A robot-assisted tracheal intubation system based on a soft actuator?

PURPOSE: Tracheal intubation is the gold standard of airway protection and constitutes a pivotal life-saving technique frequently employed in emergency medical interventions. Hence, in this paper, a system is designed to execute tracheal intubation tasks automatically, offering a safer and more efficient solution, thereby alleviating the burden on physicians. METHODS: The system comprises a tracheal tube with a bendable front end, a drive system, and a tip endoscope. The soft actuator provides two degrees of freedom for precise orientation. It is fabricated with varying-hardness silicone and reinforced with fibers and spiral steel wire for flexibility and safety. The hydraulic actuation system and tube feeding mechanism enable controlled bending and delivery. Object detection of key anatomical features guides the robotic arm and soft actuator. The control strategy involves visual servo control for coordinated robotic arm and soft actuator movements, ensuring accurate and safe tracheal intubation. RESULTS: The kinematics of the soft actuator were established using a constant curvature model, allowing simulation of its workspace. Through experiments, the actuator is capable of 90° bending as well as 20° deflection on the left and right sides. The maximum insertion force of the tube is 2 N. Autonomous tracheal intubation experiments on a training manikin were successful in all 10 trials, with an average insertion time of 45.6 s. CONCLUSION: Experimental validation on the manikin demonstrated that the robot tracheal intubation system based on a soft actuator was able to perform safe, stable, and automated tracheal intubation. In summary, this paper proposed a safe and automated robot-assisted tracheal intubation system based on a soft actuator, showing considerable potential for clinical applications.

Interactions of different polyphenols with wheat germ albumin and globulin: Alterations in the conformation and emulsification properties of proteins.

In this study, chlorogenic acid (CA), piceatannol (PIC), epigallocatechin-3-gallate (EGCG) and ferulic acid (FA) was selected to explore the influence of polyphenol on the structural properties of wheat germ albumin (WGA) and wheat germ globulin (WGG). The emulsifying properties of the emulsions prepared by WGA-EGCG complex were also evaluated. The results indicated that all polyphenols could significantly enhance the antioxidant capacity of WGA and WGG. In particular, EGCG increased the ratio of random coil in WGA and WGG, resulting in protein unfolding and shifting from an order to disorder structure. In addition, lipid oxidation and protein oxidation of the soybean oil emulsion was significantly slowed down by WGA-EGCG. The stability of the emulsions under various environmental stress and the storage time was significantly improved by WGA-EGCG. These findings can provide a reference for expanding the application of wheat germ protein in food industry.

Role of BP-ANN in simulating greenhouse gas emissions from global aquatic ecosystems via carbon component-environmental factor coupling.

Inland waters (IW), estuarine areas (EA), and offshore areas (OA) function as aquatic systems in which the transport of carbon components results in the release of greenhouse gases (GHGs). Interconnected subsystems exhibit a greater greenhouse effect than individual systems. Despite this, there is a lack of research on how carbon loading and its components impact GHG emissions in various aquatic systems. In this study, we analyzed 430 aquatic sites to explore trade-off mechanisms among dissolved organic carbon (DOC), particulate organic carbon, dissolved inorganic carbon (DIC), and GHGs. The results revealed that IW emerged as the most significant GHG source, possessing a comprehensive global warming potential (GWP) of 0.78 ± 0.08 (10-2 Pg CO2-ep ha-1 year-1) for combined carbon dioxide, methane, and nitrous oxide. This surpassed the cumulative potentials of EA and OA (0.35 ± 0.05 (10-2 Pg CO2-ep ha-1 year-1)). Additionally, structural equation modeling indicated that GHG emissions resulted from a combination of carbon component loading and environmental factors. DOC exhibited a positive correlation with GWPs when influenced by biodegradable DOC. Total alkalinity and pH influenced DIC, leading to elevated pCO2 in aquatic systems, thereby enhancing GWPs. Predictive modeling using backpropagation artificial neural networks (BP-ANN) for GWPs, incorporating carbon components and environmental factors, demonstrated a good fit (R2 = 0.6078, RMSEaverage = 0.069, p > 0.05) between observed and predicted values. Enhancing the estimation of aquatic region feedback to GHG changes was achieved by incorporating corresponding water quality parameters. In summary, this study underscores the pivotal role of carbon components and environmental factors in aquatic regions for GHG emissions. The application of BP-ANN to estimate greenhouse effects from aquatic regions is highlighted, providing theoretical and experimental support for future advancements in monitoring and developing policies concerning the influence of water quality on GHG emissions.

Identification of Dihydrobenzofuran Neolignans as Novel PDE4 Inhibitors and Evaluation of Antiatopic Dermatitis Efficacy in DNCB-Induced Mice Model.

Atopic dermatitis is a chronic relapsing skin disease characterized by recurrent, pruritic, localized eczema, while PDE4 inhibitors have been reported to be effective as antiatopic dermatitis agents. 3',4-O-dimethylcedrusin (DCN) is a natural dihydrobenzofuran neolignan isolated from Magnolia biondii with moderate potency against PDE4 (IC50 = 3.26 ± 0.28 µM) and a binding mode similar to that of apremilast, an approved PDE4 inhibitor for the treatment of psoriasis. The structure-based optimization of DCN led to the identification of 7b-1 that showed high inhibitory potency on PDE4 (IC50 = 0.17 ± 0.02 µM), good anti-TNF-α activity (EC50 = 0.19 ± 0.10 µM), remarkable selectivity profile, and good skin permeability. The topical treatment of 7b-1 resulted in the significant benefits of pharmacological intervention in a DNCB-induced atopic dermatitis-like mice model, demonstrating its potential for the development of novel antiatopic dermatitis agents.

Induced Mesenchymal Stem Cells-Small Extracellular Vesicles Alleviate Post-stroke Cognitive Impairment by Rejuvenating Senescence of Neural Stem Cells.

Ischemic stroke is typified by hypoxia and a cascade of pathophysiological events, including metabolic dysfunction, ionic dysregulation, excitotoxicity, inflammatory infiltration, and oxidative stress. These ultimately result in neuronal apoptosis or necrosis with constrained neuroregenerative capabilities. In this study, neural stem cells (NSCs) under conditions of oxygen-glucose deprivation (OGD) in vitro and following middle cerebral artery occlusion (MCAO) in vivo were explored. Transcriptome sequencing revealed a decline in NSC differentiation and neurogenesis after OGD exposure, which was related to cellular senescence. This observation was corroborated by increased senescence markers in the MCAO mouse model, reduction in NSC numbers, and decline in neurogenesis. Importantly, iMSC-sEVs (induced mesenchymal stem cells-small extracellular vesicles) have the therapeutic potential to alleviate NSC senescence and rejuvenate their regenerative capacities both in vitro and in vivo. Moreover, iMSC-sEVs contribute to the recovery of cognitive function and synapse loss caused by MCAO.

Insights into PM2.5 pollution of four small and medium-sized cities in Chinese representative regions: Chemical compositions, sources and health risks.

Fine particles (PM2.5) pollution is still a severe issue in some cities in China, where the chemical characteristics of PM2.5 remain unclear due to limited studies there. Herein, we focused on PM2.5 pollution in small and medium-sized cities in key urban agglomerations and conducted a comprehensive study on the PM2.5 chemical characteristics, sources, and health risks. In the autumn and winter of 2019-2020, PM2.5 samples were collected simultaneously in four small and medium-sized cities in four key regions: Dingzhou (Beijing-Tianjin-Hebei region), Weinan (Fenwei Plain region), Fukang (Northern Slope of the Tianshan Mountain region), and Bozhou (Yangtze River Delta region). The results showed that secondary inorganic ions (43.1 %-67.0 %) and organic matter (OM, 8.6 %-36.4 %) were the main components of PM2.5 in all the cities. Specifically, Fukang with the most severe PM2.5 pollution had the highest proportion of SO42- (31.2 %), while the dominant components in other cities were NO3- and OM. The Multilinear Engine 2 (ME2) analysis identified five sources of PM2.5 in these cities. Coal combustion contributed most to PM2.5 in Fukang, but secondary sources in other cities. Combined with chemical characteristics and ME2 analysis, it was preliminarily determined that the primary emission of coal combustion had an important contribution to high SO42- in Fukang. Potential source contribution function (PSCF) analysis results showed that regional transport played an important role in PM2.5 in Dingzhou, Weinan and Bozhou, while PM2.5 in Fukang was mainly affected by short-range transport from surrounding areas. Finally, the health risk assessment indicated Mn was the dominant contributor to the total non-carcinogenic risks and Cr had higher carcinogenic risks in all cities. The findings provide a scientific basis for formulating more effective abatement strategies for PM2.5 pollution.

Transforming waste brake pads from automobiles into Nano-Catalyst: Synergistic Fe-C-Cu triple sites for efficient fenton-like oxidation of organic pollutants.

The arbitrary disposal of used brake pads from motor vehicles has resulted in severe heavy metal pollution and resource wastage, highlighting the urgent need to explore the significant untapped potential of these discarded materials. In this study, The in-situ growth of highly dispersed Fe2O3 nanocrystals was achieved by simple oxidation annealing of brake pad debris(BPD). Interestingly, Cu remained unoxidized and acted as a "valence state transformation bridge of Fe2O3" to construct the "triple Fe-C-Cu sites". The Fenton degradation experiment of pollutants was conducted under constant temperature conditions at 40 °C, a stirring rate of 1300 rpm, a pH value of 3, a catalyst dosage of 0.5 g/L, pollutant dosage ranging from 50 to 400 mg/L, and H2O2 dosage of 0.25 g/L. Experimental results showed that BPD treated at 300 °C for 2 h exhibited optimal Fenton-like oxidation activity, achieving rapid degradation of over 90 % of refractory antibiotics, such as tetracycline and ciprofloxacin, in organic wastewater within 10 min. This remarkable performance was mainly attributed to the synergistic effect of "Fe-C-Cu triple sites", where the electron-donating role of C in the Fe-C and Cu-C interfaces facilitated the conversion of the Fe(III) to Fe(II) and Cu(II) to Cu(I). In addition, the ability of Cu2+ to accept electrons at the Fe-Cu interface promoted the transition from Fe (II) to Fe (III). This "balance of electron gain and loss" accelerated the interfacial electron transfer and the recycle of dual Fenton sites, Fe(II)/Fe(III) and Cu(I)/Cu(II), to generate more ·OH from H2O2. Therefore, this strategy of functionalizing BPD as Fenton-like catalysts without the addition of external Fe provides intriguing prospects for understanding the construction of Fe-based Fenton catalysts and resource utilization of Fe-containing solid waste materials.

Characterization of ultrasound-assisted covalent binding interaction between ß-lactoglobulin and dicaffeoylquinic acid: Great potential for the curcumin delivery.

The low bioavailability and poor gastrointestinal instability of curcumin hampers its application in pharmaceutical and food industries. Thus, it is essential to explore efficient carrier (e.g. a combination of polyphenols and proteins) for food systems. In this study, covalent ß-lactoglobulin (LG)-dicaffeoylquinic acids (DCQAs) complexes were prepared by combining ultrasound and free radical induction methods. Covalent interactions between LG and DCQAs were confirmed by analyzing reactive groups. Variations in secondary or tertiary structure and potential binding sites of covalent complexes were explored using Fourier transform infrared spectroscopy and circular dichroism. Results showed that the ß-sheet content decreased and the unordered content increased significantly (P < 0.05). The embedding rate of curcumin in prepared LG-DCQAs complexes using ultrasound could reach 49 % - 62 %, proving that complexes could embed curcumin effectively. This study highlights the benefit of ultrasound application in fabrication of protein-polyphenol complexes for delivering curcumin.

Coupling capillary electrophoresis with mass spectrometry for the analysis of oxidized phospholipids in human high-density lipoproteins.

The oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (ox-PAPC) products in human high-density lipoproteins (HDLs) were investigated by low-flow capillary electrophoresis-mass spectrometry (low-flow CE-MS). To accelerate the optimization, native PAPC (n-PAPC) standard was first analyzed by a commercial CE instrument with a photodiode array detector. The optimal separation buffer contained 60% (v/v) acetonitrile, 40% (v/v) methanol, 20 mM ammonium acetate, 0.5% (v/v) formic acid, and 0.1% (v/v) water. The selected separation voltage and capillary temperature were 20 kV and 23°C. The optimal CE separation buffer was then used for the low-flow CE-MS analysis. The selected MS conditions contained heated capillary temperature (250°C), capillary voltage (10 V), and injection time (1 s). No sheath gas was used for MS. The linear range for n-PAPC was 2.5-100.0 µg/mL. The coefficient of determination (R2 ) was 0.9918. The concentration limit of detection was 1.52 µg/mL, and the concentration limit of quantitation was 4.60 µg/mL. The optimal low-flow CE-MS method showed good repeatability and sensitivity. The ox-PAPC products in human HDLs were determined based on the in vitro ox-PAPC products of n-PAPC standard. Twenty-one ox-PAPC products have been analyzed in human HDLs. Uremic patients showed significantly higher levels of 15 ox-PAPC products than healthy subjects.

Structure-based design of potent FABP4 inhibitors with high selectivity against FABP3.

Fatty-acid binding protein 4 (FABP4) presents an attractive target for therapeutic intervention in metabolic and inflammatory diseases in recent years. However, highly similar three-dimensional structures and fatty acid binding ability of multiple FABP family members pose a significant challenge in design of FABP4-selective inhibitors. Particularly, inhibition of FABP3 raises safety concerns such as cardiac dysfunction and exercise intolerance. Here, we reported the discovery of new FABP4 inhibitors with high selectivity over FABP3 by exploiting the little structural difference in the ligand binding pockets of FABP4 and FABP3. On the basis of our previously reported FABP4 inhibitors with nanomolar potency, different substituents were further introduced to perfectly occupy two sub-pockets of FABP4 that are distinct from those of FABP3. Remarkably, a single methyl group introduction leads to the discovery of compound C3 that impressively exhibits a 601-fold selectivity over FABP3 when maintained nanomolar binding affinity for FABP4. Moreover, C3 also shows good metabolic stability and potent cellular anti-inflammatory activity, making it a promising inhibitor for further development. Therefore, the present study highlights the utility of the structure-based rational design strategy for seeking highly selective and potent inhibitors of FABP4 and the importance of identifying the appropriate subsite as well as substituent for gaining the desired selectivity.

Characterization and comparison of carboxymethylation and TEMPO-mediated oxidation for polysaccharides modification.

In this study, carboxymethylation and TEMPO-mediated oxidation were compared for their ability to introduce carboxyl groups to polysaccharides, using cellulose and chitin as model polysaccharides. The carboxyl group contents and changes in the molecular weight of carboxymethylated and TEMPO-oxidized cellulose/chitin were measured. The results revealed that carboxymethylation achieved higher carboxyl group contents, with values of 4.99 mmol/g for cellulose and 4.46 mmol/g for chitin, whereas for TEMPO-oxidized cellulose and chitin, the values were 1.64 mmol/g and 1.12 mmol/g, respectively. As a consequence of TEMPO-mediated oxidation, polysaccharides underwent degradation, leading to a decrease in the molecular weight of 42.46 % for oxidized cellulose and 64.5 % for oxidized chitin. Additionally, the crystallinity of carboxymethylated polysaccharides decreased with an increase in the carboxyl group contents, whereas that of TEMPO-oxidized polysaccharides remained unchanged. Furthermore, TEMPO-mediated oxidation selectively oxidized C6 primary hydroxyls, while carboxylmethylation converted all the hydroxyl groups on the polysaccharides.

Magnetic macroporous chitin microsphere as a support for covalent enzyme immobilization.

In this study, a novel magnetic macroporous chitin microsphere (MMCM) was developed for enzyme immobilization. Chitin nanofibers were prepared and subsequently subjected to self-assembly with magnetic nanoparticles and PMMA (polymethyl methacrylate). Following this, microspheres were formed through spray drying, achieving a porous structure through etching. The MMCM serves as an effective support for immobilizing enzymes, allowing for their covalent immobilization both on the microsphere's surface and within its pores. The substantial surface area resulting from the porous structure leads to a 2.1-fold increase in enzyme loading capacity compared to non-porous microspheres. The MMCM enhances stability of the immobilized enzymes under various pH and temperature conditions. Furthermore, after 20 days of storage at 4 °C, the residual activity of the immobilized enzyme was 2.93 times that of the free enzyme. Even after being recycled 10 times, the immobilized enzyme retained 56.7 % of its initial activity. It's noteworthy that the active sites of the enzymes remained unchanged after immobilization using the MMCM, and kinetic analysis revealed that the affinity of the immobilized enzymes rivals that of the free enzymes.

Ent-labdane-type diterpene glycosides obtained from Rubus chingii Hu and their inhibitory effects on PDE5A activity.

In this study, 16 new ent-labdane-type diterpene glycosides, designated as goshonosides J1-J16 (1-16), along with nine previously known diterpene glycosides (17-25) were extracted from the fruits of Rubus chingii Hu. The structures of goshonosides J1-J16 were elucidated using various analytical techniques, such as nuclear magnetic resonance, electron capture detector ECD, high-resolution electrospray ionization mass spectrometry HREIMS, single-crystal X-ray diffraction, and hydrolysis. Furthermore, the isolates' efficacy in inhibiting the activity of phosphodiesterase type 5 A was evaluated. Goshonosides J1, J2, and G effectively inhibited the activity of the aforementioned enzyme (IC50 values: 6.15 ± 1.76, 3.27 ± 0.65, and 9.61 ± 2.36 µM, respectively). Our findings highlight the remarkable structural diversity of bioactive compounds in R. chingii Hu and offer insights into the use of this shrub.

A reusable fiber-embedded microfluidic chip for rapid and sensitive on-site detection of kanamycin residues in water environments.

The overuse and abuse of antibiotics have led to increased pollution in water environments. Thus, it is crucial to develop a rapid, high-frequency, and cost-effective method for on-site detection of antibiotics. In this regard, a reusable fiber-embedded microfluidic chip was constructed by combining a microfluidic chip with a functionalized fiber bioprobe that served as both a biorecognition element and an optical transducer. The fiber-embedded microfluidic chip enabled the quantitative detection of kanamycin (KANA) by integrating a portable all-fiber evanescent wave fluorescence detection device. Under optimized conditions, quantitative KANA detection was achieved with a detection limit of 0.03 µg L-1 and a linear detection range of 0.21-10.3 µg L-1. The accurate detection of KANA in various water samples can be completed within 25 min without pretreatment. The functionalized fiber-embedded microfluidic chip could be reused more than 200 times without significant performance loss. To demonstrate its suitability for practical applications, the fiber-embedded microfluidic chip was used to investigate KANA residues in surface waters obtained from the Qinghe River in Beijing, China. The results were compared with those of a traditional enzyme-linked immunosorbent assay, which showed a high correlation. Compared to conventional optical microfluidic chips, the proposed fiber-embedded microfluidic chip has several advantages, including its ease of use, miniaturization, cost-effectiveness, reusability, and high flexibility. It is an ideal alternative for rapid, sensitive on-site detection of antibiotics and other trace substances in environmental, food, and medical fields.

Mediating oxidative stress through the Palbociclib/miR-141-3p/STAT4 axis in osteoporosis: a bioinformatics and experimental validation study.

Osteoporosis is a common bone disease characterized by loss of bone mass, reduced bone strength, and deterioration of bone microstructure. ROS-induced oxidative stress plays an important role in osteoporosis. However, the biomarkers and molecular mechanisms of oxidative stress are still unclear. We obtained the datasets from the Gene Expression Omnibus (GEO) database, and performed differential analysis, Venn analysis, and weighted correlation network analysis (WGCNA) analysis out the hub genes. Then, the correlation between inflammatory factors and hub genes was analyzed, and a Mendelian randomization (MR) analysis was performed on cytokines and osteoporosis outcomes. In addition, "CIBERSORT" was used to analyze the infiltration of immune cells and single-cell RNA-seq data was used to analyze the expression distribution of hub genes and cell-cell communications. Finally, we collected human blood samples for RT-qPCR and Elisa experiments, the miRNA-mRNA network was constructed using the miRBase database, the 3D structure was predicted using the RNAfold, Vfold3D database, and the drug sensitivity analysis was performed using the RNAactDrug database. We obtained three differentially expressed genes associated with oxidative stress: DBH, TAF15, and STAT4 by differential, WGCNA clustering, and Venn screening analyses, and further analyzed the correlation of these 3 genes with inflammatory factors and immune cell infiltration and found that STAT4 was significantly and positively correlated with IL-2. Single-cell data analysis showed that the STAT4 gene was highly expressed mainly in dendritic cells and monocytes. In addition, the results of RT-qPCR and Elisa experiments verified that the expression of STAT4 was consistent with the previous analysis, and a significant causal relationship between IL-2 and STAT4 SNPs and osteoporosis was found by Mendelian randomization. Finally, through miRNA-mRNA network and drug sensitivity analysis, we analyzed to get Palbociclib/miR-141-3p/STAT4 axis, which can be used for the prevention and treatment of osteoporosis. In this study, we proposed the Palbociclib/miR-141-3p/STAT4 axis for the first time and provided new insights into the mechanism of oxidative stress in osteoporosis.

Drug repurposing and structure-based discovery of new PDE4 and PDE5 inhibitors.

Phosphodiesterase-4 (PDE4) and PDE5 responsible for the hydrolysis of intracellular cAMP and cGMP, respectively, are promising targets for therapeutic intervention in a wide variety of diseases. Here, we report the discovery of novel, drug-like PDE4 inhibitors by performing a high-throughput drug repurposing screening of 2560 approved drugs and drug candidates in clinical trial studies. It allowed us to identify eight potent PDE4 inhibitors with IC50 values ranging from 0.41 to 2.46 µM. Crystal structures of PDE4 in complex with four compounds, namely ethaverine hydrochloride (EH), benzbromarone (BBR), CX-4945, and CVT-313, were further solved to elucidate molecular mechanisms of action of these new inhibitors, providing a solid foundation for optimizing the inhibitors to improve their potency as well as selectivity. Unexpectedly, selectivity profiling of other PDE subfamilies followed by crystal structure determination revealed that CVT-313 was also a potent PDE5 inhibitor with a binding mode similar to that of tadalafil, a marketed PDE5 inhibitor, but distinctively different from the binding mode of CVT-313 with PDE4. Structure-guided modification of CVT-313 led to the discovery of a new inhibitor, compound 2, with significantly improved inhibitory activity as well as selectivity towards PDE5 over PDE4. Together, these results highlight the utility of the drug repurposing in combination with structure-based drug design in identifying novel inhibitors of PDE4 and PDE5, which provides a prime example for efficient discovery of drug-like hits towards a given target protein.

Metalloborospherenes with a Stabilized Classical Fullerene-like Borospherene B40 Act as Nonlinear Optical Switches, Electron Reservoirs, Molecular Capacitors, and Molecular Reactors.

Using a new method of η5-Li and η6-Mg atoms capping the faces of the classical fullerene-like borospherene Td B40, we theoretically predict an exohedral metalloborospherene Td Mg10Li12&B40 molecule. Remarkably, a newfangled endoexo cage isomerism is proposed. Further, embedding Mg atoms in the Td B40 cage forms endohedral derivatives. Due to the intramolecular pull-push electron transfer relay, these obtained molecules possess unequal multilayered and alternant spherical charge distribution. The outer is an excess electron layer, bringing a molecular nonlinear switch character and an electron reservoir behavior with strong electron-donating and -accepting abilities. The middle (Mg2+)10(Li+)12 and the outer layers together constitute an electric double layer, presenting the behavior of a molecular capacitor where the electronic charge-discharge process occurs in the outer excess electron layer. The inner part is an empty cage B4026- with a strong negative electric field. The valence electrons of the embedded Mg atoms are transformed into new excess electrons and added in the outer excess electron layer, also exhibiting the charging behavior of the molecular capacitor. Considering the chemical reaction in the inner cage, the embedded Mg atom is ionized, forming an Mg2+ cation and 2e under the strong negative electric field; meanwhile, 2e is powerfully pushed into the outer excess electron layer. This chemical process shows a generalized Coulomb explosion, and thus the exohedral metalloborospherene molecules with cage B4026- may act as molecular reactors. The new species mark the genesis of classical fullerene-like borospherene chemistry and stimulate their applications in molecular nonlinear optical and nanoelectronics.

Noteworthy perspectives on microglia in neuropsychiatric disorders.

Microglia are so versatile that they not only provide immune surveillance for central nervous system, but participate in neural circuitry development, brain blood vessels formation, blood-brain barrier architecture, and intriguingly, the regulation of emotions and behaviors. Microglia have a profound impact on neuronal survival, brain wiring and synaptic plasticity. As professional phagocytic cells in the brain, they remove dead cell debris and neurotoxic agents via an elaborate mechanism. The functional profile of microglia varies considerately depending on age, gender, disease context and other internal or external environmental factors. Numerous studies have demonstrated a pivotal involvement of microglia in neuropsychiatric disorders, including negative affection, social deficit, compulsive behavior, fear memory, pain and other symptoms associated with major depression disorder, anxiety disorder, autism spectrum disorder and schizophrenia. In this review, we summarized the latest discoveries regarding microglial ontogeny, cell subtypes or state spectrum, biological functions and mechanistic underpinnings of emotional and behavioral disorders. Furthermore, we highlight the potential of microglia-targeted therapies of neuropsychiatric disorders, and propose outstanding questions to be addressed in future research of human microglia.

Exploring the training of chinese medical staff oriented to the need for clinical drug information services: from the perspective of drug information patients obtained and need.

BACKGROUND: There are some gaps between the training of drug information service competencies for medical staff and drug information patients need in China. OBJECTIVE: To investigate drug information patients obtained and need for further providing directions for the training of drug information service competencies among medical staff in China from patients' perspectives. METHODS: A face-to-face nationwide survey was conducted using a stratified sampling method. Data were analyzed descriptively using frequencies, percentages and mean. Several subgroup analyses using Chi-square tests were conducted to identify patients' need for drug information in China. RESULTS: A total of 1994 questionnaires from medical institutions in China were returned. Most of the drug information obtained by patients came from physicians, and different types of drug information were important to patients. Additionally, patients had different needs for drug information due to age, gender, diagnosis and treatment status, and education level. CONCLUSIONS: The training of medical staff needs to increase the presence of nurses and pharmacists in drug information services, enhance the awareness of "patient-centered" services, and improve the ability to provide information services specific to the characteristics of patients.

Discovery of novel cGAS inhibitors based on natural flavonoids.

Cyclic GMP-AMP synthase (cGAS) plays an important role in the inflammatory response. It has been reported that aberrant activation of cGAS is associated with a variety of immune-mediated inflammatory disorders. The development of small molecule inhibitors of cGAS has been considered as a promising therapeutic strategy for the diseases. Flavonoids, a typical class of natural products, are known for their anti-inflammatory activities. Although cGAS is closely associated with inflammation, the potential effects of natural flavonoid compounds on cGAS have been rarely studied. Therefore, we screened an in-house natural flavonoid library by pyrophosphatase (PPiase) coupling assay and identified novel cGAS inhibitors baicalein and baicalin. Subsequently, crystal structures of the two natural flavonoids in complex with human cGAS were determined, which provide mechanistic insight into the anti-inflammatory activities of baicalein and baicalin at the molecular level. After that, a virtual screening based on the crystal structures of baicalein and baicalin in complex with human cGAS was performed. As a result, compound C20 was identified to inhibit both human and mouse cGAS with IC50 values of 2.28 and 1.44 µM, respectively, and its detailed interactions with human cGAS were further revealed by the X-ray crystal structure determination. These results demonstrate the potential of natural products used as hits in drug discovery and provide valuable hints for further development of cGAS inhibitors.