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Hua-Man Wu,1,2,* Zhi-Jun Wang,1,* Chao-Hong Cheng,1 Tong Su,1 Jing Wang,1 Ye-Zhou Li,3 Qiao-Jun Wang,4 Fei Han,4 Rui Chen1,4 1Department of Respiratory, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Zigong First People’s Hospital, Zigong, Sichuan, People’s Republic of China; 3School of Medicine, the University of Manchester, Manchester, UK; 4Department of Sleeping Center, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rui Chen, Department of Respiratory/Department of Sleeping Center, the Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, People’s Republic of China, Tel +86(0512)67784857, Email chenruigood@126.comPurpose: Obstructive sleep apnea hypopnea syndrome (OSAHS) can lead to cognitive impairment, though few studies have so far examined hypercapnia as its causal mechanism, due to the invasive nature of conventional arterial CO2 measurement. The study aims to investigate the effects of daytime hypercapnia on working memory in young and middle-aged patients with OSAHS.Patients and Methods: This prospective study screened 218 patients and eventually recruited 131 patients (aged 25– 60 years) with polysomnography (PSG)-diagnosed OSAHS. Using a cut-off of 45mmHg daytime transcutaneous partial pressure of carbon dioxide (PtcCO2), 86 patients were assigned into the normocapnic group and 45 patients into the hypercapnic group. Working memory was evaluated using the Digit Span Backward Test (DSB) and the Cambridge Neuropsychological Test Automated Battery.Results: Compared with the normocapnic group, the hypercapnic group performed worse in verbal, visual, and spatial working memory tasks. PtcCO2≥ 45mmHg was an independent predictor for lower DSB scores (OR=4.057), lower accuracy in the immediate Pattern Recognition Memory (OR=2.600), delayed Pattern Recognition Memory (OR=2.766) and Spatial Recognition Memory (OR=2.722) tasks, lower Spatial Span scores (OR=4.795), and more between errors in the Spatial Working Memory task (OR=2.734 and 2.558, respectively). Notably, PSG indicators of hypoxia and sleep fragmentation did not predict task performance.Conclusion: Hypercapnia may be plays an important role in working memory impairment in patients with OSAHS, perhaps more so than hypoxia and sleep fragmentation. Routine CO2 monitoring in these patients could prove of utility in clinical practices.Keywords: hypercapnia, obstructive, sleep apnea, working memory

The Bcl-2 antagonist ABT-737 targets Bcl-2/Bcl-xL, but not Mcl-1, which may confer resistance to this agent in various cancers with high levels of Mcl-1. Here, we showed that the combination of gemcitabine and ABT-737 exhibited synergistic cytotoxicity and induced significant apoptosis in multiple cancer types, including lung, renal, bladder, and prostate cancers. The enhanced apoptosis induced by gemcitabine plus ABT-737 was accompanied by the greater extent of mitochondrial depolarization, caspases-3 activation, and PARP cleavage in 95-D and 5637 cell lines. Importantly, in ABT-737–resistant cancer cells, the interaction between USP9X and Mcl-1, which was increased by ABT-737 treatment, could be disrupted by gemcitabine, thus resulting in enhanced ubiquitination and the subsequent degradation of Mcl-1 and ultimately in the synergism of these two drugs. Moreover, the increased anticancer efficacy of gemcitabine combined with ABT-737 was further validated in a human lung cancer 95-D xenograft model in nude mice. Taken together, our data first showed the synergistic anticancer capabilities achieved by combining gemcitabine and ABT-737 and, second, opened new opportunities to use antiapoptotic Bcl-2 family members, which drive tumor cell resistance in current anticancer therapies, therapeutically. Mol Cancer Ther; 10(7); 1264–75. ©2011 AACR.

PDF file - 135K, Supplementary Table S1. CI Values of SN-38 at Concentrations Applied in Combination with Tirapazamine in Different Liver Cell Lines; Supplementary Table S2. In Vivo Efficacy of CPT-11 in Combination with Tirapazamine; and supplementary figure legends.

Supplementary Methods, Figures 1-3 from Synergistic Antitumor Activity of Gemcitabine and ABT-737 In Vitro and In Vivo through Disrupting the Interaction of USP9X and Mcl-1

PDF file - 131K, Figure S4. TPZ and SN-38 decrease the rate of HIF-1alpha protein synthesis.

PDF file - 89K, Figure S6. Overexpression of HIF-1α could weaken the synergistic effect of SN-38 and TPZ.

Hepatocellular carcinoma is among the leading causes of cancer-related deaths worldwide, and the development of new treatment regimens is urgently needed to improve therapeutic approach. In our study, we found that the combination of a Met inhibitor, cabozantinib, and a novel FAK inhibitor, CT-707, exerted synergistic antitumor effects against hepatocellular carcinoma in vitro and in vivo. Interestingly, further studies showed that therapeutic concentrations of cabozantinib increased the phosphorylation of FAK, which might attenuate the antitumor activity of cabozantinib. The simultaneous exposure to CT-707 effectively inhibited the activation of FAK that was induced by cabozantinib, which contributes to the synergistic effect of the combination. Furthermore, cabozantinib increased the mRNA and protein levels of integrin α5, which is a canonical upstream of FAK, and the introduction of cilengitide to block integrin function could abrogate FAK activation by cabozantinib, indicating that cabozantinib upregulated the phosphorylation of FAK in an integrin-dependent manner. Similar synergy was also observed on PHA-665752, another selective MET inhibitor, indicating that this observation might be a common characteristic of MET-targeting strategies. Our findings not only favor the development of the novel FAK inhibitor CT-707 as a therapeutic agent against hepatocellular carcinoma but also provide a new strategy of combining MET and FAK inhibitors to potentiate the anticancer activities of these two types of agents for treating hepatocellular carcinoma patients. Mol Cancer Ther; 15(12); 2916–25. ©2016 AACR.

Topoisomerase I inhibitors are a class of anticancer drugs with a broad spectrum of clinical activity. However, they have limited efficacy in hepatocellular cancer. Here, we present in vitro and in vivo evidence that the extremely high level of hypoxia-inducible factor-1α (HIF-1α) in hepatocellular carcinoma is intimately correlated with resistance to topoisomerase I inhibitors. In a previous study conducted by our group, we found that tirapazamine could downregulate HIF-1α expression by decreasing HIF-1α protein synthesis. Therefore, we hypothesized that combining tirapazamine with topoisomerase I inhibitors may overcome the chemoresistance. In this study, we investigated that in combination with tirapazamine, topoisomerase I inhibitors exhibited synergistic cytotoxicity and induced significant apoptosis in several hepatocellular carcinoma cell lines. The enhanced apoptosis induced by tirapazamine plus SN-38 (the active metabolite of irinotecan) was accompanied by increased mitochondrial depolarization and caspase pathway activation. The combination treatment dramatically inhibited the accumulation of HIF-1α protein, decreased the HIF-1α transcriptional activation, and impaired the phosphorylation of proteins involved in the homologous recombination repair pathway, ultimately resulting in the synergism of these two drugs. Moreover, the increased anticancer efficacy of tirapazamine combined with irinotecan was further validated in a human liver cancer Bel-7402 xenograft mouse model. Taken together, our data show for the first time that HIF-1α is strongly correlated with resistance to topoisomerase I inhibitors in hepatocellular carcinoma. These results suggest that HIF-1α is a promising target and provide a rationale for clinical trials investigating the efficacy of the combination of topoisomerase I inhibitors and tirapazamine in hepatocellular cancers. Mol Cancer Ther; 13(3); 630–42. ©2013 AACR.

PDF file - 166K, Figure S2. TPZ enhanced the cytotoxicity elicited by several topoisomerase I inhibitors in Bel-7402 cells under hypoxia.

PDF file - 159K, Figure S1. Depletion of HIF-1alpha could reverse hypoxia-induced resistance to topoisomerase I inhibitors.

PDF file - 59K, Figure S5. Overexpression of HIF-1alpha is associated with resistance to topoisomerase I inhibitors in HCC cells.

The combination of cabozantinib and CT-707 imposed minimal synergistic cytotoxicity against the human hepatocyte HL-7702 cells.

PDF file - 293K, Figure S3. TPZ enhanced the cytotoxicity elicited by topoisomerase I inhibitors under hypoxia.

Introduction Fasciola hepatica is a trematode infecting ruminants worldwide and occasionally affecting other animal species, including humans. It causes significant economic losses. Geographic distribution and patterns of infection must be considered before control and management measures are developed for this parasite. DNA molecular markers are useful for the identification of flukes and elucidation of their genetic evolution. Therefore, the population structure of F. hepatica was studied using this method in sheep in Xinjiang, China. Material and Methods The molecular characteristics, genetic relationships within the population and dispersal patterns of F. hepatica isolates were analysed based on the cox1 and nad1 genes. The population structure of F. hepatica from three regions of Xinjiang was explored and a neutrality test was conducted. Results The cox1 and nad1 genes have 21 and 42 variable sites, respectively, which can be classified into 34 and 33 haplotypes. Median-joining network and phylogenetic tree analyses showed that there was no significant variation in F. hepatica isolates between the three geographical regions. Analysis of variance revealed that the genetic variation of F. hepatica was mainly present within the populations. The neutrality test indicated that the populations were relatively stable but the Hami population may have undergone short-term expansion. Conclusion This study revealed for the first time the molecular characteristics, genetic diversity and dispersal patterns of F. hepatica isolates from sheep in Xinjiang, thus providing new insights into the genetic variation and haplotype diversity of F. hepatica from indigenous sheep.

Si-Yi Gong,1,&ast; Yun Shen,1,&ast; Han-Ying Gu,1 Sheng Zhuang,1 Xiang Fu,1,2 Qiao-Jun Wang,1 Cheng-Jie Mao,1 Hua Hu,1 Yong-Ping Dai,1 Chun-Feng Liu1– 3 1Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 3Department of Neurology, Suqian First Hospital, Suqian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun-Feng Liu; Yong-Ping Dai, Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Tel +86 512-67783307 ; +86 512-67784179, Fax +86 512-68284303, Email liuchunfeng@suda.edu.cn; dai_yongping@163.comPurpose: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is the prodromal marker of α-synuclein degeneration with markedly high predictive value. We aim to evaluate the value of electroencephalography (EEG) data during rapid eye movement (REM) sleep and subjective RBD severity in predicting the conversion to neurodegenerative diseases in iRBD patients.Methods: At the baseline, iRBD patients underwent clinical assessment and video-polysomnography (PSG). Relative spectral power for nine frequency bands during phasic and tonic REM sleep in three regions of interest, slow-to-fast ratios, clinical and PSG variables were estimated and compared between iRBD patients who converted to neurodegenerative diseases (iRBD-C) and iRBD patients who remained disease-free (iRBD-NC). Receiver operating characteristic (ROC) curves evaluated the predictive performance of slow-to-fast ratios, and subjective RBD severity as assessed with RBD Questionnaire-Hong Kong.Results: Twenty-two (33.8%) patients eventually developed neurodegenerative diseases. The iRBD-C group showed shorter total sleep time (p < 0.001), lower stage 2 sleep percentage (p = 0.044), more periodic leg-movement-related arousal index (p = 0.004), increased tonic chin electromyelographic activity (p = 0.040) and higher REM density in the third REM episode (p = 0.034) than the iRBD-NC group. EEG spectral power analyses revealed that iRBD phenoconverters showed significantly higher delta and lower alpha power, especially in central and occipital regions during the phasic REM state compared to the iRBD-NC group. Significantly higher slow-to-fast ratios were observed in a more generalized way during the phasic state in the iRBD-C group compared to the iRBD-NC group. ROC analyses of the slowing ratio in occipital areas during phasic REM sleep yielded an area under the curve of 0.749 (p = 0.001), while no significant predictive value of subjective RBD severity was observed.Conclusion: Our study shows that EEG slowing, especially in a more generalized manner during the phasic period, may be a promising marker in predicting phenoconversion in iRBD, rather than subjective RBD severity.Keywords: idiopathic rapid eye movement sleep behavior disorder, neurodegenerative diseases, EEG slowing, RBD severity, phenoconversion, neuroprotective therapy

Cyclic guanosine monophosphate-adenosine monophosphate adenosine synthetase (cGAS) is a DNA sensor that detects and binds to cytosolic DNA to generate cyclic GMP-AMP (cGAMP). As a second messenger, cGAMP mainly activates the adapter protein STING, which induces the production of type I interferons (IFNs) and inflammatory cytokines. Mounting evidence shows that cGAS is extensively involved in the innate immune response, senescence, and tumor immunity, thereby exhibiting a tumor-suppressive function, most of which is mediated by the STING pathway. In contrast, cGAS can also act as an oncogenic factor, mostly by increasing genomic instability through inhibitory effects on DNA repair, suggesting its utility as an antitumor target. This article reviews the roles and the underlying mechanisms of cGAS in cancer, particularly focusing on its dual roles in carcinogenesis and tumor progression, which are probably attributable to its classical and nonclassical functions, as well as approaches targeting cGAS for cancer therapy.

Macrophages play a critical role in the pathogenesis of acetaminophen (APAP)-induced liver injury (AILI), a major cause of acute liver failure or even death. Sapidolide A (SA) is a sesquiterpene lactone extracted from Baccaurea ramiflora Lour., a folk medicine used in China to treat inflammatory diseases. In this study, we investigated whether SA exerted protective effects on macrophages, thus alleviated the secondary hepatocyte damage in an AILI. We showed that SA (5-20 μM) suppressed the phosphorylated activation of NF-κB in a dose-dependent manner, thereby inhibiting the expression and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and pyroptosis in LPS/ATP-treated mouse bone marrow-derived primary macrophages (BMDMs). In human hepatic cell line L02 co-cultured with BMDMs, SA (10 μM) protected macrophages from the pyroptosis induced by APAP-damaged L02 cells. Moreover, SA treatment reduced the secondary liver cell damage aggravated by the conditioned medium (CM) taken from LPS/ATP-treated macrophages. The in vivo assessments conducted on mice pretreated with SA (25, 50 mg/kg, ip) then with a single dose of APAP (400 mg/kg, ip) showed that SA significantly alleviated inflammatory responses of AILI by inhibiting the expression and activation of the NLRP3 inflammasome. In general, the results reported herein revealed that SA exerts anti-inflammatory effects by regulating NLRP3 inflammasome activation in macrophages, which suggests that SA has great a potential for use in the treatment of AILI patients.

We reveal the mechanism through which electron-deficient p states enhance the photocatalytic properties of g-C3N4 for CO2 reduction.

Background Image-defined risk factors (IDRF) in neuroblastoma have been developed to predict tumor resectability and surgical complications; however, the potential prognostic value of IDRF in neuroblastoma has been variably reported. Previous studies did not report the IDRF status separately from the International Neuroblastoma Risk Group (INRG) stage. Moreover, the association between IDRF and clinical and pathological factors has not been discussed further. Methods In this retrospective study, we investigated the clinical and biological features of neuroblastoma at different INRG stages based on IDRF. Event-free survival (EFS) and overall survival (OS) related to the INRG stage were analyzed using log-rank tests, and the prognostic value of the IDRF number and type was also evaluated. Results Among 72 patients, 182 IDRF at diagnosis were found in 79.2%. The distribution of the INRG stages was 10 L1 (13.9.0%), 25 L2 (34.7%), and 37 M/MS (51.4%). Patients with stage M/Ms had a larger tumor volume, a higher percentage of age ≥ 18 months, elevated lactate dehydrogenase (LDH) level, elevated ferritin level, and a higher percentage of COG high-risk compared with stage L1 and L2 patients. EFS and OS were similar for stage L1 and L2 tumors but were significantly poorer for metastatic disease. However, EFS (P = 0.06) and OS (P = 0.07) were similar for IDRF-negative and positive neuroblastomas. Patients with stage M/Ms with IDRF-positive had poorer EFS (P = 0.001) and OS (P

Additional file 21: Figure S5. RT–PCR amplification of 10 randomly selected ARG. M is the size marker (Takara DL500: 500 bp, 400 bp, 300 bp, 200 bp, 150 bp, 100 bp, and 50 bp), and N is the negative control.

Additional file 6: Figure S2. Assessment of the degree of contamination and integrity of 2272 high-quality MAG in the horse gut. The grey circles indicate 80–90% genome integrity with 5–10% contamination; the red circles indicate > 90% genome integrity with < 5% contamination.

Additional file 4: Figure S1. Rarefaction curve of the gene numbers in our samples. The curve nearly plateaus when sufficient sequence data are included, with few novel genes being left undetected.

Additional file 24: Figure S6. The racehorse gut is rich in microbes that can synthesize acetate and butyrate. The microbes enriched in racehorses contain a large number of enzymes that synthesize acetate and butyrate. At the bottom of the heatmap are the difference MAG ID, and the top are the taxonomic information of the MAG.

Additional file 13: Figure S3. Overview of 11 circular genomes. From the outside to the inside, the concentric circles indicate the positional coordinates of the genomic sequence, coding genes, gene annotation, noncoding RNAs, genomic GC content, and genomic GC skew values. Gene annotation: different colours are used to distinguish different terms of the KEGG and GO annotations. Genome GC content: the inner, red part indicates that the GC content of the region is less than the average GC content of the whole genome; the outer, green part indicates that the GC content of the region is greater than the average value. GC skew value: the inner, pink part indicates that the G content in the area is less than the C content; the outer, light-green part indicates that the G content in the area is greater than the C content.

The simulations of atmospheric cloud-radiative effect (ACRE) from 54 Coupled Model Intercomparison Project phase 6 (CMIP6) models during the historical period of 2000/03–2014/12 are compared and evaluated against the satellite-based Clouds and the Earth’s Radiant Energy System (CERES) products. For ease of comparison, all CMIP6 models are divided into high-, medium-, and low-resolution groups to examine the potential impact of model horizontal resolution change on the simulations of ACRE distribution over the tropical oceans. The results show that ACRE is positive inside the ITCZs but negative in the subtropics and cold tongue areas, owing to the very different radiative forcing between deep and shallow clouds. Simulations of ACRE are sensitive to the model horizontal resolution used and the finer resolution models generally produce a better performance of ACRE simulations against the CERES observations. The reduced ACRE biases in finer resolution models are mainly contributed by the improved longwave ACRE (i.e., LWACRE) simulations, especially over the Pacific and Atlantic cold tongue areas where shallow stratocumulus clouds prevail.

Neddylation is a type of posttranslational protein modification that has been observed to be overactivated in various cancers. UBC12 is one of two key E2 enzymes in the neddylation pathway. Reports indicate that UBC12 deficiency may suppress lung cancer cells, such that UBC12 could play an important role in tumor progression. However, systematic studies regarding the expression profile of UBC12 in cancers and its relationship to cancer prognosis are lacking. In this study, we comprehensively analyzed UBC12 expression in diverse cancer types and found that UBC12 is markedly overexpressed in most cancers (17/21), a symptom that negatively correlates with the survival rates of cancer patients, including gastric cancer. These results demonstrate the suitability of UBC12 as a potential target for cancer treatment. Currently, no effective inhibitor targeting UBC12 has been discovered. We screened a natural product library and found, for the first time, that arctigenin has been shown to significantly inhibit UBC12 enzyme activity and cullin neddylation. The inhibition of UBC12 enzyme activity was newly found to contribute to the effects of arctigenin on suppressing the malignant phenotypes of cancer cells. Furthermore, we performed proteomics analysis and found that arctigenin intervened with cullin downstream signaling pathways and substrates, such as the tumor suppressor PDCD4. In summary, these results demonstrate the importance of UBC12 as a potential therapeutic target for cancer treatment, and, for the first time, the suitability of arctigenin as a potential compound targeting UBC12 enzyme activity. Thus, these findings provide a new strategy for inhibiting neddylation-overactivated cancers.

In this study, we have facilely developed a SnO2-based electrocatalyst (SnO2-VO@N-C), which can combine together the favorable structure features of oxygen vacancies, porosity, and full-coating with N-doped carbon layers (N-C). Our experimental and theoretical calculation results indicated that with the facile engineering of oxygen vacancies and the full-coating of the N-doped carbon layer, the adsorption/activation of CO2 and charge transfer can be promoted in the CO2 reduction process, making SnO2-VO@N-C the electrocatalyst with improved activity and selectivity (FEHCOOH = 84%) toward the reduction of CO2 to HCOOH.

Gastrointestinal tumors have become a worldwide health problem with high morbidity and poor clinical outcomes. Chemotherapy and surgery, the main treatment methods, are still far from meeting the treatment needs of patients, and targeted therapy is in urgent need of development. Recently, emerging evidence suggests that kelch-like (KLHL) proteins play essential roles in maintaining proteostasis and are involved in the progression of various cancers, functioning as adaptors in the E3 ligase complex and promoting the specific degradation of substrates. Therefore, KLHL proteins should be taken into consideration for targeted therapy strategy discovery. This review summarizes the current knowledge of KLHL proteins in gastrointestinal tumors and discusses the potential of KLHL proteins as potential drug targets and prognostic biomarkers.

Jing-Bo Liu,1 Qiao-Jun Zhang,2 Jian-Zhi Liu,1 Wen-Ting Zhang,3 Yi Li,3 Hao-Hong Li,3 Zhi-Rong Chen,3 Da-Li Zheng2 1Department of Otorhinolaryngology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, People’s Republic of China; 2Fujian Key Laboratory of Oral Diseases, Fujian Biological Materials Engineering and Technology Center of Stomatology, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian 350004, People’s Republic of China; 3College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116, People’s Republic of ChinaCorrespondence: Da-Li ZhengFujian Key Laboratory of Oral Diseases, Fujian Biological Materials Engineering and Technology Center of Stomatology, School and Hospital of Stomatology, Fujian Medical University, 88 Jiaotong Road, Fuzhou 350004, People’s Republic of ChinaTel +86-591-83720599Email dalizheng@fjmu.edu.cnJian-Zhi LiuDepartment of Otorhinolaryngology, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, People’s Republic of ChinaTel +86-591- 83357896Email liujianzhi@aliyun.comBackground: The realization of multifunction in one bulk material is fascinating for developing a new generation of devices. Quaternary phosphorus salts were seldom utilized as templates in haloargentate systems, and the hybridization of alkyl(triphenyl)phosphonium with halometallate will be a good strategy for the development of multifunctional material, especially for biological material.Methods: Under the template of (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 3, 4), three bromoargentate hybrids were constructed via the solution method, ie, (1,2-DBTPP)(Ag2Br4) ( 1), {(1,3-DBTPP)2(Ag7Br11)]∙CH3CN∙H2O}n ( 2), and {[(1,4-DBTPP)(Ag5Br7)](CH3CN)2∙H2O}n ( 3) (1,2-DBTPP2+=ethane-1,2-diylbis (triphenyl)phosphonium, 1,3-DBTPP2+=propane-1,3-diylbis (triphenyl)phosphonium, 1,4-DBTPP2+=butane-1,4-diylbis (triphenyl)phosphonium)).Results: The (Ag7Br11)n4n- chain in 2 is a new type of 1-D bromoargentate chain constructed from cubane-like Ag4Br4 nodes, AgBr4 tetrahedrons and AgBr3 triangles. Interestingly, by elongating spacer n from 2 to 4, argentophilicity interactions are weakened, and the hydrogen bonds are strengthened. Consequently, their water stabilities and photocurrents are improved, in which the Ag-4d/Br-4p to π* anti-bonding orbital of the quaternary phosphorus transfer is facilitated. Furthermore, the greenish blue emissions can be detected. Finally, high inhabitation rates against Streptococcus mutans and Candida albicans can be observed in 2 and 3.Conclusion: In all experiments, by elongating the spacer lengths of quaternary phosphorus salts, multifunctions were integrated in the quaternary phosphorus/bromoargentate hybrids, including greenish blue luminescence, repeatable photocurrent responses and durable antimicrobial activities with enhanced water stability. This work could provide a theoretical guide for the design of new biologically multifunctional materials.Keywords: quaternary phosphorus, bromoargentates, nanoparticles, luminescence, antimicrobial

In this paper, we propose a fuzzy logic algorithm to recognize the types of hydrometeors by using Ka and Ku reflectivity factors, temperature thresholds and an asymmetric t-form membership function. The identifiable types of hydrometeors include snow, graupel, mixed-phase particles, large raindrops, and small raindrops. The reflectivity detection data of Ka and Ku with attenuation correction is from dual-frequency precipitation radar onboard the global precipitation measurement satellite. The temperature data from the European Centre for Medium-range Weather Forecasts are used to identify the hydrometeors, and the identified hydrometeors are compared with the vertical profiles of phase from official level-2 DPR products. The results show that the identified hydrometeors are reasonable and reveal the evolution process of tropical cyclones, which can be further applied to the study of precipitation microphysical process and artificial precipitation.

Direct electrosynthesis of hydrogen peroxide (H

Studying the effect of the coordination field on the catalytic property is critical for the rational design of outstanding electrocatalysts for H

Although thunder god vine (Tripterygium wilfordii) has been widely used for treatment of idiopathic membranous nephropathy (IMN), the pharmacological mechanisms underlying its effects are still unclear. This study investigated potential therapeutic targets and the pharmacological mechanism of T. wilfordii for the treatment of IMN based on network pharmacology. Active components of T. wilfordii were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. IMN-associated target genes were collected from the GeneCards, DisGeNET, and OMIM databases. VENNY 2.1 was used to identify the overlapping genes between active compounds of T. wilfordii and IMN target genes. The STRING database and Cytoscape 3.7.2 software were used to analyze interactions among overlapping genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the targets were performed using Rx64 4.0.2 software, colorspace, stringi, DOSE, clusterProfiler, and enrichplot packages. A total of 153 compound-related genes and 1485 IMN-related genes were obtained, and 45 core genes that overlapped between both categories were identified. The protein–protein interaction network and MCODE results indicated that the targets TP53, MAPK8, MAPK14, STAT3, IFNG, ICAM1, IL4, TGFB1, PPARG, and MMP1 play important roles in the treatment of T. wilfordii on IMN. Enrichment analysis showed that the main pathways of targets were the AGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and Toll-like receptor signaling pathway. This study revealed potential multi-component and multi-target mechanisms of T. wilfordii for the treatment of IMN based on network pharmacological, and provided a scientific basis for further experimental studies.

Apramycin is a structurally unique member of the 2-deoxystreptamine class of aminoglycoside antibiotics characterized by a monosubstituted 2-deoxystreptamine ring that carries an unusual bicyclic eight-carbon dialdose moiety. Because of its unusual structure, apramycin is not susceptible to the most prevalent mechanisms of aminoglycoside resistance including the aminoglycoside-modifying enzymes and the ribosomal methyltransferases whose widespread presence severely compromises all aminoglycosides in current clinical practice. These attributes coupled with minimal ototoxocity in animal models combine to make apramycin an excellent starting point for the development of next-generation aminoglycoside antibiotics for the treatment of multidrug-resistant bacterial infections, particularly the ESKAPE pathogens. With this in mind, we describe the design, synthesis, and evaluation of three series of apramycin derivatives, all functionalized at the 5-position, with the goals of increasing the antibacterial potency without sacrificing selectivity between bacterial and eukaryotic ribosomes and of overcoming the rare aminoglycoside acetyltransferase (3)-IV class of aminoglycoside-modifying enzymes that constitutes the only documented mechanism of antimicrobial resistance to apramycin. We show that several apramycin-5-O-β-d-ribofuranosides, 5-O-β-d-eryrthofuranosides, and even simple 5-O-aminoalkyl ethers are effective in this respect through the use of cell-free translation assays with wild-type bacterial and humanized bacterial ribosomes and of extensive antibacterial assays with wild-type and resistant Gram negative bacteria carrying either single or multiple resistance determinants. Ex vivo studies with mouse cochlear explants confirm the low levels of ototoxicity predicted on the basis of selectivity at the target level, while the mouse thigh infection model was used to demonstrate the superiority of an apramycin-5-O-glycoside in reducing the bacterial burden in vivo.

At present, whether α2-adrenoceptors in the prelimbic cortex (PrL) are involved in Parkinson's disease-related anxiety is unclear. We examined the effects of PrL α2-adrenoceptors on anxiety-like behaviors in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. Compared to the sham operation, the lesion induced anxiety-like responses as measured by the open field test and elevated plus-maze test. Intra-PrL injection of the α2-adrenoceptor agonist clonidine (1.25, 2.5 or 5 μg/rat) produced anxiolytic effects in sham-operated and lesioned rats. Furthermore, intra-PrL injection of the α2-adrenoceptor antagonist idazoxan (1, 2 or 4 μg/rat) induced anxiogenic effects in two groups of rats. The effective doses produced by clonidine and idazoxan in lesioned rats were higher than those in sham-operated rats. Neurochemical results showed that intra-PrL injection of clonidine (5 μg/rat) or idazoxan (4 μg/rat) decreased or increased dopamine (DA) and noradrenaline (NA) and serotonin (5-HT) levels in the medial prefrontal cortex (mPFC) and amygdala in sham-operated and lesioned rats, respectively. These results suggest that α2-adrenoceptors in the PrL are involved in the regulation of anxiety-like behaviors, which is attributable to changes in DA, NA and 5-HT levels in the mPFC and amygdala after activation and blockade of α2-adrenoceptors.

Three novel donor-π-acceptor two-photon absorption compounds (1PZPy, 2PZIm, 3CZPy) bearing the 10-butyl-10H-phenothiazine (9-butyl-9H-carbazole) donor, the pyridinium (benzimidazolium) acceptor, and the 2,5-divinylthiophene π-bridge were synthesized and fully characterized by

The molecular characteristics, genetic relationships within the population and dispersal patterns ofTheThis study revealed for the first time the molecular characteristics, genetic diversity and dispersal patterns of

Diabetes mellitus is a fast-growing disease with a major influence on people's quality of life. Oral hypoglycemic drugs and insulin are currently the main effective drugs in the treatment of diabetes, but chronic consumption of these drugs has certain side effects. Polysaccharides, saponins, flavonoids, and phenolics are the primary secondary metabolites isolated from the rhizomes of

In this study, we have facilely developed a SnO