, and disadvantages. A concise introduction to g-C3N4 is provided, as well as an analysis of the underlying mechanism of the photocatalytic system. Additionally, it delves into the latest techniques to enhance performance, including nanostructure design, elemental doping, and heterojunction construction. The applications of g-C3N4 based photocatalysts in hydrogen production are surveyed, underscoring the significance of catalyst active sites and g-C3N4 synthesis pathways. At length, concluded are insights into the challenges and opportunities presented by g-C3N4 based photocatalysts for achieving heightened hydrogen production. [ABSTRACT FROM AUTHOR]

Two thermoplastic polyurethanes (TPUs) based on the same monomers and composition were produced by two different production methods - hand mix batch process and continuous band casting. The soft segment was poly(hydrofuran) (PTHF) with a molar mass of 1000 and the hard segment was made of 1,4-butanediol (BD) and 4,40-methylene diphenyl diisocyanate (MDI). The hard segment content amounted to 42%. The distinctions in crystallization and thermal behavior and mechanical properties of the two TPUs were ascribed to differences in the hard and soft block length distribution caused by the different production methods. Using thermal fractionation - a series of successive self-nucleation and annealing steps - the minor differences in hard block length distribution could be shown and quantified. The length distribution of the hard and soft blocks of the machine-produced sample was narrower than that of the hand-cast sample. The former with the narrow block distribution showed thicker and mechanically and thermally more stable hard domains. The more uniform block length distribution facilitated crystallization and resulted in improved tensile recovery behavior and elasticity. The second with the broader distribution, however, showed the highest tensile strength at break, which was ascribed to an improved strain-induced hardening of the soft phase. [ABSTRACT FROM AUTHOR]

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Objective: The aim of this study was to compare the pharmacokinetics and steady-state serum concentrations of lenvatinib in adult and juvenile rats. Experimental study: An ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method was developed to quantify lenvatinib in the serum and liver of rats. Six juvenile and six adult rats in each group were orally administered with a single dose of 7.0 mg/kg lenvatinib suspension for pharmacokinetics. Another 12 juvenile and adult rats were subjected to oral gavage with 7.0 mg/kg lenvatinib once daily for 5 days. Biofluild samples were pre-treated by protein precipitation and sorafenib was used as the internal standard for UPLC-MS analysis. The pharmacokinetic parameters were estimated by compartment and statistical model. The mRNA expression of CYP3A2 and SLC22A1 in liver of adult and juvenile rats was measured by real-time fluorescence quantitative PCR (RT-qPCR). Results: The UPLC-MS method met the requirements for quantitative analysis of lenvatinib in serum and liver. The pharmacokinetic results showed that the mean retention time (MRT(0-∞)) was 19.64 ± 7.64 h and 126.38 ± 130.18 h, with AUC(0-∞) values of 3.97 ± 0.73 μg·mL-1 h and 5.95 ± 2.27 μg mL-1 h in adult and juvenile rats, respectively. When comparing adult rats (0.35 ± 0.15 μg/mL) to juvenile rats, no significant differences were observed in steady-state serum lenvatinib (0.32 ± 0.11 μg/ mL), but a noteworthy decrease to one-third of steady-state liver lenvatinib was observed after multiple oral doses of lenvatinib in juvenile rats. Additional findings revealed that the mRNA expression of CYP3A2 and SLC22A1 was notably increased by 6.86 and 14.67 times, respectively, in juvenile rats compared to adult rats. Conclusion: Juvenile rats exhibit lower levels of lenvatinib in the liver’s steadystate, potentially due to the disparity in CYP3A2 mRNA expression. These results imply that the dosage of lenvatinib for pediatric patients may need to be augmented in order to attain the desired clinical outcome [ABSTRACT FROM AUTHOR]

As a leading contributor to coronary artery disease (CAD) and stroke, atherosclerosis has become one of the major cardiovascular diseases (CVD) negatively impacting patients worldwide. The endothelial injury is considered to be the initial step of the development of atherosclerosis, resulting in immune cell migration and activation as well as inflammatory factor secretion, which further leads to acute and chronic inflammation. In addition, the inflammation and lipid accumulation at the lesions stimulate specific responses from different types of cells, contributing to the pathological progression of atherosclerosis. As a result, recent studies have focused on using molecular biological approaches such as gene editing and nanotechnology to mediate cellular response during atherosclerotic development for therapeutic purposes. In this review, we systematically discuss inflammatory pathogenesis during the development of atherosclerosis from a cellular level with a focus on the blood cells, including all types of immune cells, together with crucial cells within the blood vessel, such as smooth muscle cells and endothelial cells. In addition, the latest progression of molecular-cellular based therapy for atherosclerosis is also discussed. We hope this review article could be beneficial for the clinical management of atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Children with influenza B virus infection have a higher susceptibility and higher severity of illness. The activation and disorder of immune function play an important role in the severity of influenza virus infection. This study aims to investigate whether early lymphocyte count and cytokines can provide predictive value for the progression in children with influenza B virus pneumonia. Methods: A retrospective cohort study was conducted to analyze the clinical data of children with influenza B virus pneumonia from December 1, 2021, to March 31, 2022, in the National Children’s Regional Medical Center (Shengjing Hospital of China Medical University). According to the severity of the disease, the children were divided into a mild group and a severe group, and the clinical characteristics, routine laboratory examination, lymphocyte subsets, and cytokines were compared. Results: A total of 93 children with influenza B virus pneumonia were enrolled, including 70 cases in the mild group and 23 cases in the severe group. Univariate analysis showed that drowsiness, dyspnea, white blood cell (WBC), lymphocytes, monocytes, procalcitonin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), fibrinogen (FIB), Immunoglobulin M (IgM), lung consolidation, total T cell count, CD4+ T cell count, CD8+ T cell count, NK cell count, NK cell % and B cell % had statistical differences between the mild and severe groups (P<0.05). In multivariate logistic regression analysis, reduced ALT (OR = 1.016), FIB (OR = 0.233), CD8+ T cell count (OR = 0.993) and NK cell count (OR = 0.987) were independently associated with the development of severe influenza B virus pneumonia. Conclusions: The levels of T lymphocytes and NK cells were related to the progression of influenza B virus pneumonia in children, and the reduction of CD8+ T cell count and NK cell count can be used as independent risk factors for predicting the severity of influenza B virus pneumonia. [ABSTRACT FROM AUTHOR]

The unique cancer-associated immunosuppression in brain, combined with a paucity of infiltrating T cells, contributes to the low response rate and poor treatment outcomes of T cell-based immunotherapy for patients diagnosed with glioblastoma multiforme (GBM). Here, we report on a self-assembling paclitaxel (PTX) filament (PF) hydrogel that stimulates macrophage-mediated immune response for local treatment of recurrent glioblastoma. Our results suggest that aqueous PF solutions containing aCD47 can be directly deposited into the tumor resection cavity, enabling seamless hydrogel filling of the cavity and long-term release of both therapeutics. The PTX PFs elicit an immune-stimulating tumor microenvironment (TME) and thus sensitizes tumor to the aCD47-mediated blockade of the antiphagocytic "don't eat me" signal, which subsequently promotes tumor cell phagocytosis by macrophages and also triggers an antitumor T cell response. As adjuvant therapy after surgery, this aCD47/PF supramolecular hydrogel effectively suppresses primary brain tumor recurrence and prolongs overall survivals with minimal off-target side effects. [ABSTRACT FROM AUTHOR]

Introduction: Glioblastoma is a malignant brain tumor with poor prognosis. Lactate is the main product of tumor cells, and its secretion may relate to immunocytes’ activation. However, its role in glioblastoma is poorly understood. Methods: This work performed bulk RNA-seq analysis and single cell RNA-seq analysis to explore the role of lactate in glioblastoma progression. Over 1400 glioblastoma samples were grouped into different clusters according to their expression and the results were validated with our own data, the xiangya cohort. Immunocytes infiltration analysis, immunogram and the map of immune checkpoint genes’ expression were applied to analyze the potential connection between the lactate level with tumor immune microenvironment. Furthermore, machine learning algorithms and cell-cell interaction algorithm were introduced to reveal the connection of tumor cells with immunocytes. By co-culturing CD8 T cells with tumor cells, and performing immunohistochemistry on Xiangya cohort samples further validated results from previous analysis. Discussion: In this work, lactate is proved that contributes to glioblastoma immune suppressive microenvironment. High level of lactate in tumor microenvironment can affect CD8 T cells’ migration and infiltration ratio in glioblastoma. To step further, potential compounds that targets to samples from different groups were also predicted for future exploration. [ABSTRACT FROM AUTHOR]

Background: Pioglitazone is considered a potential therapy for non-alcoholic fatty liver disease (NAFLD). However, different effects of pioglitazone on NAFLD have been demonstrated in diabetic and non-diabetic patients. Herein, a metaanalysis of randomized, placebo-controlled trials was carried out to indirectly compare pioglitazone in NAFLD patients with vs. without type 2 diabetes. Methods: Randomized controlled trials (RCTs) of pioglitazone vs. placebo involving NAFLD patients with or without type 2 diabetes/prediabetes collected from databases were enrolled into this analysis. Methodological quality was employed to evaluate the domains recommended by the Cochrane Collaboration. The analysis covered the changes in histology (fibrosis, hepatocellular ballooning, inflammation, steatosis), liver enzymes, blood lipids, fasting blood glucose (FBS), homeostasis model assessment-IR (HOMA-IR), weight and body mass index (BMI) before and after treatment, and adverse events. Results: The review covered seven articles, with 614 patients in total, of which three were non-diabetic RCTs. No difference was found in patients with vs. without type 2 diabetes in histology, liver enzymes, blood lipids, HOMA-IR, weight, BMI, and FBS. Moreover, no significant difference was revealed in adverse effects between NAFLD patients with diabetes and without DM, except the incidence of edema that was found to be higher in the pioglitazone group than in the placebo group in NAFLD patients with diabetes. Conclusions: Pioglitazone could exert a certain effect on alleviating NAFLD, which was consistent between non-diabetic NAFLD patients and diabetic NAFLD patients in improving histopathology, liver enzymes, and HOMA-IR and reducing blood lipids. Furthermore, there were no adverse effects, except the incidence of edema which is higher in the pioglitazone group in NAFLD patients with diabetes. However, large sample sizes and well-designed RCTs are required to further confirm these conclusions. [ABSTRACT FROM AUTHOR]

Background: Respiratory diseases are common and frequent diseases. Due to the high pathogenicity and side effects of respiratory diseases, the discovery of new strategies for drug treatment is a hot area of research. Scutellaria baicalensis Georgi (SBG) has been used as a medicinal herb in China for over 2000 years. Baicalin (BA) is a flavonoid active ingredient extracted from SBG that BA has been found to exert various pharmacological effects against respiratory diseases. However, there is no comprehensive review of the mechanism of the effects of BA in treating respiratory diseases. This review aims to summarize the current pharmacokinetics of BA, baicalin-loaded nano-delivery system, and its molecular mechanisms and therapeutical effects for treating respiratory diseases. Method: This review reviewed databases such as PubMed, NCBI, and Web of Science from their inception to 13 December 2022, in which literature was related to "baicalin", "Scutellaria baicalensis Georgi", "COVID-19", "acute lung injury", "pulmonary arterial hypertension", "asthma", "chronic obstructive pulmonary disease", "pulmonary fibrosis", "lung cancer", "pharmacokinetics", "liposomes", "nano-emulsions", "micelles", "phospholipid complexes", "solid dispersions", "inclusion complexes", and other terms. Result: The pharmacokinetics of BA involves mainly gastrointestinal hydrolysis, the enteroglycoside cycle, multiple metabolic pathways, and excretion in bile and urine. Due to the poor bioavailability and solubility of BA, liposomes, nanoemulsions, micelles, phospholipid complexes, solid dispersions, and inclusion complexes of BA have been developed to improve its bioavailability, lung targeting, and solubility. BA exerts potent effects mainly by mediating upstream oxidative stress, inflammation, apoptosis, and immune response pathways. It regulates are the NF-κB, PI3K/AKT, TGF-β/Smad, Nrf2/HO-1, and ERK/GSK3β pathways. Conclusion: This review presents comprehensive information on BA about pharmacokinetics, baicalin-loaded nano-delivery system, and its therapeutic effects and potential pharmacological mechanisms in respiratory diseases. The available studies suggest that BA has excellent possible treatment of respiratory diseases and is worthy of further investigation and development. [ABSTRACT FROM AUTHOR]

Objectives: Post-stroke depression (PSD) is a common and serious psychiatric complication which hinders functional recovery and social participation of stroke patients. Stroke is characterized by dynamic changes in metabolism and hemodynamics, however, there is still a lack of metabolism-associated effective and reliable diagnostic markers and therapeutic targets for PSD. Our study was dedicated to the discovery of metabolism related diagnostic and therapeutic biomarkers for PSD. Methods: Expression profiles of GSE140275, GSE122709, and GSE180470 were obtained from GEO database. Differentially expressed genes (DEGs) were detected in GSE140275 and GSE122709. Functional enrichment analysis was performed for DEGs in GSE140275. Weighted gene co-expression network analysis (WGCNA) was constructed in GSE122709 to identify key module genes. Moreover, correlation analysis was performed to obtain metabolism related genes. Interaction analysis of key module genes, metabolism related genes, and DEGs in GSE122709 was performed to obtain candidate hub genes. Two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) and random forest, were used to identify signature genes. Expression of signature genes was validated in GSE140275, GSE122709, and GSE180470. Gene set enrichment analysis (GSEA) was applied on signature genes. Based on signature genes, a nomogram model was constructed in our PSD cohort (27 PSD patients vs. 54 controls). ROC curves were performed for the estimation of its diagnostic value. Finally, correlation analysis between expression of signature genes and several clinical traits was performed. Results: Functional enrichment analysis indicated that DEGs in GSE140275 enriched in metabolism pathway. A total of 8,188 metabolism associated genes were identified by correlation analysis. WGCNA analysis was constructed to obtain 3,471 key module genes. A total of 557 candidate hub genes were identified by interaction analysis. Furthermore, two signature genes (SDHD and FERMT3) were selected using LASSO and random forest analysis. GSEA analysis found that two signature genes had major roles in depression. Subsequently, PSD cohort was collected for constructing a PSD diagnosis. Nomogram model showed good reliability and validity. AUC values of receiver operating characteristic (ROC) curve of SDHD and FERMT3 were 0.896 and 0.964. ROC curves showed that two signature genes played a significant role in diagnosis of PSD. Correlation analysis found that SDHD (r = 0.653, P < 0.001) and FERM3 (r = 0.728, P < 0.001) were positively related to the Hamilton Depression Rating Scale 17-item (HAMD) score. Conclusion: A total of 557 metabolism associated candidate hub genes were obtained by interaction with DEGs in GSE122709, key modules genes, and metabolism related genes. Based on machine learning algorithms, two signature genes (SDHD and FERMT3) were identified, they were proved to be valuable therapeutic and diagnostic biomarkers for PSD. Early diagnosis and prevention of PSD were made possible by our findings. [ABSTRACT FROM AUTHOR]

Background: Juvenile polyposis syndrome (JPS) is a rare autosomal dominant disorder that is a type of hamartomatous polyp syndrome, and its incidence rate is approximately 1/100000. The main clinical feature is the presence of multiple juvenile polyps in the gastrointestinal tract, most often in the colorectal tract. We present a case of juvenile polyposis syndrome with massive gastric polyposis. Case presentation: A 50-year-old male was admitted to the hospital due to abdominal distension and poor appetite. Gastroscopy revealed a large number of gastric polyps. Pathological findings revealed gastric juvenile polyps. Genetic testing revealed that he and his brother both carried SMAD4: c.266_269del germline pathogenic variant. The final diagnosis was juvenile polyposis syndrome of the stomach. He once suffered from colon cancer and bladder cancer. One of his brothers died of colon cancer, and the other brother suffered from colon polyps. Conclusions: Gastric involvement in juvenile polyposis syndrome is relatively rare. When massive gastric polyposis is found, gene detection should be carried out as soon as possible, so that rapid diagnosis and treatment can be obtained. [ABSTRACT FROM AUTHOR]

Objective: Scholars have conducted in‐depth research on social change agents, but there are few collaborative studies in this realm between sociology and psychology. From the perspective of psychobiography, this before study uses Jung's Analytical Psychology as a theoretical framework to explore Jack Ma's influence on business change, thereby revealing the deep motivation behind Jack Ma's sudden retirement and choice to be a teacher. Method: This study has collected primary and secondary data about Jack Ma. QSR Nvivo 11.0 was used to encode the text based on video transcription, and then the data were analyzed. This study refers to the key factors of growth and follows the primary indicators of psychological saliency to sort out the data and find out what has special psychological significance, and then conducts three coding processes. Results: This study found that the teacher complex and the martial arts complex are the breakthrough points to understand the business innovator Jack Ma. Conclusion: Jack Ma shapes the image of ordinary teachers through his image management strategy, conceals his deep internal martial arts complex, and balances the displayed martial arts personality mask. He has achieved great success in business innovator, while drawing on his internal personality conflicts to his advantage. [ABSTRACT FROM AUTHOR]

Background: Glioma is one of the most common, primary, and lethal adult brain tumors because of its extreme aggressiveness and poor prognosis. Several recent studies relevant to the immune function of CD44, a transmembrane glycoprotein as a significant hyaluronic acid receptor, have achieved great success, revealing the critical role of CD44 in immune infiltration in gliomas. The overexpression of CD44 has been verified to correlate with cancer aggressiveness and migration, while the clinical and immune features of CD44 expression have not yet been thoroughly characterized in gliomas. Methods: Molecular and clinical data of glioma collected from publicly available genomic databases were analyzed. Results: CD44 was up-expressed in malignant gliomas, notably in the 1p/19q non-codeletion cases, isocitrate dehydrogenase (IDH) wild-type, and mesenchymal subtypes in GBM samples. CD44 expression level strongly correlates with stromal and immune cells, mainly infiltrating the glioma microenvironment by single-cell sequencing analysis. Meanwhile, CD44 can be a promising biomarker in predicting immunotherapy responses and mediating the expression of PD-L1. Finally, RUNX1/CD44 axis could promote the proliferation and migration of gliomas. Conclusions: Therefore, CD44 was responsible for glioma growth and progression. It could potentially lead to a novel target for glioma immunotherapy or a prognostic biomarker. [ABSTRACT FROM AUTHOR]

Background: The incidence and mortality of uterine corpus endometrial carcinoma (UCEC) are increasing yearly. There is currently no screening test for UCEC, and progress in its treatment is limited. It is important to identify new biomarkers for screening, diagnosing and predicting the outcomes of UCEC. A large number of previous studies have proven that KNL1 is crucial in the development of lung cancer, colorectal cancer and cervical cancer, but there is a lack of studies about the role of KNL1 in the development of UCEC. Methods: The mRNA and protein expression data of KNL1 in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and UALCAN databases and related clinical data were used to analyze the expression differences and clinical correlations of KNL1 in UCEC. A total of 108 clinical samples were collected, and the results of bioinformatics analysis were verified by immunohistochemistry. KNL1 and its related differentially expressed genes were used to draw a volcano map, construct a PPI protein interaction network, and perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA) and immune infiltration analysis to predict the function of KNL1 during UCEC progression. The prognostic data of TCGA and 108 clinical patients were used to analyze the correlation of KNL1 expression with the survival of patients, and KM survival curves were drawn. The UCEC cell lines Ishikawa and Hec-1-A were used to verify the function of KNL1. Results: KNL1 is significantly overexpressed in UCEC and is associated with a poor prognosis. KNL1 overexpression is closely related to cell mitosis, the cell cycle and other functions and is correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade and other characteristics of UCEC patients. Knockdown of KNL1 expression in UCEC cell lines can inhibit their proliferation, invasion, metastasis and other phenotypes. Conclusion: KNL1 is a prognostic and diagnostic biomarker associated with immune evasion in patients with UCEC. [ABSTRACT FROM AUTHOR]

Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovering new anti-tumour drugs to improve tumour targeting effects and reduce off-target toxicities. Colchicine is one of the most prominent and historically microtubule-targeting drugs, but its clinical applications are hindered by notorious adverse effects. In this study, we presented a novel tumour-specific conjugate 9 that consists of deacetylcolchicine (Deac), biotin, and a cleavable disulphide linker. 9 was found to exhibit potent anti-tumour activity and exerted higher selectivity between tumour and nontarget cells than Deac. The targeting moiety biotin might enhance the transport capability and selectivity of 9 to tumour cells via biotin receptor-mediated endocytosis. The tubulin polymerisation activity of 9 (with DTT) was close to the parent drug Deac. These preliminary results suggested that 9 is a high potency and reduced toxicity antitumor agent and worthy of further investigation. [ABSTRACT FROM AUTHOR]

Gliomas, originating from the glial cells, are the most lethal type of primary tumors in the central nervous system. Standard treatments like surgery have not significantly improved the prognosis of glioblastoma patients. Recently, immune therapy has become a novel and effective option. As a conserved group of transcriptional regulators, the Sry-type HMG box (SOX) family has been proved to have a correlation with numerous diseases. Based on the large-scale machine learning, we found that the SOX family, with significant immune characteristics and genomic profiles, can be divided into two distinct clusters in gliomas, among which SOX10 was identified as an excellent immune regulator of macrophage in gliomas. The high expression of SOX10 is related to a shorter OS in LGG, HGG, and pan-cancer groups but benefited from the immunotherapy. It turned out in single-cell sequencing that SOX10 is high in neurons, M1 macrophages, and neural stem cells. Also, macrophages are found to be elevated in the SOX10 high-expression group. SOX10 has a positive correlation with macrophage cytokine production and negative regulation of macrophages’ chemotaxis and migration. In conclusion, our study demonstrates the outstanding cluster ability of the SOX family, indicating that SOX10 is an immune regulator of macrophage in gliomas, which can be an effective target for glioma immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Tracheostomy is a lifesaving procedure provided for patients with severe neurological injury. However, there is a lack of clarity about whether patients can be decannulated within 6months in those receiving tracheostomy and what factors can be detected as a predictor for decannulation. Objective: The objective of this study was to explore predictive factors of decannulation in patients with neurological injury receiving tracheostomy within 6 months and construct a novel nomogram model for clinical diagnosis and treatment. Methods: This retrospective observational study enrolled patients with neurological injury who were admitted to the ICU of neurosurgical department in the First Affiliated Hospital of Nanjing Medical University between January 2016 and March 2021. Patients were divided into decannulation group and cannulation group according to whether tracheostomy tube removal was performed within 6 months after tracheostomy. Multivariable logistic regression analysis was performed to determine associated risk factors with a bootstrap backward selection process. The nomogram to assess the probability of decannulation at 6 months was constructed based on the regression coefficients of the associated factors and validated by bootstrap resampling. Model performance was measured by examining discrimination (Harrell's C-index), calibration (calibration plots), and utility (Kaplan--Meier curves stratified by the tertile of the predicted probability calculated and subgroup analysis stratified by age and intervention). Results: A total of 40.1% (147/367) of patients decannulated within 6 months. Significant variables in multivariable logistic regression analysis were age (odds ratio [OR], 0.972; 95% confidence interval [CI], 0.954-0.990), National Institutes of Health Stroke Scale (NIHSS) score (OR, 0.936; 95% CI, 0.911-0.963), early rehabilitation (OR, 5.062; 95% CI, 2.889--8.868), shock (OR, 0.175; 95% CI, 0.058-0.533), and secondary surgery (OR, 0.210; 95% CI, 0.078--0.566). The area under receiver operating characteristic curve estimated with these variables was of 0.793 (95% CI, 0.747-0.838; P < 0.001). A nomogram prediction model was constructed to predict the probability of decannulation in tracheostomized patients with a concordance index of 0.788 after internal validation. Conclusion: We developed a nomogram that can predict the probability of decannulation within 6 months in tracheostomized neurological injury patients. The nomogram, including age, NIHSS scores, early rehabilitation, shock, and secondary surgery, may assist clinicians in estimating patients' prognosis. [ABSTRACT FROM AUTHOR]

Immunogenic cell death (ICD) is a form of cell death that leads to the regulation and activation of the immune response, which is characterized by the exposure and release of damage‐associated molecular patterns (DAMPs) in the tumor microenvironment. Accumulating evidence has revealed the significance of ICD-related genes in tumor progression and therapeutic response. In this study, we obtained two ICD-related clusters for glioblastoma (GBM) by applying consensus clustering, and further constructed a risk signature on account of the prognostic ICD genes. Based on the risk signature, we found that higher risk scores were associated with worse patient prognosis. Besides, the results illustrated that ferroptosis regulators/markers were highly enriched the high-risk group, and ferroptosis were correlated with cytokine signaling pathway and other immune-related pathways. We also discovered that highrisk scores were correlated to specific immune infiltration patterns and good response to immune checkpoint blockade (ICB) treatment. In conclusion, our study highlights the significance of ICD-related genes as prognostic biomarkers and immune response indicators in GBM. And the risk signature integrating prognostic genes possessed significant potential value to predict the prognosis of patients and the efficacy of ICB treatment. [ABSTRACT FROM AUTHOR]

Background: Single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) is one of the most effective bariatric procedures in the treatment of type 2 diabetes mellitus (T2DM). However, the mechanisms by which SADI-S improves T2DM are not well-known. Objective: To explore the effects of SADI-S on metabolites in the stool of rats with T2DM. Methods: Twenty rats were fed on high-fat diet and administered with a lowdose (30mg/kg) of streptozotocin to establish T2DM models. The rats were then randomly assigned to the SADI-S group (n=10) and sham operation group (n=9). Stool samples were collected from all rats at 8 weeks after surgery and stored at -80 ℃. Metabolomics analysis was performed to identify differential metabolites through ultra-performance liquid chromatography-mass spectrometry. Results: At 8-week after surgery, rats of the SADI-S group showed significantly decreased fasting blood glucose, glucose tolerance test 2-hour, glycated haemoglobin, and body weight compared with those of the sham group. A total of 245 differential metabolites were identified between the two groups. Among them, 16 metabolites such as branched-chain amino acids (valine), aromatic amino acid (phenylalanine), bile acid (cholic acid, lithocholic acid, and β-muricholic acid), short-chain fatty acid (isobutyric acid), and phospholipid [lysoPE(17:0), lysoPE(20:3) and lysoPS(16:0)] were associated to the T2DM remission after SADI-S. Conclusion: SADI-S improves T2DM in rats by regulating phenylalanine biosynthesis, valine, phenylalanine, alanine, glutamate, proline, bile acid, and phospholipid metabolism pathways. [ABSTRACT FROM AUTHOR]

Ischemic and hemorrhagic stroke (including intracerebral hemorrhage, intraventricular hemorrhage, and subarachnoid hemorrhage) is the dominating cause of disability and death worldwide. Neuroinflammation, blood-brain barrier (BBB) disruption, neuronal death are the main pathological progress, which eventually causes brain injury. Increasing evidence indicated that lipocalin 2 (LCN2), a 25k-Da acute phase protein from the lipocalin superfamily, significantly increased immediately after the stroke and played a vital role in these events. Meanwhile, there exists a close relationship between LCN2 levels and the worse clinical outcome of patients with stroke. Further research revealed that LCN2 elimination is associated with reduced immune infiltrates, infarct volume, brain edema, BBB leakage, neuronal death, and neurological deficits. However, some studies revealed that LCN2 might also act as a beneficial factor in ischemic stroke. Nevertheless, the specific mechanism of LCN2 and its primary receptors (24p3R and megalin) involving in brain injury remains unclear. Therefore, it is necessary to investigate the mechanism of LCN2 induced brain damage after stroke. This review focuses on the role of LCN2 and its receptors in brain injury and aiming to find out possible therapeutic targets to reduce brain damage following stroke. [ABSTRACT FROM AUTHOR]

Accumulating evidence has demonstrated that the immune cells have an emerging role in controlling anti-tumor immune responses and tumor progression. The comprehensive role of mast cell in glioma has not been illustrated yet. In this study, 1,991 diffuse glioma samples were collected from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). xCell algorithm was employed to define the mast cell-related genes. Based on mast cell-related genes, gliomas were divided into two clusters with distinct clinical and immunological characteristics. The survival probability of cluster 1 was significantly lower than that of cluster 2 in the TCGA dataset, three CGGA datasets, and the Xiangya cohort. Meanwhile, the hypoxic and metabolic pathways were active in cluster 1, which were beneficial to the proliferation of tumor cells. A potent prognostic model based on mast cell was constructed. Via machine learning, DRG2 was screened out as a characteristic gene, which was demonstrated to predict treatment response and predict survival outcome in the Xiangya cohort. In conclusion, mast cells could be used as a potential effective prognostic factor for gliomas. [ABSTRACT FROM AUTHOR]

Adversarial examples pose many security threats to convolutional neural networks (CNNs). Most defense algorithms prevent these threats by finding differences between the original images and adversarial examples. However, the found differences do not contain features about the classes, so these defense algorithms can only detect adversarial examples without recovering the correct labels. In this regard, we propose the Adversarial Feature Genome (AFG), a novel type of data that contain both the differences and features about classes. This method is inspired by an observed phenomenon, namely, the Adversarial Feature Separability, where the difference between the feature maps of the original images and adversarial examples becomes larger with deeper layers. On top of that, we further develop an adversarial example recognition framework that detects adversarial examples and can recover the correct labels. In the experiments, the detection and classification of adversarial examples by AFGs has an accuracy of more than 90.01% in various attack scenarios. To the best of our knowledge, our method is the first method that focuses on both attack detecting and recovering. AFG gives a new data-driven perspective to improve the robustness of CNNs. [ABSTRACT FROM AUTHOR]

Species within the Aspergillus spp. cause a wide range of infections in humans, including invasive pulmonary aspergillosis, chronic pulmonary aspergillosis, and allergic bronchopulmonary aspergillosis, and are associated with high mortality rates. The incidence of pulmonary aspergillosis (PA) is on the rise, and the emergence of triazole-resistant Aspergillus spp. isolates, especially Aspergillus fumigatus, limits the efficacy of mold-active triazoles. Therefore, host-directed and novel adjunctive therapies are required to more effectively combat PA. In this review, we focus on PA from a microbiome perspective. We provide a general overview of the effects of the lung and gut microbiomes on the growth of Aspergillus spp. and host immunity. We highlight the potential of the microbiome as a therapeutic target for PA. [ABSTRACT FROM AUTHOR]

The aberrant protein disulfide isomerase A5 (PDIA5) expression was relevant to the poor prognosis of patients with human cancers. However, its relationship with the epigenetic and genetic alterations and its effect on tumor immunity is still lacking. In the present study, we comprehensively analyzed the immune infiltration role of PDIA5 in human cancers based on large-scale bioinformatics analyses and in vitro experiments. Obvious DNA methylation and moderate alteration frequency of PDIA5 were observed in human cancers. The expression level of PDIA5 was significantly correlated with infiltrated immune cells, immune pathways, and other immune signatures. We found that cancer cells and macrophages exhibited high PDIA5 expression in human cancers using the single-cell RNA sequencing analysis. We also demonstrated the interaction between PDIA5 and immune cells in glioblastoma multiforme (GBM). Multiplex immunofluorescence staining showed the upregulated expression level of PDIA5 and the increased number of M2 macrophage markers-CD163 positive cells in pan-cancer samples. Notably, PDIA5 silencing resulted in upregulated expression of PD-L1 and SPP1 in U251 cells. Silencing of PDIA5 in hepG2 cells, U251 cells, and PC3 cells contributed to a decline in their ability of proliferation, clone formation, and invasion and inhibited the migration of cocultured M2 macrophages. Additionally, PDIA5 also displayed predictive value in the immunotherapy response of both murine and human cancer cohorts. Overall, our findings indicated that PDIA5 might be a potential target for immunotherapies in cancers. [ABSTRACT FROM AUTHOR]

Glioma is the most malignant cancer of the central nervous system. There are various therapies for treating gliomas, but their outcomes are not satisfactory. Therefore, new targets for glioma treatment are needed. This study examined the cadherin-6 (CDH6) expression in gliomas using The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets. CDH6 expression positively correlated with the World Health Organization (WHO) tumor grade and negatively correlated with patient prognosis. A significant decrease in CDH6 promoter methylation was identified with an increase in the WHO grade severity. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that CDH6 might be involved in cell-cell interactions and immune processes in the glioma microenvironment. Weighted gene co-expression network analysis revealed a correlation between CDH6 and cell adhesion molecules, focal adhesions, phosphatidylinositol 3-kinase-protein kinase B signaling pathways, nuclear division, chromosome segregation, mitotic nuclear division, and immunerelated pathways. CDH6 strongly correlated with immunosuppressive cells, including regulatory T cells, monocytes, macrophages, tumor-associated macrophages, and myeloid-derived suppressor cells. It also showed correlations with immune-active cells such as B cells, CD8+ T cells, and dendritic cells. Single-cell analysis showed that CDH6 was expressed mainly in astrocyte (AC)-like malignant cells. Differentially expressed genes of AC-like malignant cells were found to be associated with stress response, membranous processes, viral infections, and several types of cancers. Potential drugs associated with high CDH6 expression were also predicted, including AMG-22, rutin, CCT128930, deforolimus, bis(maltolato)oxovanadium, anagrelide, vemurafenib, CHIR-98014, and AZD5582. Thus, this study showed that CDH6 correlates with glioma immune infiltration, it is expressed mainly in AC-like malignant cells, and it may act as a new target for glioma therapy. [ABSTRACT FROM AUTHOR]

Background: JMJD8 has recently been identified as a cancer-related gene, but current studies provide limited information. We aimed to clarify its roles and the potential mechanisms in pan-cancer. Methods: Pan-cancer bulk sequencing data and online web tools were applied to analyze JMJD8’s correlations with prognosis, genome instability, cancer stemness, DNA repair, and immune infiltration. Moreover, single-cell datasets, SpatialDB database, and multiple fluorescence staining were used to validate the association between JMJD8 expression and M2 macrophages. Further, we utilized ROCplotter and cMap web tool to analyze the therapeutic responses and screened JMJD8-targeted compounds, respectively, and we used AlphaFold2 and Discovery Studio to conduct JMJD8 homology modeling and molecular docking. Results: We first noticed that JMJD8 was an oncogene in many cancer types. High JMJD8 was associated with lower genome stability. We then found that high JMJD8 correlated with high expression of mismatch repair genes, stemness, homologous repair gene signature in more than 9 cancers. ESTIMATE and cytokine analyses results presented JMJD8’s association with immunosuppression. Also, immune checkpoint CD276 was positively relevant to JMJD8. Subsequently, we validated JMJD8 as the M2 macrophage marker and showed its connection with other immunosuppressive cells and CD8+ T-cell depression. Finally, potential JMJD8-targeted drugs were screened out and docked to JMJD8 protein. Conclusion: We found that JMJD8 was a novel oncogene, and it correlated with immunosuppression and DNA repair. JMJD8 was highly associated with immune checkpoint CD276 and was an M2 macrophage biomarker in many cancers. This study will reveal JMJD8’s roles in pan-cancer and its potential as a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Group A streptococcus (GAS, Streptococcus pyogenes) is a common pathogen that can cause a variety of human diseases. Streptolysin O (SLO) is an exotoxin produced by GAS. It is a pore-forming toxin (PFT) that exhibits high in vivo toxicity. SLO enables GAS to evade phagocytosis and clearance by neutrophils, induces eukaryotic cell lysis, and activates inflammatory bodies. Luteolin is a natural compound that is produced by a wide range of plant species, and recent studies have shown that luteolin can inhibit the growth and alter the morphological of GAS. Here, we reported that luteolin can weaken the cytotoxicity and hemolytic activity of SLO in vitro. Briefly, luteolin bound SLO with high affinity, inhibited its dissolution of erythrocytes, affected its conformational stability and inhibited the formation of oligomers. To further verify the protective effect of luteolin, we used an in vitro SLOinduced human laryngeal carcinoma epithelial type-2 cells (HEp-2) model. Notably, our results showed luteolin protected HEp-2 cells from SLO induced cytotoxicity and changed in cell membrane permeability. In addition, we explored the role of luteolin in protecting mice from GAS-mediated injury using an aerosolized lung delivery model, and our results indicate that luteolin increases murine survival rate following inoculation with a lethal dose of GAS, and that survival was also associated with decreased pathological damage to lung tissue. Our results suggest that luteolin may be a novel drug candidate for the treatment of GAS infection [ABSTRACT FROM AUTHOR]

Highly dispersed Ni-based catalysts were derived from self-reconstruction of the LaNiO3 perovskite, which were prepared via the sol-gel process. Activity measurements indicated that the as-prepared catalysts exhibit an excellent dry methane reforming catalytic performance, which can achieve CH4 conversion of 84.17% and 83.35% at 650 1C at a gas hourly space velocity (GHSV) of 128 L (gcat h)-1. The physicochemical characterization of the as-prepared catalysts suggested that the transition layer of La2NiO4 is formed between metallic Ni0 and the La(OH)3 support. The Ni0-Ni2+ dipole on the support is relevant to the catalytic activity for the dry methane reforming reaction. [ABSTRACT FROM AUTHOR]

Lorcaserin is a serotonergic agonist specific to the 5-hydroxytryptamine 2c receptor (5-HT2CR) that is FDA approved for the long-term management of obesity with or without at least one weight-related comorbidity. Lorcaserin can restrain patients’ appetite and improve insulin sensitivity and hyperinsulinemia mainly through activating 5-HT2CR in the hypothalamus. It is known that the mCPP, a kind of 5-HT2CR agonist, decreases plasma insulin concentration in mice and previous research in our laboratory found that mCPP inhibited glucose-stimulated insulin secretion (GSIS) by activating 5-HT2CR on the β cells. However, the effect of lorcaserin on GSIS of pancreatic β cell has not been studied so far. The present study found that 5-HT2CR was expressed in both mouse pancreatic β cells and β-cell–derived MIN6 cells. Dose-dependent activation of 5-HT2CR by lorcaserin suppressed GSIS and SB242084 or knockdown of 5-HT2CR abolished lorcaserin’s effect in vitro. Additionally, lorcaserin also suppressed GSIS in high-fat diet (HFD)-fed mice in dose-dependent manner. Lorcaserin did not change insulin synthesis ATP content, but lorcaserin decrease cytosolic free calcium level [(Ca2+)i] in MIN6 cells stimulated with glucose and also inhibit insulin secretion and (Ca2+)i in MIN6 treated with potassium chloride. Furthermore, stimulation with the L-type channel agonist, Bay K8644 did not restore GSIS in MIN6 exposed to lorcaserin. Lorcaserin inhibits the cAMP generation of MIN6 cells and pretreatment with the Gα i/o inhibitor pertussis toxin (PTX), abolished lorcaserin-induced suppression of GSIS in β cells, while membrane-permeable cAMP analogue db-cAMP had same effect as PTX. These date indicated lorcaserin coupled to PTX-sensitive Gα i/o proteins in β cells reduced intracellular cAMP level and Ca2+ influx, thereby causing GSIS dysfunction of β cell. These results highlight a novel signaling mechanism of lorcaserin and provide valuable insights into the further investigation of 5-HT2CR functions in β-cell biology and it also provides guidance for the clinical application of lorcaserin. [ABSTRACT FROM AUTHOR]