Synthesis of 2,4-Disubstituted Oxazoles and Thiazoles via Brønsted Acid-Catalyzed Cyclization of α-diazoketones with Amides.

A novel method is described for the synthesis of 2,4-disubstituted oxazole and thiazole derivates via the coupling of α-diazoketones with (thio)amides or thioureas using trifluoromethanesulfonic acid (TfOH) as a catalyst. This protocol is characterized by mild reaction conditions, metal-free, and simplicity and also features good functional group tolerance, good to excellent yields, and a broad substrate scope with more than 40 examples. Experimental studies suggest a mechanism involving 2-oxo-2-phenylethyl trifluoromethanesulfonate as the key intermediate.

APIPred: An XGBoost-Based Method for Predicting Aptamer-Protein Interactions.

Aptamers are single-stranded DNA or RNA oligos that can bind to a variety of targets with high specificity and selectivity and thus are widely used in the field of biosensing and disease therapies. Aptamers are generated by SELEX, which is a time-consuming procedure. In this study, using in silico and computational tools, we attempt to predict whether an aptamer can interact with a specific protein target. We present multiple data representations of protein and aptamer pairs and multiple machine-learning-based models to predict aptamer-protein interactions with a fair degree of selectivity. One of our models showed 96.5% accuracy and 97% precision, which are significantly better than those of the previously reported models. Additionally, we used molecular docking and SPR binding assays for two aptamers and the predicted targets as examples to exhibit the robustness of the APIPred algorithm. This reported model can be used for the high throughput screening of aptamer-protein pairs for targeting cancer and rapidly evolving viral epidemics.

Enantioselective Tsuji-Trost α-Fluoroallylation of Amino Acid Esters with Gem-Difluorinated Cyclopropanes.

A novel enantioselective Tsuji-Trost-type cross coupling reaction between gem-difluorinated cyclopropanes and N-unprotected amino acid esters enabled by synergistic Pd/Ni/chiral aldehyde catalysis is presented herein. This transformation streamlined the diversity-oriented synthesis (DOS) of optically active α-quaternary α-amino acid esters bearing a linear 2-fluoroallylic motif, which served as an appealing platform for the construction of other valuable enantioenriched compounds. The key intermediates were confirmed by HRMS detection, while DFT calculations revealed that the excellent enantioselectivity was attributed to the stabilizing non-covalent interactions between the Pd(II)-π-fluoroallyl species and the Ni(II)-Schiff base complex.

Characterization of benzylisoquinoline alkaloid methyltransferases in Liriodendron chinense provides insights into the phylogenic basis of angiosperm alkaloid diversity.

Benzylisoquinoline alkaloids (BIAs) are a class of plant secondary metabolites with great pharmacological value. Their biosynthetic pathways have been extensively elucidated in the species from the Ranunculales order, such as poppy and Coptis japonica, in which methylation events play central roles and are directly responsible for BIA chemodiversity. Here, we combined BIA quantitative profiling and transcriptomic analyses to identify novel BIA methyltransferases (MTs) from Liriodendron chinense, a basal angiosperm plant. We identified an N-methyltransferase (LcNMT1) and two O-methyltransferases (LcOMT1 and LcOMT3), and characterized their biochemical functions in vitro. LcNMT1 methylates (S)-coclaurine to produce mono- and dimethylated products. Mutagenesis experiments revealed that a single-residue alteration is sufficient to change its substrate selectivity. LcOMT1 methylates (S)-norcoclaurine at the C6 site and LcOMT3 methylates (S)-coclaurine at the C7 site, respectively. Two key residues of LcOMT3, A115 and T301, are identified as important contributors to its catalytic activity. Compared with Ranunculales-derived NMTs, Magnoliales-derived NMTs were less abundant and had narrower substrate specificity, indicating that NMT expansion has contributed substantially to BIA chemodiversity in angiosperms, particularly in Ranunculales species. In summary, we not only characterized three novel enzymes that could be useful in the biosynthetic production of valuable BIAs but also shed light on the molecular origin of BIAs during angiosperm evolution.

Horienoids A and B, Two Heterocoupled Sesquiterpenoid Dimers from Hedyosmum orientale.

Two eudesmane-guaiane/lindenane heterocoupled sesquiterpenoid dimers, horienoids A (1) and B (2) with new carbon skeletons, from Hedyosmum orientale were characterized by a combined method. Compound 1 featured a unique 2,10-dioxabicyclo[6.2.1]undecane core moiety with an anti-Bredt bridgehead double bond. Their biogenetic pathways were proposed to involve Diels-Alder and cascade rearrangement reactions as the key steps. Compound 2 exhibited a potent anti-inflammatory effect on LPS-induced BV-2 microglial cells.

Prevalence of Concomitant Coronary Artery Disease and Its Impact on Acute Kidney Injury for Chinese Adult Patients Undergoing Valvular Heart Surgery.

INTRODUCTION: Significant coronary artery disease (CAD) in patients undergoing valvular heart surgery (VHS) is an indication for combined valvular heart surgery and coronary artery bypass grafting. However, the impact of nonsignificant CAD on postoperative outcomes is not well understood. This study illustrated the epidemiological characteristics of CAD in China and investigated the impact of CAD on postoperative acute kidney injury (AKI), intensive care unit (ICU) stay, and postoperative mortality. METHODS: This study comprised an epidemiological survey followed by a case-control investigation. The epidemiological characteristics of CAD were studied in 4,172 consecutive patients who underwent coronary angiography before planned VHS at a core cardiovascular center. Then, 3,618 patients were selected for the subsequent case-control study to further analyze the associations between CAD and postoperative advanced AKI (grade 2 or 3 by KDIGO criteria), longer ICU stay (highest quartile), and increased mortality by logistic regression. RESULTS: Of the participants, 5.1 and 9.3% had moderate and significant CAD, respectively. The incidence of CAD increased after 60 years of age. Although CAD was not related to longer postoperative ICU stay in a multivariate logistic model, moderate CAD (OR 1.539 [95% CI 1.078-2.199]) and significant CAD (OR 1.798 [95% CI 1.094-2.955]) remained independent risk factors for postoperative advanced AKI after adjusting for multiple traditional risk factors. Significant CAD, but not nonsignificant CAD, was associated with postoperative mortality. CONCLUSIONS: Concomitant CAD is common in Chinese patients who undergo VHS. Moderate and significant CAD might have detrimental effects on postoperative advanced AKI.

A stoichiometric CdS interlayer for the photovoltaic performance enhancement of quantum-dot sensitized solar cells.

The CdS interlayer plays an important role as the seed layer and energy barrier in photovoltaic performance enhancement of CdSe quantum-dot sensitized solar cells (QDSCs). However, the CdS (CdS-CBD) interlayer is generally synthesized by the chemical bath deposition method (CBD) and suffers from excessive Cd2+ due to the poor controllability of interfacial chemical reactions. Here, we employed a sol-gel method to prepare a CdS interlayer (CdS-SG) with a stoichiometric ratio of Cd2+ to S2- on a TiO2 mesoporous photoanode and then fabricated CdSe QDSCs. A power conversion efficiency of 3.37% was obtained in the CdS-SG QDSCs (Cell-SG), which is higher than that of 2.64% in the CdS-CBD QDSCs (Cell-CBD) under AM 1.5G solar illumination of 100 mW cm-2. Charge extraction measurements showed that the Cell-SG contained fewer trap states than the Cell-CBD. A comprehensive study of the electron dynamics based on open-circuit voltage decay (OCVD), electrochemical impedance spectroscopy (EIS), intensity-modulated voltage spectroscopy (IMVS), and intensity-modulated photocurrent spectroscopy (IMPS) measurements revealed that the stoichiometric CdS-SG interlayer significantly reduced the charge recombination and prolonged the lifetime of photogenerated electrons in contrast to the CdS-CBD interlayer in the QDSCs.

Euphorhelipanes A and B, Triglyceride-Lowering Euphorbia Diterpenoids with a Bicyclo[4.3.0]nonane Core from Euphorbia helioscopia.

Euphorhelipanes A (1) and B (2), two Euphorbia diterpenoids with a new 4-(5,5-dimethylheptan-2-yl)-2,7-dimethylbicyclo[4.3.0]nonane skeleton, were isolated from a 95% ethanol extract of the whole plants of Euphorbia helioscopia. Their structures were elucidated by spectroscopic data analysis, quantum chemical calculations, and single-crystal X-ray diffraction data. Compounds 1 and 2 represent the first examples of Euphorbia diterpenoids with a 5/6 fused carbon ring system, and their plausible biosynthetic pathways originating from jatrophanes are proposed. Compounds 1 and 2 showed a triglyceride-lowering effect in oleic-acid-stimulated HuH7 cells at concentrations of 1-50 µM.

High hemoglobin is associated with increased in-hospital death in patients with chronic obstructive pulmonary disease and chronic kidney disease: a retrospective multicenter population-based study.

BACKGROUND: Chronic kidney disease (CKD) is a common comorbidity of chronic obstructive pulmonary disease (COPD). Although high hemoglobin (Hb) is detrimental to CKD patients, its relationship with poor outcomes in the COPD population has not been reported. This study aimed to investigate the relationship between high Hb and in-hospital mortality and to explore reference Hb intervals in patients with COPD and CKD. METHODS: This retrospective study was multicenter population-based. A total of 47,209 patients who presented with COPD between January 2012 and December 2016 were included. The average Hb level during hospitalization was used as the Hb level. CKD and advanced CKD were defined as estimated glomerular filtration rates < 60 and < 30 ml/min/1.73 m2, respectively. The association between Hb level (measured in 1 g/dL intervals) and in-hospital mortality was analyzed in different multivariable logistic regression models by CKD stratification. RESULTS: The Hb level was decreased in the CKD subgroup. In the non-CKD group, a higher Hb level was not associated with an increased risk of in-hospital death. However, the Hb level and mortality showed a U-shaped relationship in the CKD group. After adjusting for age and Charlson Comorbidity Index, multivariable regression analysis showed that an Hb level > 17 g/dL was associated with an increased risk of death in the CKD group with an odds ratio (OR) of 2.085 (95% CI, 1.019-4.264). Hb > 14 g/dL was related to an increased risk of death in advanced CKD patients (OR, 4.579 (95% CI, 1.243-16.866)). CONCLUSIONS: High Hb is associated with an increased risk of in-hospital death in COPD patients with CKD, especially among those with advanced CKD. In this group of patients, attention should be paid to those with high Hb levels.

Comparative Study of Choke Vessel Reconstruction With Single and Multiple Perforator-Based Flaps on the Murine Back Using Delayed Surgery.

OBJECTIVE: Choke vessels, vascular anastomosis between adjacent angiosome, play an important role in flap expansion and survival. Here we established a flap model with single and multiple perforators to detect and compare the changes in choke vessels, discuss the effect of hemodynamics on the vascular morphology, and explore the underlying mechanism. METHODS: One hundred mice (7-8 weeks) were subjected to a "choke zone" surrounded by 4 perforators on their backs. Delayed surgery was performed by the ligation of 1, 2, or 3 perforators to establish flap models. The blood flow of the choke zone was measured by laser Doppler flowmetry preoperatively and 6 hours and 1, 3, 5, and 7 days. The morphological changes of choke vessels in the choke zone were observed by gross and histological analyses. Levels of angiogenesis-related markers such as endothelial nitric oxide synthase (eNOS), metalloproteinase 2, hypoxia-inducible factor 1α (HIF-1α), and intercellular adhesion molecule 2 (ICAM-2) were detected by Western blotting and enzyme-linked immunosorbent assay. RESULTS: Blood flow and microvascular count were obviously increased postoperatively and peaked and were maintained for 1 week (P < 0.01). Meanwhile, the diameters of the choke vessels expanded. The eNOS level was increased at 7 days (P < 0.05); however, the enzyme-linked immunosorbent assay results showed that the HIF-1α and ICAM-2 levels were decreased at 7 days. CONCLUSIONS: (1) The delayed surgery that kept a single perforator had the greatest impact on the choke zone. (2) Changes in choke vessels were closely related to the shear stress caused by enhanced blood perfusion after surgery. (3) Choke vessel growth was regulated by eNOS, metalloproteinase 2, HIF-1α, and ICAM-2.

Colocynthenins A-D, Ring-A seco-Cucurbitane Triterpenoids from the Fruits of Citrullus colocynthis.

Four ring-A seco-cucurbitane triterpenoids, colocynthenins A-D (1-4), together with seven known cucurbitane triterpenoids (5-11), were isolated from the fruits of Citrullus colocynthis. Their structures and absolute configurations were elucidated based on spectroscopic analysis and quantum chemical ECD calculations. Compound 1 possesses an unprecedented 2,11-lactone moiety, while compound 2 is the first reported cucurbitane triterpenoid with an unusual cyano group. Compounds 1 and 3 showed acetylcholinesterase inhibitory activities in a standard in vitro assay, with IC50 values of 2.6 and 3.1 µM, respectively.

[The correlation of vitamin D level and vitamin D-binding protein gene polymorphism in chronic obstructive pulmonary disease].

OBJECTIVE: To assess the correlation of serum 25-hydroxyvitamin D (25-OHD) levels with vitamin D-binding protein (the group-specific component, GC) gene polymorphism in chronic obstructive pulmonary disease (COPD). METHODS: In a cross-sectional case-control study, 250 participants, including 116 COPD patients with smoking history and 134 healthy smokers, were investigated. A questionnaire about smoking history, vitamin D intake and comorbidities was collected. General pulmonary function was done by routine. Serum 25-OHD levels were detected by ELISA. The genetic variants (rs4588 and rs7041) were genotyped by real time fluorescence polymerase chain reaction (RT-PCR) with TaqMan probe technology. RESULTS: The COPD patients had lower serum vitamin D level than the smoker subjects (36.58 nmol/L vs 43.80 nmol/L, P < 0.001). In the COPD patients, vitamin D level was 39.43 nmol/L in those with percentage of predicted forced expiratory volume in 1 second (FEV1%pred) greater than or equal to 80%.In other groups with FEV1%pred 50%-80%, 30%-50% and lower than 30%, vitamin D levels were 35.32 nmol/L, 32.21 nmol/L, 26.25 nmol/L respectively (P < 0.01). Moreover, there was a significant relevance of 25-OHD levels with FEV1%pred in both COPD patients and healthy smokers (r(2) = 1.911; P < 0.000 1). The mean 25-OHD concentration had a negative correlation with Global Initiative for Obstructive Lung Disease (GOLD) stages. Homozygous carriers of vitamin D-binding protein gene rs7041 T allele were independently related to 25-OHD levels and susceptibility of COPD (P < 0.01; OR = 2.140, 95%CI 1.157-3.959, P = 0.015 respectively). CONCLUSIONS: Patients with COPD are at high risk of vitamin D deficiency and the severity of COPD is inversely correlated with vitamin D levels. Furthermore, homozygous carrier of rs7041 T allele influences 25-OHD serum levels and is related to susceptibility of COPD, which may be a potential candidate gene for screening COPD.

Multiple influence of immune cells in the bone metastatic cancer microenvironment on tumors.

Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high relapse rate. Immune and bone cells in situ constitute a unique immune microenvironment, which plays a crucial role in the context of bone metastasis. This review firstly focuses on lymphatic cells in bone metastatic cancer, including their function in tumor dissemination, invasion, growth and possible cytotoxicity-induced eradication. Subsequently, we examine myeloid cells, namely macrophages, myeloid-derived suppressor cells, dendritic cells, and megakaryocytes, evaluating their interaction with cytotoxic T lymphocytes and contribution to bone metastasis. As important components of skeletal tissue, osteoclasts and osteoblasts derived from bone marrow stromal cells, engaging in 'vicious cycle' accelerate osteolytic bone metastasis. We also explain the concept tumor dormancy and investigate underlying role of immune microenvironment on it. Additionally, a thorough review of emerging treatments for bone metastatic malignancy in clinical research, especially immunotherapy, is presented, indicating current challenges and opportunities in research and development of bone metastasis therapies.

Cancer cells reprogram to metastatic state through the acquisition of platelet mitochondria.

Metastasis is the major cause of cancer deaths, and cancer cells evolve to adapt to various tumor microenvironments, which hinders the treatment of tumor metastasis. Platelets play critical roles in tumor development, especially during metastasis. Here, we elucidate the role of platelet mitochondria in tumor metastasis. Cancer cells are reprogrammed to a metastatic state through the acquisition of platelet mitochondria via the PINK1/Parkin-Mfn2 pathway. Furthermore, platelet mitochondria regulate the GSH/GSSG ratio and reactive oxygen species (ROS) in cancer cells to promote lung metastasis of osteosarcoma. Impairing platelet mitochondrial function has proven to be an efficient approach to impair metastasis, providing a direction for osteosarcoma therapy. Our findings demonstrate mitochondrial transfer between platelets and cancer cells and suggest a role for platelet mitochondria in tumor metastasis.

[The expression of macrophage migration inhibition factor in pulmonary tissues of smokers with or without chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the expression of macrophage migration inhibition factor (MIF) in pulmonary tissues of the smokers with and without chronic obstructive pulmonary disease (COPD). METHODS: The subjects were assigned into three groups: non-smokers without COPD (control group, n = 12), smokers without COPD (smoker group, n = 13) and smokers with COPD (COPD group, n = 16). The specimens were obtained from lung tissues as far away from cancer focus as possible (> 5 cm). Real-time quantitative PCR and immunohistochemistry were used to investigate the expression and distribution of MIF in pulmonary tissues. The relationship between the severity of airflow obstruction and the differential expressions of MIF in lung tissues of the smokers with or without COPD was analyzed. RESULTS: (1) MIF mRNA expression in COPD group (4.87 ± 1.79) was higher than that in the smoker group (2.16 ± 0.72; P < 0.01), which was higher than that in the control group (1.09 ± 0.48; P < 0.01). (2) Immunohistochemistry analysis showed that MIF protein expression in lung tissues of the COPD group (0.277 ± 0.025) was higher than that in the smokers group (0.199 ± 0.034; P < 0.01), which was significantly higher than that in control group (0.130 ± 0.021; P < 0.01). (3) Correlation analysis of MIF mRNA expression in the lung tissues and pulmonary function parameters of forced expired volume in one second (FEV(1)) percentage of predicted (FEV(1) pred)and ratio of FEV(1) to forced vital capacity (FEV(1)/FVC) suggested that MIF mRNA expression in the lung tissues was negatively related with FEV(1) pred (r = -0.578, P < 0.01) and FEV(1)/FVC (r = -0.607, P < 0.01). CONCLUSIONS: MIF expression significantly increases in the smokers with COPD, and MIF level in the lung is positively correlated with airflow limitation. The results suggest that MIF may play an important role in the pathogenesis of smoking-induced COPD.

[Expression of ß-catenin in human pulmonary tissues of smokers with and without chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the expression of ß-catenin in pulmonary tissues of smokers with and without chronic obstructive pulmonary disease (COPD). METHODS: Pulmonary tissues were obtained from patients who had underwent pneumonectomy in Tongji Hospital. The subjects were assigned into non-smokers without COPD (control group), smokers without COPD (smoker group) and smokers with COPD (smoker + COPD group) based on their pulmonary functions and smoking history, with 12 subjects each group. The specimens were obtained as far from the tumor focus (> 5 cm) as possible. Immunofluorescence staining, Western blot and real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) were used to investigate the expression and localization of ß-catenin in pulmonary tissues. Numerical data were expressed as the mean ± standard deviation, and were assessed for significance by one-way analysis of variance followed by a Student-Newman-Keuls test for multiple comparisons. The difference of enumeration data was detected by Chi-Square test. Relationship was estimated by Pearson correlation. RESULTS: Immunofluorescence analysis revealed that ß-catenin mainly expressed in the cell membrane of epithelial cells. There was also a positive expression in the cytoplasm and the nuclei of the epithelial cells. The number of alveolar epithelial cells with ß-catenin expressed in the cytoplasm and(or) nucleus was (1.2 ± 0.6)/HP in smokers + COPD group. And the protein and mRNA expression of ß-catenin in pulmonary tissues in smokers + COPD group were 0.26 ± 0.11 and 0.351 ± 0.129, respectively, which were significantly less than those of the smoker group and the control group [(5.0 ± 2.5)/HP and (8.4 ± 3.5)/HP, 0.62 ± 0.23 and 1.00 ± 0.50, 0.60 ± 0.14 and 1.03 ± 0.27]. The differences among the 3 groups were significant (F = 12.809 - 38.776, P < 0.05). Correlation analysis between ß-catenin expression and pulmonary function suggested that the protein and mRNA expression of ß-catenin positively related with FEV(1)%pred (P < 0.05) and FEV(1)/FVC (r = 0.402 - 0.558, P < 0.05). CONCLUSION: ß-catenin expression significantly was decreased in smokers with COPD, and ß-catenin level in the lungs was positively correlated with pulmonary function.

Anti-CRISPRdb v2.2: an online repository of anti-CRISPR proteins including information on inhibitory mechanisms, activities and neighbors of curated anti-CRISPR proteins.

We previously released the Anti-CRISPRdb database hosting anti-CRISPR proteins (Acrs) and associated information. Since then, the number of known Acr families, types, structures and inhibitory activities has accumulated over time, and Acr neighbors can be used as a candidate pool for screening Acrs in further studies. Therefore, we here updated the database to include the new available information. Our newly updated database shows several improvements: (i) it comprises more entries and families because it includes both Acrs reported in the most recent literatures and Acrs obtained via performing homologous alignment; (ii) the prediction of Acr neighbors is integrated into Anti-CRISPRdb v2.2, and users can identify novel Acrs from these candidates; and (iii) this version includes experimental information on the inhibitory strength and stage for Acr-Cas/Acr-CRISPR pairs, motivating the development of tools for predicting specific inhibitory abilities. Additionally, a parameter, the rank of codon usage bias (CUBRank), was proposed and provided in the new version, which showed a positive relationship with predicted result from AcRanker; hence, it can be used as an indicator for proteins to be Acrs. CUBRank can be used to estimate the possibility of genes occurring within genome island-a hotspot hosting potential genes encoding Acrs. Based on CUBRank and Anti-CRISPRdb, we also gave the first glimpse for the emergence of Acr genes (acrs). DATABASE URL: http://guolab.whu.edu.cn/anti-CRISPRdb.

Quantitative regression analysis of the cutaneous vascular territories in a rat model.

BACKGROUND: The rat skin flap model has been widely used in experimental flap survival studies; however, most of these have been qualitative studies. The purpose of this study was to investigate the quantitative relationship between the diameter of a cutaneous artery and the area of skin that it supplies, and also to explore the factors that influence this relationship. METHODS: Thirty rats were injected with lead oxide and gelatin and then radiographed. Computer imaging of the diameter and the area of blood supply of the cutaneous artery were made to investigate the mathematical relationship between the arterial diameter and its perfusion area. Angiograms were assembled using Adobe Photoshop and analyzed with Scion Image and SPSS software. RESULTS: The blood vessels had an average diameter of 0.53 ± 0.12 mm, perimeter of 18.74 ± 4.84 cm, vascular density of 391.31 ± 76.58 gray value/pixel cm, vascular territory of 22.32 ± 10.04 cm(2) and supplying volume of 4.88 ± 3.02 cm(3). There was a positive correlation between the diameter and the perimeter of the vascular territory, and the area and volume of the vascular territory. The linear regression equation was y = 32.44x + 1.23 [y: nutrition region perimeter (cm), x: cutaneous artery diameter (mm)], y = 72.70x-15.93 [y: supplying area (cm(2)), x: cutaneous artery diameter (mm)] and y = 20.36x-5.83 [y: supplying volume (cm(3)), x: cutaneous artery diameter (mm)], respectively. CONCLUSIONS: Based on this data, it is postulated that the size of reliable skin flaps can be calculated by the diameter and the distribution patterns of the cutaneous artery. With the same diameter, the area of the flap supplied by branch-style artery is larger than the one supplied by the axial artery.

[Effect of electroacupuncture on nitric oxide synthase in rats with cerebral ischemia-reperfusion injury].

OBJECTIVE: To study the effect of electroacupuncture on nitric oxide synthase (NOS) in rats with cerebral ischemia-reperfusion injury. METHODS: Focal cerebral ischemia-reperfusion model was established using modified intravascular suture technique. The NO content in the brain tissue was detected by nitrite reduction and the expressions of nNOS and iNOS were detected by immunohistochemistry. Eighty rats in this experiment were divided into the normal group, the cerebral ischemia-reperfusion injury model group (as the model group), the cerebral ischemia-reperfusion injury + electroacupuncture group (as the acupuncture group), and the cerebral ischemia-reperfusion injury + phosphatidylinositol 3 kinase (PI3-K) inhibitor group (as the inhibitor group). Each group consisted of twenty rats. Five microL PI3-K inhibitor LY294002 (400 microL) was slowly injected at the lateral cerebral ventricle of rats in the inhibitor group at a constant speed using microinjector according to Konig Klippel atlas of the stereotaxis instrument. Shuigou (DU26) and Chengjiang (RN24) were selected to determine levels of NO and NOS. RESULTS: After 24-h ischemia-reperfusion, the NO levels of the hippocampus and the cerebral cortex increased abnormally, and the expressions of nNOS and iNOS increased, showing significant difference when compared with those of the normal group (P<0.05). By electroacupuncture at Shuigou (DU26) and Chengjiang (RN24), the ischemic cerebral ischemia-reperfusion injury neuron loss was inhibited. Meanwhile, the high levels of NO, nNOS and iNOS in the cerebral cortex and the hippocampus were significantly inhibited (P<0.05). The abnormally increased expressions of nNOS and iNOS were reversed, showing significant difference when compared with the model group (P<0.05). But when compared with the normal group, there was no significant difference (P>0.05). The effects of electroacupuncture reversed the abnormally increased NO levels of the hippocampus and the cerebral cortex and expressions of nNOS and iNOS after LY294002 oppressed anti-PI3K to block the TrkA acceptor circuit. The NO levels of the hippocampus and the cerebral cortex and expressions of nNOS and iNOS increased again, showing significant difference when compared with the acupuncture group (P<0.05). CONCLUSIONS: Acupuncture fought against cerebral ischemia and reperfusion in the loss of neurons, at the same time, the abnormal regulation of NOS had reverse effect partly through TrkA/PI3K mediated signal transduction pathway.

Deep Fractional Max Pooling Neural Network for COVID-19 Recognition.

Aim: Coronavirus disease 2019 (COVID-19) is a form of disease triggered by a new strain of coronavirus. This paper proposes a novel model termed "deep fractional max pooling neural network (DFMPNN)" to diagnose COVID-19 more efficiently. Methods: This 12-layer DFMPNN replaces max pooling (MP) and average pooling (AP) in ordinary neural networks with the help of a novel pooling method called "fractional max-pooling" (FMP). In addition, multiple-way data augmentation (DA) is employed to reduce overfitting. Model averaging (MA) is used to reduce randomness. Results: We ran our algorithm on a four-category dataset that contained COVID-19, community-acquired pneumonia, secondary pulmonary tuberculosis (SPT), and healthy control (HC). The 10 runs on the test set show that the micro-averaged F1 (MAF) score of our DFMPNN is 95.88%. Discussions: This proposed DFMPNN is superior to 10 state-of-the-art models. Besides, FMP outperforms traditional MP, AP, and L2-norm pooling (L2P).