Controlled Sequential Doping of Metal Nanocluster.

Atomically precise doping of metal nanoclusters provides excellent opportunities not only for subtly tailoring their properties but also for in-depth understanding of composition (structure)-property correlation of metal nanoclusters and has attracted increasing interest partly due to its significance for fundamental research and practical applications. Although single and multiple metal atom doping of metal nanoclusters (NCs) has been achieved, sequential single-to-multiple metal atom doping is still a big challenge and has not yet been reported. Herein, by introducing a second ligand, a novel multistep synthesis method was developed, controlled sequential single-to-multiple metal atom doping was successfully achieved for the first time, and three doped NCs Au25Cd1(p-MBT)17(PPh3)2, Au18Cd2(p-MBT)14(PPh3)2, and [Au19Cd3(p-MBT)18]- (p-MBTH: para-methylbenzenethiol) were obtained, including two novel NCs that were precisely characterized via mass spectrometry, single-crystal X-ray crystallography, and so forth. Furthermore, sequential doping-induced evolutions in the atomic and crystallographic structures and optical and catalytic properties of NCs were revealed.

A mixed-dimensional quasi-1D BiSeI nanowire-2D GaSe nanosheet p-n heterojunction for fast response optoelectronic devices.

Due to the unique combination configuration and the formation of a built-in electric field, mixed-dimensional heterojunctions present fruitful possibilities for improving the optoelectronic performances of low-dimensional optoelectronic devices. However, the response times of most photodetectors built from mixed-dimensional heterojunctions are within the millisecond range, limiting their applications in fast response optoelectronic devices. Herein, a mixed-dimensional BiSeI/GaSe van der Waals heterostructure is designed, which exhibits visible light detection ability and competitive photoresponsivity of 750 A W-1 and specific detectivity of 2.25 × 1012 Jones under 520 nm laser excitation. Excitingly, the device displays a very fast response time, e.g., the rise time and decay time under 520 nm laser excitation are 65 µs and 190 µs, respectively. Our findings provide a prospective approach to mixed-dimensional heterojunction photodetection devices with rapid switching capabilities.

Nanoclusterzyme for Dual Colorimetric Sensings: A Case Study on [Au14 (Dppp)5 I4 ]2.

The enzymatic activity of atomically precise metal nanoclusters has recently been recognized; however, the number of nanoclusterzymes is very small. Besides, the applications of nanoclusterzyme wait to be explored. Herein, a novel nanoclusterzyme is synthesized and its structure is majorly resolved by single-crystal X-ray diffraction and mass spectrometry, which reveal that the nanocluster consists of an Au13 icosahedron capped by an exterior shell including four I, three Dppp (1,3-bis(diphenylphosphino) propane) ligands, and a rarely reported Dppp-Au-Dppp handle staple, which contributes a lot to the enzyme activity of [Au14 (Dppp)5 I4 ]2+ nanocluster. The as-obtained nanocluster can catalyze oxygen to O2 •- under visible light irradiation with a specific activity up to 0.182 U·mg-1 and lead to the blue color of 3,3',5,5'-tetramethylbenzidine (TMB) in both solution and solid states. With the addition of acetylcholinesterase (AChE), the blue color of (Au14  + TMB) solution system disappears due to the nanoclusterzyme activity inhibition, but the further addition of organophosphorus pesticides (OPs) into the above mixture can restore the nanoclusterzyme and recover the blue color. Based on the color turn-off and on, the various nanoclusterzyme-containing systems are used to colorimetrically sense AChE and OPs with the detection limits reaching 0.04 mU·mL-1 and 0.02 ng·mL-1 , respectively.

Adaptive control for downhole nuclear magnetic resonance excitation.

Nuclear magnetic resonance (NMR) measurements are performed with the pulse sequence and acquisition parameters set by the operator, which cannot be adjusted in real time according to sample characteristics. In one acquisition cycle, usually thousands of high-power pulses are transmitted and thousands of echo points are acquired. The power consumption cause the RF amplifier to overheat, and large amounts of acquired data may be invalid. Therefore, the optimization of excitation and acquisition processes is necessary to improve measurement efficiency. We explore a scheme for the real-time measurement of the samples by adaptively regulating the pulse sequence, which adapts the variable TE pulse sequence as the reconnaissance mode. The appropriate pulse sequence and reasonable parameters (NE, TE) can be selected according to the relaxation characteristics of the samples.This adaptive control strategy has great significance in guiding both dynamic and static measurements, and it is especially suitable for occasions where low magnetic field gradients and diffusion terms can be ignored. We also design a test circuit for adaptive control, which has the function of automatic parameter adjustment. By adjusting parameters such as the number of refocusing pulses, echo spacing, etc., the effective measurement of the samples can be achieved in practice.

A Randomized Study of Rigid Video Stylet versus Macintosh Laryngoscope for Double-Lumen Endobronchial Tube Intubation Assistance in Thoracoscopic Pulmonary Surgery.

Double-lumen endobronchial tube (DLT) intubation is more challenging than single-lumen tube intubation is, and the rigid video stylet (RVS) is one of the tools that has emerged to deal with this demanding intubation procedure. We evaluated whether the UE® RVS can shorten the DLT intubation time and improve the first-attempt intubation success rate compared with that of Macintosh laryngoscope (ML). A total of 130 participants scheduled to undergo thoracoscopic pulmonary surgeries were enrolled. They were randomized to receive either ML- or RVS-assisted DLT intubation. The primary outcomes were the intubation time and first-attempt intubation success rate. The secondary outcomes were the overall intubation success rate, mean arterial pressure, postoperative sore throat (POST), and postoperative hoarseness at 1 h and 24 h. Compared with the ML group, the intubation time was significantly shorter in the RVS group (p < 0.001; 30.82 ± 10.61 vs. 39.62 ± 6.54 s), however, the first-attempt success rate was significantly lower (p = 0.048; 83.08% vs. 95.16%). The POST at 1 h was less severe in the RVS group (p = 0.021). No significant differences were found for the other indicators. Among the patients with normal airways, the UE® RVS can achieve faster DLT intubation and decrease the severity of a POST at 1 h, although it was associated with a lower first-attempt intubation success rate.

Research trends in ferroptosis since the origin of the concept: A bibliometric analysis.

Ferroptosis is a newly characterized form of regulated cell death. This bibliometric analysis identified the scientific output, leading institutions and research teams, current research hotspots and trends in research on ferroptosis since the origin of the concept. We searched the Science Citation Index Expanded of Web of Science Core Collection for papers on ferroptosis up to 3 June 2022. The acquired data were analysed and visualized by Bibliometrix package and VOSviewer. The study ultimately included 3511 relevant papers, and annual production in this field has grown rapidly in recent years. Institutions and scholars from China contributed the most work, but the impact of their research was much less than that of the United States. Prof. Brent R. Stockwell's team from Columbia University in the United States has a very strong academic influence in the field. Front Cell Dev Biol published the most papers in the field of ferroptosis. As the keywords of the papers in this field changed from the most numerous 'oxidative stress', 'cell-death', 'iron', 'expression', and 'lipid-peroxidation', to 'prognosis', 'immunotherapy', 'progression', 'tumour microenvironment', and 'colorectal cancer', the hotspot of ferroptosis research is gradually shifting from basic research to clinical translational research. The mechanism of tumour formation and treatment will become the frontier in the field of ferroptosis research in the future.

Structure Evolution and Properties Modification for Reaction-Bonded Silicon Carbide.

Complex structure reaction-bonded silicon carbide (RB-SiC) can be prepared by reactive melt infiltration (RMI) and digital light processing (DLP). However, the strength and modulus of RB-SiC prepared by DLP are not sufficient, due to its low solid content (around 40 vol.%), compared with the traditional fabrication techniques (solid content > 60 vol.%). With this understanding, a new method to improve the properties of RB-SiC was proposed, by the impregnation of composite precursor into the porous preform. The composite precursor was composed of phenolic (PF) resin and furfuryl alcohol (FA). PF and FA were pyrolyzed at 1850 °C to obtain amorphous carbon and graphite into the porous preform, respectively. The effects of multiphase carbon on the microstructure and performance of RB-SiC was studied. When the mass ratio of PF to FA was 1/4, the solid content of RB-SiC increased from 40 vol.% to 68.6 vol.%. The strength, bulk density and modulus were 323.12 MPa, 2.94 g/cm3 and 348.83 Gpa, respectively. This method demonstrated that the reaction process between liquid Si and carbon could be controlled by the introduction of multiphase carbon into the porous preforms, which has the potential to regulate the microstructure and properties of RB-SiC prepared by additive manufacturing or other forming methods.

Characterization of Fatty Acid Metabolism in Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Fatty acid metabolism takes part in malignancy progression. However, the roles fatty acid metabolism plays in LUAD are still unclear. Methods: The transcriptomic and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were extracted. ssGSEA, WGCNA, univariable Cox regression, and LASSO Cox regression analyses were performed to identify the fatty acid metabolism-related genes which influenced the overall survival (OS) and build a fatty acid-related risk score (FARS) model. A nomogram was established based on the FARS and other clinicopathological features, and ROC and calibration plots were used to validate the prediction accuracy. The tumor microenvironment (TME) of patients with high and low FARS was compared. Results: A total of 38 genes were identified to be independently related to the survival outcome and put into a FARS model. High FARS patients exhibited significantly worse OS. The nomogram included the FARS and pathological stage, and the AUC of the nomogram predicting 1-, 2-, 3-, 4-, and 5-year OS was 0.789, 0.807, 0.798, 0.809, and 0.753, respectively. Calibration plots also indicated good accuracy. Moreover, the samples of the high FARS had higher expression of PDL1. Conclusion: We constructed a FARS model which could accurately predict the survival outcome of the LUAD patients. The genes of the FARS are related to the tumor microenvironment and patients with high FARS can potentially benefit more from anti-PD1/PDL1 immunotherapy. In addition, the mechanisms of the genes in the FARS affecting prognosis are worthy of further research to develop new gene-targeted drugs.

Study on the Action Mechanism of the Yifei Jianpi Tongfu Formula in Treatment of Colorectal Cancer Lung Metastasis Based on Network Analysis, Molecular Docking, and Experimental Validation.

Objective: The lung is the second most common site of colorectal cancer (CRC) metastasis. This study aims to investigate the therapeutic effects and potential action mechanisms of Yifei Jianpi Tongfu formula (YJTF) in CRC lung metastasis in a comprehensive and systematic way by network analysis, molecular docking, and experimental verification. Methods: The main ingredients in YJTF were screened from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID), and the disease-related targets from the Online Mendelian Inheritance in Man (OMIM) and GeneCards and the compound-related targets from SwissTargetPrediction were collected. Then, Metascape was used for pathway annotation and enrichment analysis, and meanwhile, a protein-protein interaction (PPI) network was constructed. Molecular docking was carried out to investigate interactions between the active compounds and the potential targets. The in vivo effect of YJTF on CRC lung metastasis was observed in a tail vein injection mouse model. Results: A total of 243 active compounds and 81 disease-related targets of YJTF were selected for analysis. The results of multiple network analysis showed that the core targets of YJTF were enriched onto various cancer-related pathways, especially focal adhesion and adherens junction. The results of molecular docking demonstrated that all core compounds (quercetin, kaempferol, luteolin, apigenin, and isorhamnetin) were capable of binding with AKT1, EGFR, SRC, ESR1, and PTGS2. Experimental validation in vivo demonstrated that YJTF combined with oxaliplatin could significantly reduce the number of lung metastases and improve the quality of life in mice. Further research suggested that YJTF inhibited CRC lung metastasis probably by modulating epithelial-to-mesenchymal transition (EMT). Conclusions: According to the analysis, YJTF can be considered as an effective adjuvant therapy for CRC lung metastasis.

Developmental Trends and Research Hotspots in Bronchoscopy Anesthesia: A Bibliometric Study.

Background: This study discusses the developmental trends and research hotspots in bronchoscopy anesthesia in the past six decades. Methods: The original and review articles published from 1975 to June 2021 related to bronchoscopy anesthesia were retrieved from the Web of Science Core Collection (WoSCC). Three different scientometric tools (CiteSpace, VOSviewer, and Bibliometrix) were used for this comprehensive analysis. Results: There was a substantial increase in the research on bronchoscopy anesthesia in recent years. A total of 1,270 publications were retrieved up to June 25, 2021. Original research articles were 1,152, and reviews were 118, including 182 randomized controlled trials (RCTs). These publications were cited a total of 25,504 times, with a mean of 20.08 citations per publication. The US had the largest number of publications (27.6%) and the highest H-index of 44. The sum of publications from China ranked second (11.5%), with an H-index of 17. Keyword co-occurrence and references co-citation visual analysis showed that the use of sedatives such as dexmedetomidine in the process of bronchoscopy diagnosis and treatment was gradually increasing, indicating that bronchoscopy anesthesia was further progressing toward safety and comfort. Conclusion: Based on a bibliometric analysis of the publications over the past decades, a comprehensive analysis indicated that the research of bronchoscopy anesthesia is in a period of rapid development and demonstrated the improvement of medical instruments and surgical options that have significantly contributed to the field of bronchoscopy anesthesia. The data would provide future directions for clinicians and researchers in relation to bronchoscopy anesthesia.

Role of Pneumonectomy in T1-4N2M0 Non-Small Cell Lung Cancer: A Propensity Score Matching Analysis.

Background: N2 stage disease constitutes approximately 20%-30% of all non-small cell lung cancer (NSCLC). Concurrently, surgery remains the first-choice treatment for patients with N2 NSCLC if feasible. However, the role of pneumonectomy in N2 NSCLC has rarely been investigated and remains controversial. Methods: We enrolled 26,798 patients with T1-4N2M0 NSCLC (stage IIIA/IIIB) from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. We compared the overall survival (OS) and cancer-specific survival (CSS) between patients who received pneumonectomy and those who did not receive surgery. The Kaplan-Meier method, Cox regression analyses, and propensity score matching (PSM) were applied to demonstrate the effect of pneumonectomy. Results: Patients receiving pneumonectomy had a significantly better OS and CSS than those without pneumonectomy both before [adjusted-HR (95% CI): 0.461 (0.425-0.501) for OS, 0.444 (0.406-0.485) for CSS] and after PSM [adjusted-HR (95% CI): 0.499 (0.445-0.560) for OS, 0.457 (0.405-0.517) for CSS] with all p-values <0.001. Subgroup analysis demonstrated concordant results stratified by demographic or clinicopathological variables. In sensitivity analysis, no significant difference was observed between patients receiving single pneumonectomy and chemoradiotherapy without surgery in OS and CSS both before [unadjusted-HR (95% CI): 1.016 (0.878-1.176) for OS, 0.934 (0.794-1.099) for CSS, p = 0.832] and after PSM [unadjusted-HR (95% CI): 0.988 (0.799-1.222) for OS, 0.938 (0.744-1.182) for CSS] with all p-values >0.4. Conclusion: For patients with T1-4N2M0 NSCLC (stage IIIA/IIIB), pneumonectomy is an independent protective factor of OS and should be considered when applicable.

Magnesium Hydride Ameliorates Endotoxin-Induced Acute Respiratory Distress Syndrome by Inhibiting Inflammation, Oxidative Stress, and Cell Apoptosis.

Acute respiratory distress syndrome (ARDS) causes uncontrolled pulmonary inflammation, resulting in high morbidity and mortality in severe cases. Given the antioxidative effect of molecular hydrogen, some recent studies suggest the potential use of molecular hydrogen as a biomedicine for the treatment of ARDS. In this study, we aimed to explore the protective effects of magnesium hydride (MgH2) on two types of ARDS models and its underlying mechanism in a lipopolysaccharide (LPS)-induced ARDS model of the A549 cell line. The results showed that LPS successfully induced oxidative stress, inflammatory reaction, apoptosis, and barrier breakdown in alveolar epithelial cells (AEC). MgH2 can exert an anti-inflammatory effect by down-regulating the expressions of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). In addition, MgH2 decreased oxidative stress by eliminating intracellular ROS, inhibited apoptosis by regulating the expressions of cytochrome c, Bax, and Bcl-2, and suppressed barrier breakdown by up-regulating the expression of ZO-1 and occludin. Mechanistically, the expressions of p-AKT, p-mTOR, p-P65, NLRP3, and cleaved-caspase-1 were decreased after MgH2 treatment, indicating that AKT/mTOR and NF-κB/NLRP3/IL-1ß pathways participated in the protective effects of MgH2. Furthermore, the in vivo study also demonstrated that MgH2-treated mice had a better survival rate and weaker pathological damage. All these findings demonstrated that MgH2 could exert an ARDS-protective effect by regulating the AKT/mTOR and NF-κB/NLRP3/IL-1ß pathways to suppress LPS-induced inflammatory reaction, oxidative stress injury, apoptosis, and barrier breakdown, which may provide a potential strategy for the prevention and treatment of ARDS.

A bibliometric analysis of autophagy in lung diseases from 2012 to 2021.

Background: Autophagy refers to the process in which cells wrap their damaged organelles or unwanted proteins into a double-membrane structure and direct them to lysosomes for degradation. Autophagy can regulate many lung diseases such as pulmonary hypertension, acute lung injury, and lung cancer. However, few bibliometric studies on autophagy are available. The aim of the present study was to clarify the role of autophagy in lung diseases by bibliometric analysis. Methods: Publications were retrieved from the 2012-2021 Science Citation Index Expanded of Web of Science Core Collection on 20 September 2022. Bibliometrix package in R software was used for data retrieval. VOSviewer and CiteSpace were used to visualize the research focus and trend regarding the effect of autophagy on lung disease. Results: A total of 4,522 original articles and reviews on autophagy in lung diseases published between 2012 and 2021 were identified. China had the largest number of published papers and citations, whereas the United States (US) ranked first in the H-index and G-index. Moreover, cooperation network analysis showed close cooperation between the US, China, and some European countries, and the top 10 affiliates were all from these countries and regions. Bibliometric analysis showed that "autophagy" and "apoptosis" were the keywords with the highest frequency. During the past decade, most studies were concerned with basic research on pathways related to the regulatory role of autophagy in the inhibition and attenuation of lung diseases. Conclusion: The study of autophagy in lung diseases is still in the development stage. The information published in these articles has helped researchers understand further the hot spots and development trends in the field more and learn about the collaboration network information regarding authors, countries, and institutions, as well as the paper citation correlation. More studies have been performed to gain deeper insights into the pathogenesis of autophagy by focusing on the links and effects between various diseases. More recently, research in this field has paid increasing attention to the function of autophagy in COVID-19-related lung diseases.

Global Research Trends and Hotspots on Mitochondria in Acute Lung Injury from 2012-2021: A Bibliometric Analysis.

BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a clinical syndrome associated with mitochondria and lacks effective preventive and therapeutic measures. This bibliometric study aims to gain insight into the scientific findings regarding mitochondria in ALI/ARDS. METHODS: We retrieved the Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (WoSCC) for mitochondria in ALI/ARDS publications from 2012-2021. VOSviewer, CiteSpace (5.8. R3) and Bibliometrix (3.1.4) R package were used for further analysis and visualization. RESULT: A total of 756 English-language articles and reviews were identified. The annual number of publications presented a rapidly developing trend. China was the most productive and cited country, and the USA had the greatest impact. In the keyword co-occurring network, the terms "acute lung injury", "oxidative stress", "inflammation", "mitochondria" and "apoptosis" occurred most frequently. The co-citation network revealed that #1 mesenchymal stromal cell and #3 endothelial cell had the most bursts of citations. In addition, research hotspots have shifted from "potential therapeutic treatments" and "mitochondrial DNA (mtDNA)" to "endothelial cell" and "mesenchymal stromal cell (MSC)". CONCLUSION: This bibliometric analysis reveals the research directions and frontier hotspots of mitochondria in ALI/ARDS, which has shown a rapid growth trend in annual publication numbers. mtDNA, mitophagy, and apoptosis have been the most active research areas, while studies on mitochondrial transfer in stem cells have become a hot topic in recent years.

Global Trends in Research of Macrophages Associated With Acute Lung Injury Over Past 10 Years: A Bibliometric Analysis.

Acute lung injury (ALI) is an intractable disorder associated with macrophages. This bibliometric analysis was applied to identify the characteristics of global scientific output, the hotspots, and frontiers about macrophages in ALI over the past 10 years. We retrieved publications published from 2011 to 2020 and their recorded information from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC). Bibliometrix package was used to analyze bibliometric indicators, and the VOSviewer was used to visualize the trend and hotspots of researches on macrophages in ALI. Altogether, 2,632 original articles were reviewed, and the results showed that the annual number of publications (Np) concerning the role of macrophages in ALI kept increasing over the past 10 years. China produced the most papers, the number of citations (Nc) and H-index of the USA ranked first. Shanghai Jiaotong University and INT IMMUNOPHARMACOL were the most prolific affiliation and journal, respectively. Papers published by Matute-Bello G in 2011 had the highest local citation score (LCS). Recently, the keywords "NLRP3" and "extracellular vesicles" appeared most frequently. Besides, researches on COVID-19-induced ALI related to macrophages seemed to be the hotspot recently. This bibliometric study revealed that publications related to macrophages in ALI tend to increase continuously. China was a big producer and the USA was an influential country in this field. Most studies were mainly centered on basic researches in the past decade, and pathways associated with the regulatory role of macrophages in inhibiting and attenuating ALI have become the focus of attention in more recent studies. What is more, our bibliometric analysis showed that macrophages play an important role in COVID-19-induced ALI and may be a target for the treatment of COVID-19.

Silencing of circRNA circ_0001666 Represses EMT in Pancreatic Cancer Through Upregulating miR-1251 and Downregulating SOX4.

BACKGROUND: Pancreatic cancer (PC) is an aggressive malignancy and has a poor prognosis. Although emerging research has revealed that circular RNAs (circRNAs) are crucial modulators that control tumor development and metastasis, their functional involvement in PC has not been well characterized. Here, we examined whether and how circRNA circ_0001666 governs epithelial-mesenchymal transition (EMT) in PC. METHODS: We investigated the effects of circ_0001666 on EMT and PC cell invasion by gain- and loss-of-function assays. We also explored the mechanisms underlying the functions of circ_0001666 in PC cells. RESULTS: We found that circ_0001666 is highly expressed in PC tissues and PC cell lines. Patients with high circ_0001666 expression had shorter survival times. In vitro and in vivo experiments have demonstrated that upregulation of circ_0001666 facilitates PC cell proliferation, EMT and invasiveness, whereas knockdown of circ_0001666 exhibits opposite functions. Moreover, circ_0001666 is able to bind to miR-1251, thus increasing the expression of SOX4, which is a direct downstream effector of miR-1251. The oncogenic effects of circ_0001666 on EMT and PC cell invasion were rescued by miR-1251 overexpression. CONCLUSIONS: These results suggested that circ_0001666 acts as an oncogenic circRNA to promote EMT and invasion of PC cells through sponging miR-1251, and indicated that circ_0001666 could be explored as a potential therapeutic target for PC.

[Moxibustion improves learning-memory ability by promoting cellular autophagy and regulating autophagy-related proteins in hippocampus and cerebral cortex in APP/PS1 transgenic Alzheimer's disease mice].

OBJECTIVE: To observe the effect of moxibustion of acupoints of the Governor Vessel on the levels of cellular autophagy, ß amyloid protein (Aß) immunoactivity, and expression of LC3-Ⅰ， LC3-Ⅱ， p62 and p-P70S6K proteins in the hippocampal tissue of APPswe/PS1de9 (APP/PS1) double-transgenic Alzheimer's disease (AD) mice, so as to reveal its underlying mechanisms in improving AD. METHODS: APP/PS1 double-transgenic AD mice were randomly divided into AD model, moxibustion, autophagy-inducer (Rapamycin) and autophagy-inhibitor (3-MA)＋moxibustion groups (n＝10 in each group), and other 10 C57BL/6J male mice (the same age) were used as the normal control group. Herbal-cake (made of Chuanwu [Radix Aconiti Praeparata]) partitioned moxibustion was applied to "Baihui"(GV20), moxibustion was applied to "Fengfu"(GV16) and "Dazhui"(GV14), all for 20 min, once daily for 2 weeks, with one day's off between two weeks. For mice of the autophagy-inducer and 3-MA＋moxibustion groups, Rapamycin (2 mg•kg－1•d－1) and 3-MA (1.5 mg•kg－1•d－1) were separately administered by intraperitoneal injection for 2 weeks. The cognitive ability was examined by Morris water maze tests, and the ultrastructural changes (including autophagic lysosomes, etc.) of hippocampal neurons were observed by using transmission electron microscopy. The immunoactivity of cerebral cortex and hippocampal Amyloid ß peptide 1-42 (Aß1-42) was detected by immunohistochemistry, and the expression levels of hippocampal LC3-Ⅰ， LC3-Ⅱ， p62 and p-P70S6K proteins were detected by Western blot. RESULTS: After modeling, the escape latency of Morris water maze tasks was prolonged in the model group than in the normal control group (P<0.05) and obviously shortened in the moxibustion and autophagy-inducer groups (not the autophagy-inhibitor group) than in the model group (P<0.05). Results of transmission electron microscope showed deformed, irregular or atrophic neurons with rough and incomplete and fuzzy nuclear membrane, and decreased intracellular autophagosomes in the hippocampus in the model group, and partial irregular, atrophic neurons with more autophagic vesicles and lysosomes in the moxibustion group. The expression levels of Aß1-42 in both cerebral cortex and hippocampus tissues, and LC3-Ⅰ， p62 and p-P70S6K proteins in the hippocampus were consi-derably up-regulated in the model group relevant to the normal control group (P<0.01), and evidently down-regulated in both moxibustion and autophagy-inducer groups (not the autophagy-inhibitor group) than in the model group (P<0.01), while that of hippocampal LC3-Ⅱ protein and LC3-Ⅱ/Ⅰ ratio levels were obviously down-regulated in the model group relevant to the normal control group (P<0.01), and significantly up-regulated in both moxibustion and autophagy-inducer groups (not the autophagy-inhibitor group) than in the model group (P<0.01)．. CONCLUSION: Moxibustion can improve the cognitive ability of APP/PS1 double-transgenic AD mice, which is associated with its effects in promoting hip-pocampal and cerebral cortex autophagy level, and down-regulating the expression levels of Aß1-42, LC3-Ⅰ， p62 and p-P70S6K proteins in the hippocampus.

A Single Mutation Increases the Thermostability and Activity of Aspergillus terreus Amine Transaminase.

Enhancing the thermostability of (R)-selective amine transaminases (AT-ATA) will expand its application in the asymmetric synthesis of chiral amines. In this study, mutual information and coevolution networks of ATAs were analyzed by the Mutual Information Server to Infer Coevolution (MISTIC). Subsequently, the amino acids most likely to influence the stability and function of the protein were investigated by alanine scanning and saturation mutagenesis. Four stabilized mutants (L118T, L118A, L118I, and L118V) were successfully obtained. The best mutant, L118T, exhibited an improved thermal stability with a 3.7-fold enhancement in its half-life (t1/2) at 40 °C and a 5.3 °C increase in T5010 compared to the values for the wild-type protein. By the differential scanning fluorimetry (DSF) analysis, the best mutant, L118T, showed a melting temperature (Tm) of 46.4 °C, which corresponded to a 5.0 °C increase relative to the wild-type AT-ATA (41.4 °C). Furthermore, the most stable mutant L118T displayed the highest catalytic efficiency among the four stabilized mutants.

[Moxibustion Improves Learning Ability by Regulating Hippocampal Neurotrophic Factor Expression and Notch Signaling in Vascular Dementia Rats].

OBJECTIVE: To observe the effect of moxibustion on the learning ability and expression of neurotrophic factors and Notch signaling in vascular dementia (VD) rats, so as to explore its neurogenesis mechanism underlying improvement of VD. METHODS: Sixty SD rats were equally and randomly divided into sham operation (sham), model, medication and moxibustion groups (n=15 rats/group). The VD model was established by occlusion of the bilateral cervical common arteries and reperfusion. Moxibustion was applied to "Dazhui"(GV 14), "Guanyuan"(CV 4) and "Mingmen"(GV 4)for 15 minutes, once daily, 6 times a week for 4 weeks. Rats of the medication group were treated by gavage of nimodipine (2 mg·kg-1·d-1),3 times a day, 6 days a week for 4 weeks. Morris water maze tests were performed to detect the rat's learning-memory ability. The infarcted size of the brain was detected by using 2,3,5-triphenyltetrazolium chloride (TTC) staining, and H.E. staining was used to detect the histopathological changes. The expression level of glia fibrillary acidic protein (GFAP), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), Notch 1 (a receptor), Hes 3 (a downstream effector) mRNAs and proteins in the hippocampal tissues were detected by quantitative real-time PCR and Western blot, respectively. RESULTS: After 4 weeks' intervention, modeling-induced increase of escape latency was significantly shortened in both moxibustion and medication groups relevant to the model group (P<0.05), and the infarct size was reduced and the damage degree of nerve cells in the brain tissue alleviated. The expression levels of BDNF, NGF, GFAP, Hes 3, Notch 1 genes and proteins were significantly up-regulated in the model group relevant to the sham operation group (P<0.05,P<0.01). After the intervention, the expression levels of hippocampal BDNF, NGF, GFAP, Hes 3 and Notch 1 mRNAs and proteins in the moxibustion group, and NGF and GFAP mRNAs, and BDNF, NGF, GFAP, Hes 3 and Notch 1 proteins in the medication group were further obviously up-regulated relevant to the model group (P<0.05, P<0.01). The effect of moxibustion was significantly superior to that of medication in up-regulating GFAP, Hes 3, Notch 1 mRNAs expression (P<0.05,P<0.01). No significant differences were found in the expression of BDNF, Hes 3 and Notch 1 mRNAs in the medication group relevant to the model group (P<0.05), and between the moxibustion and medication groups in up-regulating the expression of BDNF and NGF mRNAs, and in up-regulating the expression of BDNF, NGF, GFAP, Hes 3 and Notch 1 proteins (P<0.05). CONCLUSIONS: Moxibustion can improve learning ability in VD rats, which may be associated with its effects in up-regulating the expression of neurotrophic factors and in potentiating Notch signaling.

Dramatic increases in blood glutamate concentrations are closely related to traumatic brain injury-induced acute lung injury.

Traumatic brain injury-induced acute lung injury (TBI-ALI) is a serious complication after brain injury for which predictive factors are lacking. In this study, we found significantly elevated blood glutamate concentrations in patients with TBI or multiple peripheral trauma (MPT), and patients with more severe injuries showed higher blood glutamate concentrations and longer durations of elevated levels. Although the increase in amplitude was similar between the two groups, the duration was longer in the patients with TBI. There were no significant differences in blood glutamate concentrations in the patients with MPT with regard to ALI status, but the blood glutamate levels were significantly higher in the patients with TBI-ALI than in those without ALI. Moreover, compared to patients without ALI, patients with TBI showed a clearly enhanced inflammatory response that was closely correlated with the blood glutamate levels. The blood glutamate concentration was also found to be a risk factor (adjusted odds ratio, 2.229; 95% CI, 1.082-2.634) and was a better predictor of TBI-ALI than the Glasgow Coma Scale (GCS) score. These results indicated that dramatically increased blood glutamate concentrations were closely related to the occurrence of TBI-ALI and could be used as a predictive marker for "at-risk" patients.