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Abstract Background Hypercoagulability emerges as a central pathological feature and clinical complication in nephrotic syndrome. Increased platelet activation and aggregability are closely related to hypercoagulability in nephrotic syndrome. Monocyte-platelet aggregates (MPAs) have been proposed to represent a robust biomarker of platelet activation. The aim of this study was to investigate levels of the circulating MPAs and MPAs with the different monocyte subsets to evaluate the association of MPAs with hypercoagulability in nephrotic syndrome. Methods Thirty-two patients with nephrotic syndrome were enrolled. In addition, thirty-two healthy age and sex matched adult volunteers served as healthy controls. MPAs were identified by CD14 monocytes positive for CD41a platelets. The classical (CD14 + + CD16-, CM), the intermediate (CD14 + + CD16+, IM) and the non-classical (CD14 + CD16++, NCM) monocytes, as well as subset specific MPAs, were measured by flow cytometry. Results Patients with nephrotic syndrome showed a higher percentage of circulating MPAs as compared with healthy controls (p

Introduction: We here describe a new method for distinguishing authentic Bletilla striata from similar decoctions (namely, Gastrodia elata, Polygonatum odoratum, and Bletilla ochracea schltr).Methods: Preliminary identification and analysis of four types of decoction pieces were conducted following the Chinese Pharmacopoeia and local standards. Intelligent sensory data were then collected using an electronic nose, an electronic tongue, and an electronic eye, and chromatography data were obtained via high-performance liquid chromatography (HPLC). Partial least squares discriminant analysis (PLS-DA), support vector machines (SVM), and back propagation neural network (BP-NN) models were built using each set of single-source data for authenticity identification (binary classification of B. striata vs. other samples) and for species determination (multi-class sample identification). Features were extracted from all datasets using an unsupervised approach [principal component analysis (PCA)] and a supervised approach (PLS-DA). Mid-level data fusion was then used to combine features from the four datasets and the effects of feature extraction methods on model performance were compared.Results and Discussion: Gas chromatography–ion mobility spectrometry (GC-IMS) showed significant differences in the types and abundances of volatile organic compounds between the four sample types. In authenticity determination, the PLS-DA and SVM models based on fused latent variables (LVs) performed the best, with 100% accuracy in both the calibration and validation sets. In species identification, the PLS-DA model built with fused principal components (PCs) or fused LVs had the best performance, with 100% accuracy in the calibration set and just one misclassification in the validation set. In the PLS-DA and SVM authenticity identification models, fused LVs performed better than fused PCs. Model analysis was used to identify PCs that strongly contributed to accurate sample classification, and a PC factor loading matrix was used to assess the correlation between PCs and the original variables. This study serves as a reference for future efforts to accurately evaluate the quality of Chinese medicine decoction pieces, promoting medicinal formulation safety.

Stem cells have self-renewal, replication, and multidirectional differentiation potential, while progenitor cells are undifferentiated, pluripotent or specialized stem cells. Stem/progenitor cells secrete various factors, such as cytokines, exosomes, non-coding RNAs, and proteins, and have a wide range of applications in regenerative medicine. However, therapies based on stem cells and their secreted exosomes present limitations, such as insufficient source materials, mature differentiation, and low transplantation success rates, and methods addressing these problems are urgently required. Ultrasound is gaining increasing attention as an emerging technology. Low-intensity pulsed ultrasound (LIPUS) has mechanical, thermal, and cavitation effects and produces vibrational stimuli that can lead to a series of biochemical changes in organs, tissues, and cells, such as the release of extracellular bodies, cytokines, and other signals. These changes can alter the cellular microenvironment and affect biological behaviors, such as cell differentiation and proliferation. Here, we discuss the effects of LIPUS on the biological functions of stem/progenitor cells, exosomes, and non-coding RNAs, alterations involved in related pathways, various emerging applications, and future perspectives. We review the roles and mechanisms of LIPUS in stem/progenitor cells and exosomes with the aim of providing a deeper understanding of LIPUS and promoting research and development in this field.

This paper focuses on determining the authenticity and identifying the species of Fritillariae cirrhosae using electronic nose, electronic tongue, and electronic eye sensors, near infrared and mid-level data fusion. 80 batches of Fritillariae cirrhosae and its counterfeits (including several batches of Fritillaria unibracteata Hsiao et K.C. Hsia, Fritillaria przewalskii Maxim, Fritillaria delavayi Franch and Fritillaria ussuriensis Maxim) were initially identified by Chinese medicine specialists and by criteria in the 2020 edition of Chinese Pharmacopoeia. After obtaining the information from several sensors we constructed single-source PLS-DA models for authenticity identification and single-source PCA-DA models for species identification. We selected variables of interest by VIP value and Wilk’s lambda value, and we subsequently constructed the three-source fusion model of intelligent senses and the four-source fusion model of intelligent senses and near-infrared spectroscopy. We then explained and analyzed the four-source fusion models based on the sensitive substances detected by key sensors. The accuracies of single-source authenticity PLS-DA identification models based on electronic nose, electronic eye, electronic tongue sensors and near-infrared were respectively 96.25%, 91.25%, 97.50% and 97.50%. The accuracies of single-source PCA-DA species identification models were respectively 85%, 71.25%, 97.50% and 97.50%. After three-source data fusion, the accuracy of the authenticity identification of the PLS-DA identification model was 97.50% and the accuracy of the species identification of the PCA-DA model was 95%. After four-source data fusion, the accuracy of the authenticity of the PLS-DA identification model was 98.75% and the accuracy of the species identification of the PCA-DA model was 97.50%. In terms of authenticity identification, four-source data fusion can improve the performance of the model, while for the identification of the species the four-source data fusion failed to optimize the performance of the model. We conclude that electronic nose, electronic tongue, electronic eye data and near-infrared spectroscopy combined with data fusion and chemometrics methods can identify the authenticity and determine the species of Fritillariae cirrhosae. Our model explanation and analysis can help other researchers identify key quality factors for sample identification. This study aims to provide a reference method for the quality evaluation of Chinese herbs.

In humans and animals, exposure to changes in internal or external environments causes acute stress, which changes sleep and enhances neurochemical, neuroendocrine, and sympathetic activities. Repeated stress responses play an essential role in the pathogenesis of psychiatric diseases and sleep disorders. However, the underlying mechanism of sleep changes and anxiety disorders in response to acute stress is not well established. In the current study, the effects of restraint stress (RS) on anxiety and sleep–wake cycles in mice were investigated. We found that after RS, the mice showed anxiety-like behavior after RS manipulation and increased the amounts of both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in the dark period. The increase in sleep time was mainly due to the increased number of episodes of NREM and REM sleep during the dark period. In addition, the mice showed an elevation of the EEG power spectrum of both NREM and REM sleep 2 h after RS manipulation. There was a significant reduction in the EEG power spectrum of both NREM and REM sleep during the darkperiod in the RS condition. The expression of the c-Fos protein was significantly increased in the parabrachial nucleus, bed nucleus of the stria terminalis, central amygdala, and paraventricular hypothalamus by RS manipulation. Altogether, the findings from the present study indicated that neural circuits from the parabrachial nucleus might regulate anxiety and sleep responses to acute stress, and suggest a potential therapeutic target for RS induced anxiety and sleep alterations.

Major depressive disorder is one of the most common neuropsychiatric diseases and it is a global public health problem that leads to disabilities. Currently, there is a growing need to explore novel strategy to cure major depressive disorder due to the limitation of available treatments. Rannasangpei (RSNP) is a traditional Tibetan medicine which acts as a therapeutic agent in various acute or chronic diseases, including cardiovascular diseases and neurodegenerative diseases. Crocin-1 a coloring ingredient of saffron which exhibited anti-oxidative and anti-inflammatory properties. Here, we aimed to illustrate whether RSNP and its active ingredient crocin-1 rescue depressive-like phenotypes in chronic unpredictable mild stress (CUMS) induced mouse model of depression. Our results showed that peripheral administration of RSNP or crocin-1 ameliorated the depressive-like behaviors in CUMS-treated mice, as demonstrated by the forced swimming test and tail suspension test. Furthermore, RSNP or crocin-1 treatment reduced oxidative stress in the peripheral blood and hippocampus of the CUMS-treated mice. Additionally, the dysregulated immune system response, as demonstrated by the increased expression of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6) and the decreased expression of the anti-inflammatory factor-interleukin-10 in the prefrontal cortex and/or hippocampus of CUMS-treated mice, were at least partially restored by RSNP or crocin-1 treatment. RSNP or crocin-1 also restored apoptotic protein marker (Bcl-2 and Bax) levels in the prefrontal cortex and hippocampus of the CUMS-treated mice. Moreover, our data indicated that RSNP or crocin-1 increased astrocyte number and brain-derived neurotrophic factor levels in the hippocampus of CUMS-treated mice after RSNP or crocin-1 administration. Taken together, our study for the first time revealed an anti-depressant effect of RSNP and its active ingredient crocin-1 in a mouse model of depression, with involvement of oxidative stress, inflammatory response and apoptotic pathway.

Peroxisomes have been proved playing roles in infection of several plant pathogens. Although the contribution of a portion of peroxins in pathogenicity was demonstrated, most of them are undocumented in fungi, especially, Botrytis cinerea. The homologs of Pex8, Pex10, and Pex12 in B. cinerea were functionally characterized in this work using gene disruption strategies. Compared with the wild-type strain (WT), the Δbcpex8, Δbcpex10, and Δbcpex12 mutants exhibited significant reduction in melanin production, fatty acid utilization, and decreased tolerance to high osmotic pressure and reactive oxygen species (ROS). The mycelial growth and conidiation of were significantly inhibited in Δbcpex8, Δbcpex10, and Δbcpex12 strains. The mycelial growth rates of Δbcpex8, Δbcpex10, and Δbcpex12 were reduced by 32, 35, and 34%, respectively, compared with WT and ectopic transformant (ET), and the conidiation was reduced by approximately 89, 27, and 88%, respectively. The conidial germination, germ tube elongation, and the formation of initiate infection structures (IFSs) were also reduced by the deletion of the genes. The pathogenicity was tested on the leaves of tobacco and strawberry, and fruits of tomato. On the leaves of tobacco and strawberry, the Δbcpex8, Δbcpex10, and Δbcpex12 mutants could not induce necrotic lesions, and the lesions on tomato fruits infected with the mutants were significantly reduced than those of the wide type. The results indicated that BcPEX8, BcPEX10, and BcPEX12 are indispensable for the development and pathogenicity of B. cinerea.

Chimeric antigen receptor-T (CAR-T) cell therapy is a breakthrough for B-cell hematological malignancies but is commonly associated with cytokine release syndrome and neurotoxicity and is occasionally complicated by neurological symptoms, such as cognitive disturbances. Currently, no effective treatments for CAR-T therapy-related cognitive impairment are available. Here, we present a 22-year-old patient with cognitive impairment who was treated with CAR-T cells as a salvage therapy for Burkitt lymphoma. One month after CAR-T cell infusion, he experienced memory loss that mainly manifested as forgetting recent-onset events. Two months of rehabilitation and hyperbaric oxygen therapy failed to provide clinical improvement. Subsequently, the patient improved with oral oxiracetam for 5 months. However, after 10 months of withdrawal, he showed significantly worse memory decline. Then, he began to take sodium oligomannate (22 February 2021). Follow-up testing at 6 and 12 months revealed maintenance of memory gains with sodium oligomannate alone or in combination with rivastigmine. Our case shows that CAR-T therapy may compromise cognitive function and that sodium oligomannate may have partial efficacy in restoring cognitive performance and activities of daily living. This may provide insights for further applications of sodium oligomannate for neurological symptoms, especially cognitive deficits following CAR-T cell therapy.

BackgroundCerebral blood flow (CBF) alterations are involved in the onset and progression of Alzheimer’s disease (AD) and can be a potential biomarker. However, CBF measured by single-delay arterial spin labeling (ASL) for discrimination of mild cognitive impairment (MCI, an early stage of AD) was lack of accuracy. Multi-delay ASL can not only provide CBF quantification but also provide arterial transit time (ATT). Unfortunately, the technique was scarcely applied to the diagnosis of AD. Here, we detected the utility of ASL with 1-delay and 7-delay in ten regions of interest (ROIs) to identify MCI and AD.Materials and MethodsPseudocontinuous ASL (pCASL) MRI was acquired on a 3T GE scanner in adults from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) Study of AD cohort, including 26 normal cognition (NC), 37 MCI, and 39 AD. Receiver operating characteristic (ROC) analyses with 1-delay and 7-delay ASL were performed for the identification of MCI and AD. The DeLong test was used to compare ROC curves.ResultsFor CBF of 1-delay or 7-delay the AUCs showed moderate-high performance for the AD/NC and AD/MCI comparisons (AUC = 0.83∼0.96) (p < 0.001). CBF of 1-delay performed poorly in MCI/NC comparison (AUC = 0.69) (p < 0.001), but CBF of 7-delay fared well with an AUC of 0.79 (p < 0.001). The combination of CBF and ATT of 7-delay showed higher performance for AD/NC, AD/MCI, and MCI/NC comparisons with AUCs of 0.96, 0.89, and 0.89, respectively (p < 0.001). Furthermore, combination of CBF, ATT, sex, age, APOE ε4, and education improved further the accuracy (p < 0.001). In subgroups analyses, there were no significant differences in CBF of 7-delay ASL for identification of AD or MCI between age subgroups (p > 0.05).ConclusionThe combination of CBF and ATT with 7-delay ASL showed higher performance for identification of MCI than CBF of 1-delay, when adding to sex, age, APOE ε4 carrier status, and education years, the diagnostic performance was further increased, presenting a potential imaging biomarker in early AD.

Podoplanin (PDPN) promotes platelet aggregation and activation by interacting with C-type lectin-like receptor 2(CLEC-2) on platelets. The interaction between the upregulated PDPN and platelet CLEC-2 stimulates venous thrombosis. PDPN was identified as a risk factor for coagulation and thrombosis in inflammatory processes. Hypercoagulability is defined as the tendency to develop thrombosis according to fibrinogen and/or D dimer levels. Nephrotic syndrome is also considered to be a hypercoagulable state. The aim of this study is to investigate the association of soluble PDPN/CLEC-2 with hypercoagulability in nephrotic syndrome. Thirty-five patients with nephrotic syndrome and twenty-seven healthy volunteers were enrolled. PDPN, CLEC-2 and GPVI concentrations were tested by enzyme-linked immunosorbent assay (ELISA). Patients with nephrotic syndrome showed higher serum levels of PDPN and GPVI in comparison to healthy controls ( P 5.88 ng/ml, the risk of hypercoagulability was significantly increased in nephrotic syndrome (OR = 22.79, 95% CI 5.92-87.69, P

ObjectiveThis study aimed to investigate the training experiences and needs of intensive care unit (ICU) general nurses against a background of regular Coronavirus disease (COVID-19) prevention and control.MethodsUsing the phenomenological method of qualitative research, semi-structured interviews were conducted with 10 ICU nurses. The interview data were analyzed, sorted, summarized, and refined using the content analysis method.ResultsThe following five themes were extracted from the interviews, based on the training experiences of the nurses: 1) broadening their thinking; 2) discovering their personal shortcomings; 3) gaining self-confidence; 4) calmly facing frontline work; 5) experiencing high assessment pressure. The training needs of the nurses could be summarized into the following four themes: 1) increased training time; 2) improving the assessment mechanism; 3) establishing a normal rotating-shift training system; 4) balancing the teaching levels.ConclusionAgainst a background of regular epidemic prevention and control, ICU training for general nurses is of high practical significance and value. Thus, active exploration and research should be conducted to establish perfect training and assessment mechanisms for these nurses. Additionally, training methods that are suitable for clinical needs should be formulated and training systematization and standardization must be promoted.

BackgroundThe ε4 allele of the apolipoprotein E (APOE) gene is a strong genetic risk factor for aging-related cognitive decline. However, the causal connection between ε4 alleles and cognition is not well understood. The objective of this study was to identify the roles of cerebral blood flow (CBF) in cognitive-related brain areas in mediating the associations of APOE with cognition.MethodsThe multiple linear regression analyses were conducted on 369 subjects (mean age of 68.8 years; 62.9% of women; 29.3% of APOE ε4 allele carriers). Causal mediation analyses with 5,000 bootstrapped iterations were conducted to explore the mediation effects.ResultAPOE ε4 allele was negatively associated with cognition (P < 0.05) and CBF in the amygdala, hippocampus, middle temporal gyrus, posterior cingulate, and precuneus (all P < 0.05). The effect of the APOE genotype on cognition was partly mediated by the above CBF (all P < 0.05).ConclusionCBF partially mediates the potential links between APOE genotype and cognition. Overall, the APOE ε4 allele may lead to a dysregulation of the vascular structure and function with reduced cerebral perfusion, which in turn leads to cognitive impairment.

Background: The potential correlation between patent foramen ovale (PFO) and migraine has been previously reported, but whether PFO closure plays a role in reducing migraine burden has not reached an agreement. Method: We searched PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Science Technology Periodical Database and China Biology Medicine Database (CBM) through September 30, 2021 to identify associations between PFO closure and outcome of migraine burden. The control groups consisted of drug treatment or sham procedure. Result: Three randomized clinical trials (RCT) and 9 case-control studies were eligible for inclusion (1754 participants), of which 7 reported nonrecurrence of migraine, 4 reported reduced migraine-frequency and migraine-days, and 5 reported HIT-6 score and 4 reported MIDAS score. The mean (SD) age of participants was 40.68 (3.81) years and 1340 (76.39%) were women. PFO closure was significantly associated with a reduced risk of migraine-recurrence by 4.47 (95% CI, 2.94–6.80; I2 = 12%), frequency of migraine by 0.35 (95% CI, 0.17–0.53; I2 = 0%) and monthly migraine days by 0.28 (95% CI, 0.10–0.46), and decreased score of HIT-6 (SMD 1.23, 95 %CI 0.52–1.95, I2 = 93%). Conclusion: Transcatheter PFO closure is significantly associated with burden reduction of migraine headache.

Abstract Background The fungal communities inhabiting natural Ophiocordyceps sinensis play critical ecological roles in alpine meadow ecosystem, contribute to infect host insect, influence the occurrence of O. sinensis, and are repertoire of potential novel metabolites discovery. However, a comprehensive understanding of fungal communities of O. sinensis remain elusive. Therefore, the present study aimed to unravel fungal communities of natural O. sinensis using combination of high-throughput sequencing and culture-dependent approaches. Results A total of 280,519 high-quality sequences, belonging to 5 fungal phyla, 15 classes, 41 orders, 79 families, 112 genera, and 352 putative operational taxonomic units (OTUs) were obtained from natural O. sinensis using high-throughput sequencing. Among of which, 43 genera were identified in external mycelial cortices, Ophiocordyceps, Sebacinia and Archaeorhizomyces were predominant genera with the abundance of 95.86, 1.14, 0.85%, respectively. A total of 66 genera were identified from soil microhabitat, Inocybe, Archaeorhizomyces, unclassified Thelephoraceae, Tomentella, Thelephora, Sebacina, unclassified Ascomycota and unclassified fungi were predominant genera with an average abundance of 53.32, 8.69, 8.12, 8.12, 7.21, 4.6, 3.08 and 3.05%, respectively. The fungal communities in external mycelial cortices were significantly distinct from soil microhabitat. Meanwhile, seven types of culture media were used to isolate culturable fungi at 16 °C, resulted in 77 fungal strains identified by rDNA ITS sequence analysis, belonging to 33 genera, including Ophiocordyceps, Trichoderma, Cytospora, Truncatella, Dactylonectria, Isaria, Cephalosporium, Fusarium, Cosmospora and Paecilomyces, etc.. Among all culturable fungi, Mortierella and Trichoderma were predominant genera. Conclusions The significantly differences and overlap in fungal community structure between two approaches highlight that the integration of high-throughput sequencing and culture-dependent approaches would generate more information. Our result reveal a comprehensive understanding of fungal community structure of natural O. sinensis, provide new insight into O. sinensis associated fungi, and support that microbiota of natural O. sinensis is an untapped source for novel bioactive metabolites discovery.

Objective To investigate the clinical and imaging differences between limb⁃girdle muscular dystrophy type 2B (LGMD2B) and immune⁃mediated necrotizing myopathy (IMNM). Methods Forty⁃five patients with LGMD2B and 45 patients with IMNM from January 2014 to December 2018 were included. Sex, age of onset, age of diagnosis and time of delay in admission were recorded, and serum creatine kinase (CK) level was measured. Cervical flexion, proximal and distal upper limbs, proximal and distal lower limbs were evaluated by Medical Research Council (MRC) Level 6 and muscle strength percentages were calculated. Skeletal muscle fatty infiltration and edema degree on both thighs were evaluated by MRI. Results The onset age (Z=⁃3.605, P=0.000) and diagnosis age (Z=⁃2.757, P= 0.006) of LGMD2B patients were earlier than those of IMNM patients, while the delay time of admission was longer than that of IMNM patients (Z=⁃4.749, P=0.000), the serum CK was higher than that of IMNM patients (Z=⁃2.247, P=0.025). The muscle strength of neck flexion (Z=⁃6.320, P=0.000)and percentage of muscle strength(t=⁃6.320, P=0.000),the muscle strengh of proximal uppe rextremities (Z=⁃3.528, P= 0.000)and percentage of muscle strength (t=⁃3.762, P=0.000)in IMNM patients were lower than those in LGMD2B patients, while the muscle strengh of distal lower extremity (Z=⁃ 3.256, P=0.001) and percentage of muscle strength (t=⁃2.883, P=0.004) in LGMD2B patients were lower than those in IMNM patients. LGMD2B patients had higher muscle fatty infiltration degree in anterior group (Z=⁃3.119, P= 0.002)and posterior group (Z=⁃2.534, P=0.011)of thigh muscle than IMNM patients, but IMNM patients had highter thigh muscle edema degree in posterior group than LGMD2B patients (Z=⁃3.887, P=0.000). Conclusions Compared with IMNM patients, LGMD2B patients had earlier onset age, longer delay in diagnosis time, worse muscle strength of distal lower extremities, higher serum CK and more obviously thigh muscle fatty infiltration. In IMNM patients, muscle weakness of neck flexion and proximal upper extremities, thigh muscle edema of posterior group were more obvious. These characteristics contribute to the clinical differentiation of the two diseases. DOI：10.3969/j.issn.1672⁃6731.2020.09.004

Abstract We study the two-body anti-triplet charmed baryon decays based on the diagrammatic approach with SU(3) flavor symmetry. We extract the two W -exchange effects as E B and E' that contribute to the Λ c + → Ξ 0 K + $$ {\Lambda}_c^{+}\to {\Xi}^0{K}^{+} $$ decay, together with the relative phases, where E B gives the main contribution. Besides, we find that B Λ c + → p π 0 = 0.8 − 0.8 + 0.9 × 10 − 4 $$ \mathcal{B}\left({\Lambda}_c^{+}\to p{\pi}^0\right)=\left({0.8}_{-0.8}^{+0.9}\right)\times {10}^{-4} $$ ,which is within the experimental upper bound. Particularly, we obtain B Ξ c + → Ξ 0 π + = 9.3 ± 3.6 × 10 − 3 $$ \mathcal{B}\left({\Xi}_c^{+}\to {\Xi}^0{\pi}^{+}\right)=\left(9.3\pm 3.6\right)\times {10}^{-3} $$ , B Ξ c 0 → Ξ − π + Λ 0 K ¯ 0 = 19.3 ± 2.8 8.3 ± 5.0 × 10 − 2 $$ \mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{\pi}^{+},{\Lambda}^0{\overline{K}}^0\right)=\left(19.3\pm 2.8,8.3\pm 5.0\right)\times {10}^{-2} $$ and B Ξ c 0 → Ξ − K + = 5.6 ± 0.8 × 10 − 4 $$ \mathcal{B}\left({\Xi}_c^0\to {\Xi}^{-}{K}^{+}\right)=\left(5.6\pm 0.8\right)\times {10}^{-4} $$ , which all agree with the data. For the singly Cabibbo suppressed Λ c + $$ {\Lambda}_c^{+} $$ decays, we predict that B Λ c + → n π + pη ' Σ + K 0 = 7.7 ± 2.0 7.1 ± 1.4 19.1 ± 4.8 × 10 − 4 $$ \mathcal{B}\left({\Lambda}_c^{+}\to n{\pi}^{+}, p\eta \hbox{'},{\Sigma}^{+}{K}^0\right)=\left(7.7\pm 2.0,7.1\pm 1.4,19.1\pm 4.8\right)\times 10-4 $$ , which are accessible to the experiments at BESIII, BELLEII and LHCb.

Abstract. Background:. Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression. Methods:. The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed. Results:. Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios+ Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA. Conclusion:. Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.

Colony-stimulating factor-1 receptor-microglial encephalopathy is a rare rapidly progressive dementia resulting from colony-stimulating factor-1 receptor (CSF1R) mutations, also named pigmentary orthochromatic leukodystrophy (POLD), hereditary diffuse leukoencephalopathy with spheroids (HDLS), adult-onset leukoencephalopathy with axonal spheroids, and pigmented glia (ALSP) and CSF1R-related leukoencephalopathy. CSF1R is primarily expressed in microglia and mutations normally directly lead to changes in microglial number and function. Many animal models have been constructed to explore pathogenic mechanisms and potential therapeutic strategies, including zebrafish, mice, and rat models which are with CSF1R monogenic mutation, biallelic or tri-allelic deletion, or CSF1R-null. Although there is no cure for patients with CSF1R-microglial encephalopathy, microglial replacement therapy has become a topical research area. This review summarizes CSF1R-related pathogenetic mutation sites and mechanisms, especially the feasibility of the microglia-original immunotherapy.

This review describes recent advances in copper-catalyzed difluoroalkylation reactions. The RCF2 radical is generally proposed in the mechanism of these reactions. At present, various types of copper-catalyzed difluoroalkylation reactions have been realized. According to their characteristics, we classify these difluoroalkylation reactions into three types.

Background: Plasma-based biomarkers would be potential biomarkers for early diagnosis of Alzheimer's disease (AD) because they are more available and cost-effective than cerebrospinal fluid (CSF) or neuroimaging. Therefore, we aimed to evaluate whether phosphorylated tau181 (p-tau181) in plasma could be an accurate AD predictor.Methods: Participants from the ADNI database included 185 cognitively unimpaired subjects with negative Aβ (CU–), 66 subjects with pre-clinical AD (CU with positive Aβ), 164 subjects with mild cognitive impairment with negative Aβ (MCI–), 254 subjects with prodromal AD (MCI with positive Aβ), and 98 subjects with dementia. Multiple linear regression models, linear mixed-effects models, and local regression were used to explore cross-sectional and longitudinal associations of plasma p-tau181 with cognition, neuroimaging, or CSF biomarkers adjusted for age, sex, education, and APOE genotype. Besides, Kaplan–Meier and adjusted Cox-regression model were performed to predict the risk of progression to dementia. Receiver operating characteristic analyses were performed to evaluate the predictive value of p-tau181.Results: Plasma p-tau181 level was highest in AD dementia, followed by prodromal AD and pre-clinical AD. In pre-clinical AD, plasma p-tau181 was negatively associated with hippocampal volume (β = −0.031, p-value = 0.017). In prodromal AD, plasma p-tau181 was associated with decreased global cognition, executive function, memory, language, and visuospatial functioning (β range −0.119 to −0.273, p-value < 0.05) and correlated with hippocampal volume (β = −0.028, p-value < 0.005) and white matter hyperintensity volume (WMH) volume (β = 0.02, p-value = 0.01). In AD dementia, increased plasma p-tau181 was associated with worse memory. In the whole group, baseline plasma p-tau181 was significantly associated with longitudinal increases in multiple neuropsychological test z-scores and correlated with AD-related CSF biomarkers and hippocampal volume (p-value < 0.05). Meanwhile, CU or MCI with high plasma p-tau181 carried a higher risk of progression to dementia. The area under the curve (AUC) of the adjusted model (age, sex, education, APOE genotype, and plasma p-tau181) was 0.78; that of additionally included CSF biomarkers was 0.84.Conclusions: Plasma p-tau181 level is related to multiple AD-associated cognitive domains and AD-related CSF biomarkers at the clinical stages of AD. Moreover, plasma p-tau181 level is related to the change rates of cognitive decline and hippocampal atrophy. Thus, this study confirms the utility of plasma p-tau181 as a non-invasive biomarker for early detection and prediction of AD.

Complement factor B (CFB) variants have been described to play a causative role in auto-immune associated C3 glomerulopathy (C3G) and/or atypical hemolytic uremic syndrome (aHUS) by affecting the dysregulations of alternative pathway activation. However, CFB variant concomitant with COL4A5 variant is scarce. Here, we depict two intriguing cases with concurrent novel heterozygosity for CFB c.2054_2057del (p.Ser687Profs∗16) variant and a previous reported COL4A5 c.2999G > T (p.Gly1000Val) variant in a pair of siblings. The clinical feature of either paternal CFB variant or maternal COL4A5 variant is just mild microscopic hematuria. Interestingly, their two children with paternal CFB c.2054_2057del (p.Ser687Profs∗16) variant and maternal COL4A5 c.2999G > T (p.Gly1000Val) variant presented with massive proteinuria, hematuria, and progressive renal failure with poor treatment response. Moreover, complement pathway activation in renal tissue further supports and strengthens the pathogenic role of CFB variant in the development of renal injury in the presence of COL4A5 variant. In conclusion, the rare sibling cases highlight that the extension of genetic analyses in the proband is helpful for the diagnosis and understanding of some family cluster renal diseases.

Peroxisomes are ubiquitous organelles in eukaryotic cells that fulfill multiple important metabolisms. Pex13 and Pex14 are key components of the peroxisomal docking complex in yeasts and mammals. In the present work, we functionally characterized the homologues of Pex13 and Pex14 (Mopex13 and Mopex14) in the rice blast fungus Magnaporthe oryzae. Mopex13 and Mopex14 were peroxisomal membrane distributed and were both essential for the maintenance of Mopex14/17 on the peroxisomal membrane. Mopex13 and Mopex14 interacted with each other, and with Mopex14/17 and peroxisomal matrix protein receptors. Disruption of Mopex13 and Mopex14 resulted in a cytoplasmic distribution of peroxisomal matrix proteins and the Woronin body protein Hex1. In the ultrastructure of Δmopex13 and Δmopex14 cells, peroxisomes were detected on fewer occasions, and the Woronin bodies and related structures were dramatically affected. The Δmopex13 and Δmopex14 mutants were reduced in vegetative growth, conidial generation and mycelial melanization, in addition, Δmopex13 showed reduced conidial germination and appressorial formation and abnomal appressorial morphology. Both Δmopex13 and Δmopex14 were deficient in appressorial turgor and nonpathogenic to their hosts. The infection failures in Δmopex13 and Δmopex14 were also due to their reduced ability to degrade fatty acids and to endure reactive oxygen species and cell wall-disrupting compounds. Additionally, Mopex13 and Mopex14 were required for the sexual reproduction of the fungus. These data indicate that Mopex13 and Mopex14, as key components of the peroxisomal docking complex, are indispensable for peroxisomal biogenesis, fungal development and pathogenicity in the rice blast fungus.

Reliable dynamic mechanical properties of high nitrogen steels are necessary for the design and assessment of armor structures subject to impact and blast. A series of experiments, based on Hopkinson bar techniques, were conducted and described in this study. The dynamic compression, tensile and shear properties of high nitrogen steel had been tested, and the stress-strain curves under high strain rates were obtained. The results have been showed as follows: High nitrogen steel has a remarkable strain rate strengthening effect. Compared to the static curves, the constitutive curves of dynamic tension and compression move upper. The dynamic compressive yield strength of high nitrogen steel increases first and then decreases with the increase of strain rate, and the yield strength varies in the range of 1465–1549 MPa within the range of 1147–2042 s−1 strain rate; The tensile strength of high nitrogen steel increases with the increase of strain rate. When the strain rate is greater than 1341 s−1, the tensile strength will not increase and the curve tends to be gentle. The pure shear yield strength of the high nitrogen steel is above 800 MPa. Keywords: High nitrogen steels, Hopkinson bar, Dynamic compression, Dynamic tension, Dynamic shear

[This corrects the article DOI: 10.1371/journal.pone.0224635.].

Magnaporthe oryzae, a fungal pathogen that causes rice blast, which is the most destructive disease of rice worldwide, has the potential to perform both asexual and sexual reproduction. MAT loci, consisting of MAT genes, were deemed to determine the mating types of M. oryzae strains. However, investigation was rarely performed on the development and molecular mechanisms of the sexual reproduction of the fungus. In the present work, we analyzed the roles of two MAT loci and five individual MAT genes in the sex determination, sexual development and pathogenicity of M. oryzae. Both of the MAT1-1 and MAT1-2 loci are required for sex determination and the development of sexual structures. MAT1-1-1, MAT1-1-3 and MAT1-2-1 genes are crucial for the formation of perithecium. MAT1-1-2 impacts the generation of asci and ascospores, while MAT1-2-2 is dispensable for sexual development. A GFP fusion experiment indicated that the protein of MAT1-1-3 is distributed in the nucleus. However, all of the MAT loci or MAT genes are dispensable for vegetative growth, asexual reproduction, pathogenicity and pathogenicity-related developments of the fungus, suggesting that sexual reproduction is regulated relatively independently in the development of the fungus. The data and methods of this work may be helpful to further understand the life cycle and the variation of the fungus.

Maintenance of lipid homeostasis is crucial for cells in response to lipid requirements or surplus. The SREBP transcription factors play essential roles in regulating lipid metabolism and are associated with many metabolic diseases. However, SREBP regulation of lipid metabolism is still not completely understood. Here, we showed that reduction of SBP-1, the only homolog of SREBPs in Caenorhabditis elegans, surprisingly led to a high level of zinc. On the contrary, zinc reduction by mutation of sur-7, encoding a member of the cation diffusion facilitator (CDF) family, restored the fat accumulation and fatty acid profile of the sbp-1(ep79) mutant. Zinc reduction resulted in iron overload, which thereby directly activated the conversion activity of stearoyl-CoA desaturase (SCD), a main target of SREBP, to promote lipid biosynthesis and accumulation. However, zinc reduction reversely repressed SBP-1 nuclear translocation and further downregulated the transcription expression of SCD for compensation. Collectively, we revealed zinc-mediated regulation of the SREBP-SCD axis in lipid metabolism, distinct from the negative regulation of SREBP-1 or SREBP-2 by phosphatidylcholine or cholesterol, respectively, thereby providing novel insights into the regulation of lipid homeostasis.

Abstract Trachelospermum jasminoides is commonly used in traditional Chinese medicine. However, the use of the plant’s local alternatives is frequent, causing potential clinical problems. The T. jasminoides sold in the medicine market is commonly dried and sliced, making traditional identification methods difficult. In this study, the ITS2 region was evaluated on 127 sequences representing T. jasminoides and its local alternatives according to PCR and sequencing rates, intra- and inter-specific divergences, secondary structure, and discrimination capacity. Results indicated the 100% success rates of PCR and sequencing and the obvious presence of a barcoding gap. Results of BLAST 1, nearest distance and neighbor-joining tree methods showed that barcode ITS2 could successfully identify all the texted samples. The secondary structures of the ITS2 region provided another dimensionality for species identification. Two-dimensional images were obtained for better and easier identification. Previous studies on DNA barcoding concentrated more on the same family, genus, or species. However, an ideal barcode should be variable enough to identify closely related species. Meanwhile, the barcodes should also be conservative in identifying distantly related species. This study highlights the application of barcode ITS2 in solving practical problems in the distantly related local alternatives of medical plants.

Powdery mildew (PM), which is mainly caused by Podosphaera xanthii, is a serious biotrophic pathogen disease affecting field-grown and greenhouse-grown cucurbit crops worldwide. Because fungicides poorly control PM, the development and cultivation of PM-resistant varieties is critical. A homolog of SGT1 (suppressor of the G2 allele of skp1), which encodes a key component of the plant disease-associated signal transduction pathway, was previously identified through a transcriptomic analysis of a PM-resistant pumpkin (Cucurbita moschata) inbred line infected with PM. In this study, we have characterized this SGT1 homolog in C. moschata, and investigated its effects on biotic stress resistance. Subcellular localization results revealed that CmSGT1 is present in the nucleus. Additionally, CmSGT1 expression levels in the PM-resistant material was strongly induced by PM, salicylic acid (SA) and hydrogen peroxide (H2O2). In contrast, SA and H2O2 downregulated CmSGT1 expression in the PM-susceptible material. The ethephon (Eth) and methyl jasmonate (MeJA) treatments upregulated CmSGT1 expression in both plant materials. The constitutive overexpression of CmSGT1 in Nicotiana benthamiana (N. benthamiana) minimized the PM symptoms on the leaves of PM-infected seedlings, accelerated the onset of cell necrosis, and enhanced the accumulation of H2O2. Furthermore, the expression levels of PR1a and PR5, which are SA signaling transduction markers, were higher in the transgenic plants than in wild-type plants. Thus, the transgenic N. benthamiana plants were significantly more resistant to Erysiphe cichoracearum than the wild-type plants. This increased resistance was correlated with cell death, H2O2 accumulation, and upregulated expression of SA-dependent defense genes. However, the chlorosis and yellowing of plant materials and the concentration of bacteria at infection sites were greater in the transgenic N. benthamiana plants than in the wild-type plants in response to infections by the pathogens responsible for bacterial wilt and scab. Therefore, CmSGT1-overexpressing N. benthamiana plants were hypersensitive to these two diseases. The results of this study may represent valuable genetic information for the breeding of disease-resistant pumpkin varieties, and may also help to reveal the molecular mechanism underlying CmSGT1 functions.

Contamination control and removal are very important technical aspects of microbiological research. Bacterial contamination is very common in fungal cultures. Currently, the commonly used approach for inhibiting bacteria is antibiotic treatment; however, there are drawbacks to using antibiotics, including incomplete removal, limited antibacterial spectra, tendency toward recontamination, effects to fungal strains, and potential risks to the environment. Therefore, in the present work, we developed a new method for bacterial removal from fungi cultured on solid medium, the Cabin-Sequestering (CS) method, based on the different culture characteristics between fungi and bacteria. First, 3-5 mm round or square holes (the "cabin") are excavated on a solid medium plate. The fungal strain containing possible bacterial contamination is inoculated into the cabin. The cabin is then covered with a sterilized coverslip, followed by incubation at the appropriate temperature. After 7-10 days of culturing, fungal hyphae grow out along the edge of the coverslip; however, the contaminating bacteria cannot pass through the space formed between the medium and the coverslip and, thus, remain in the cabin. The newly grown fungal hyphae around the coverslip are re-inoculated into fresh culture plates, where they form bacteria-free fungal colonies. The CS method is easy handling, with a short experimental cycle and rare recontamination. When necessary, it can also be used in combination with antibiotics in bacterial removal operations.

Crataegi folium have been used as medicinal and food materials worldwide due to its pharmacological activities. Although the leaves of Crataegus songorica (CS), Crataegus altaica (CA) and Crataegus kansuensis (CK) have rich resources in Xinjiang, China, they can not provide insights into edible and medicinal aspects. Few reports are available on the qualitative and quantitative analysis of flavonoids compounds of their leaves. Therefore, it is necessary to develop efficient methods to determine qualitative and quantitative flavonoids compounds in leaves of CS, CA and CK. In the study, 28 unique compounds were identified in CS versus CK by qualitative analysis. The validated quantitative method was employed to determine the content of eight flavonoids of the leaves of CS, CA and CK within 6 min. The total content of eight flavonoids was 7.8–15.1 mg/g, 0.1–9.1 mg/g and 4.8–10.7 mg/g in the leaves of CS, CA and CK respectively. Besides, the best harvesting periods of the three species were from 17th to 26th September for CS, from 30th September to 15th October for CA and CK. The validated and time-saving method was successfully implemented for the analysis of the content of eight flavonoids compounds in CS, CA and CK for the first time.

The accurate identification and quality evaluation of herbal medical plants is highly necessary to ensure their safety and efficacy. In present study, a new strategy combining DNA barcoding techniques with thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) was proposed to facilitate the identification and quality control of M. tenacissima. In present work, the internal transcribed spacer 2 (ITS2) barcode was successfully used to identify 58 M. tenacissima samples and its adulterants. TLC successfully identified the other three M. tenacissima samples that failed to produce ITS2 regions. An adulterant was found in all the 62 samples. Moreover, the content of active medicinal ingredients is important for herbal plants quality. The content of tenacissoside H (TS-H) of M. tenacissima samples was determined by HPLC to range from 0.39% to 1.09%, which meets the criterion of the Chinese Pharmacopoeia. Thus, DNA barcoding coupled with TLC and HPLC is very promising to identify and evaluate the quality of M. tenacissima in the medicine market.

Nitrogen isotope (δ15N) has been employed to differentiate major sources of atmospheric N. However, it remains a challenge to quantify contributions of multiple sources based on δ15N values of the N mixture in atmospheric samples. This study measured δ15N of bulk N in PM2.5 at an urban site of Beijing during a severe haze episode of 22–30 January 2013 and a background site of Qinghai, north-western China from 6 September to 15 October 2013, then applied a Bayesian isotope mixing model (SIAR, Stable Isotope Analysis in R) to analyse the N sources. At Beijing site, δ15N values of PM2.5 (−4.1‰ to +13.5‰, +2.8 ± 6.4‰) were distributed within the range of major anthropogenic sources (including NH3 and NO2 from coal combustion, vehicle exhausts and domestic wastes/sewage). At Menyuan site, δ15N values of PM2.5 (+8.0‰ to +27.9‰, +18.5 ± 5.8‰) were significantly higher than that of potential sources (including NH3 and NO2 from biomass burning, animal wastes, soil N cycle, fertilizer application and dust N). High molar ratios of $ {\text{NH}}_4^{+} $ to $ {\text{NO}}_3^{-} $ and/or $ {\text{SO}}_4^{2-} $ in PM2.5 at the background site suggested that the equilibrium of NH3 ↔ $ {\text{NH}}_4^{+} $ caused apparent 15N enrichments in ammonium. Results of the SIAR model showed that 39 and 32% of bulk N in PM2.5 of Beijing site were contributed from N emissions of coal combustion and vehicle exhausts, respectively, whereas N in PM2.5 at Menyuan site was derived mainly from N emissions of biomass burning (46%) and NH3 volatilization (34%). These results revealed that the stoichiometry between NH3 and acidic gases plays an important role in controlling the bulk δ15N signatures of PM2.5 and emissions of reactive N from coal combustion and urban transportation should be strictly controlled to advert the risk of haze episodes in Beijing.

The growing burden of end-stage renal disease (ESRD) has been a great challenge to the health care system of China. However, the exact epidemiological data for ESRD in China remain unclear. We aimed to investigate the epidemiology of ESRD treated by renal replacement therapy (RRT) in Nanjing based on analysing ten-year data of Nanjing three million insurance covered population.Using the electronic registry system of Urban Employee Basic Medical Insurance (UEBMI), we included all subjects insured by UEBMI in Nanjing from 2005 to 2014 and identified subjects who developed ESRD and started RRT in this cohort.The UEBMI population in Nanjing increased from 1,301,882 in 2005 to 2,921,065 in 2014, among which a total of 5,840 subjects developed ESRD and received RRT. Over the 10-year period, the adjusted incidence rates of RRT in the UEBMI cohort gradually decreased from 289.3pmp in 2005 to 218.8pmp in 2014. However, the adjusted prevalence rate increased steadily from 891.7pmp in 2005 to 1,228.6pmp in 2014. The adjusted annual mortality rate decreased from 138.4 per 1000 patient-years in 2005 to 97.8 per 1000 patient-years in 2014. The long-term survival rate fluctuated over the past decade, with the 1-year survival rate ranging from 85.1% to 91.7%, the 3-year survival rate from 69.9% to 78.3% and the 5-year survival rate from 58% to 65.4%.Nanjing is facing an increasing burden of ESRD with its improvement of medical reform. The ten-year complete registry data on RRT in urban employees in Nanjing provided a unique opportunity to understand the real threat of ESRD confronting China during its process of health care transition.

To determine the safety and feasibility of intraductal radiofrequency ablation (RFA) followed by locoregional tumor treatments in patients with non-resectable malignant biliary obstruction and stent re-occlusion.Fourteen patients with malignant biliary obstruction and blocked metal stents were studied retrospectively. All had intraductal RFA followed by locoregional tumor treatments and were monitored clinically and radiologically. The practicality, safety, postoperative complications, jaundice remission, stent patency and survival time were analyzed.Combination treatment was successful for all patients. There were no severe complications during RFA or local treatments. All patients had stent patency restored, with a decline in serum bilirubin. Three patients had recurrent jaundice by 195, 237 and 357 days; two patients underwent repeat intraductal RFA; and one required an internal-external biliary drain. The average stent patency time was 234 days (range 187-544 days). With a median follow-up of 384 days (range 187-544 days), six patients were alive, while eight had died. There was no mortality at 30 days. The 3, 6, 12 and 18 month survival rates were 100%, 100%, 64.3% and 42.9%, respectively.Intraductal RFA followed by locoregional tumor treatments for occluded metal stents is safe and practically feasible and potential increase stent patency and survival times.

The effects of CO2 enrichment on growth and development of Impatiens hawkeri, an important greenhouse flower, were investigated for the purpose of providing scientific basis for CO2 enrichment to this species in greenhouse. The plants were grown in CO2-controlled growth chambers with 380 (the control) and 760 (CO2 enrichment) μmol⋅mol-1, respectively. The changes in morphology, physiology, biochemistry, and leaf ultrastructure of Impatiens were examined. Results showed that CO2 enrichment increased flower number and relative leaf area compared with the control. In addition, CO2 enrichment significantly enhanced photosynthetic rate, contents of soluble sugars and starch, activities of peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX), but reduced chlorophyll content and malondialdehyde (MDA) content. Furthermore, significant changes in chloroplast ultrastructure were observed at CO2 enrichment: an increased number of starch grains with an expanded size, and an increased ratio of stroma thylakoid to grana thylakoid. These results suggest that CO2 enrichment had positive effects on Impatiens, that is, it can improve the visual value, promote growth and development, and enhance antioxidant capacity.

Seed set is usually low and differs for different crosses of flower lotus (Nelumbo nucifera Gaertn.). The reasons remain unknown, and this has a negative impact on lotus breeding. To determine the causes, we carried out two crosses of flower lotus, that is, “Jinsenianhua” × “Qinhuaihuadeng” and “Qinhuaihuadeng” × “Jinsenianhua” and pollen viability, pistil receptivity, and embryo development were investigated. The pollen grains collected at 05:00-06:00 hrs had the highest viability, and the viabilities of “Jinsenianhua” and “Qinhuaihuadeng” were 20.6 and 15.7%, respectively. At 4 h after artificial pollination, the number of pollen grains germinating on each stigma reached a peak: 63.0 and 17.2 per stigma in “Jinsenianhua” × “Qinhuaihuadeng” and “Qinhuaihuadeng” × “Jinsenianhua”, respectively. At 1 d after artificial pollination, the percentages of normal embryos in the two crosses were 55.0 and 21.9%, respectively; however, at 11 d after pollination, the corresponding percentages were 20.8 and 11.2%. Seed sets of the two crosses were 17.9 and 8.0%, respectively. The results suggested that low pistil receptivity and embryo abortion caused low seed set in “Qinhuaihuadeng” × “Jinsenianhua”, whereas low fecundity of “Jinsenianhua” × “Qinhuaihuadeng” was mainly attributable to embryo abortion.

In the title compound, [Cu(C4H4O5)(C5H8N2)2(H2O)]·2H2O, the CuII cation assumes a distorted octahedral coordination geometry formed by two 3,5-dimethyl-1H-pyrazole ligands, one oxydiacetate (ODA) dianion and one coordinated water molecule. The tridentate ODA ligand chelates to the Cu cation in a facial configuration with a longer Cu—O bond [2.597 (3) Å], and both chelating rings display envelope conformations. In the molecule, the two pyrazole rings are twisted with respect to each other at a dihedral angle of 57.5 (3)°. Extensive intermolecular O—H...O and N—H...O hydrogen bonding is present in the crystal structure.

The title compound, [Zn(C7H3NO4)(C6H6N4S2)(H2O)]·4H2O, assumes a distorted octahedral coordination geometry around the Zn2+ cation, formed by a diaminobithiazole (DABT) molecule, a pyridine-2,6-dicarboxylate anion and a water molecule. The pyridine-2,6-dicarboxylate anion chelates to the ZnII atom with a facial configuration. Within the chelating DABT ligand, the two thiazole rings are twisted by a dihedral angle of 14.52 (8)° with respect to each other. O—H...O and N—H...O hydrogen bonds occur in the crystal structure.

In the title compound, [Ni(C4H4O4S)(C6H6N4S2)(H2O)]·H2O, the NiII cation assumes a distorted octahedral coordination geometry formed by a diaminobithiazole (DABT) ligand, a thiodiacetate (TDA) dianion and a coordinated water molecule. The tridentate TDA chelates to the Ni cation in a facial configuration, and both chelating rings display the envelope conformations. The two thiazole rings of the DABT ligand are twisted with respect to each other, making a dihedral angle of 9.96 (9)°. Extensive O—H...O, N—H...O and weak C—H...O hydrogen bonding is present in the crystal structure.

AIM: To explore the relationship of MMP-9 and serum fructosamine levels and further illustrate the role of the development in diabetic retinopathy patients.METHODS: Serum MMP-9 levels were measured using enzyme-linkedimmunosorbent assays a in 30 health controls and 30 diabetic retinopathy patients, the relationship of MMP-9 and serum fructosamine levels were analyzed。RESULTS: Compared with healthy controls. The expression levels of MMP-9 indiabetic retinopathy patients were significantly increased \〖(8.14±2.28pmol/L), vs(2.47±1.41pmol/L)\〗, MMP-9 were positive correlation with fructosamine(r=0.94, PCONCLUSION:The occurrence and progress of diabetic retinopathy might be closely related to the expression level of MMP-9, and the abnormal expression of MMP-9 in patients' serum might be associated with the secretion of fructosamine.

In the title compound, [Zn(C4H5O2)Cl(C6H6N4S2)]·H2O, the ZnII cation is coordinated by a bidentate diaminobithiazole (DABT) ligand, a but-2-enoate anion and a Cl− anion in a distorted tetrahedral geometry. Within the DABT ligand, the two thiazole rings are twisted to each other at a dihedral angle of 4.38 (10)°. An intramolecular N—H...O interaction occurs. The centroid–centroid distance of 3.6650 (17) Å and partially overlapped arrangement between nearly parallel thiazole rings of adjacent complexes indicate the existence of π–π stacking in the crystal structure. Extensive O—H...Cl, O—H...O, N—H...Cl and N—H...O hydrogen bonding helps to stabilize the crystal structure.

The results of several new clinical trials that compared the effectiveness of entecavir (ETV) treatment with that of adefovir (ADV) treatment in patients with chronic hepatitis B (CHB) were published in recent years. However, the numbers of patients included in these clinical trials were too small to draw a clear conclusion as to whether ETV is more effective than ADV. Therefore, a new meta-analysis was needed to compare ETV with ADV for the treatment of CHB. A search of the Cochrane Central Register of Controlled Trials (CCTR), MEDLINE, the Science Citation Index, Embase, the China National Knowledge Infrastructure (CNKI), and the Wanfang Database for relevant studies published between 1966 and 2010 was performed. Trials comparing the use of ETV and ADV for the treatment of CHB were assessed. Of the 2,358 studies screened, 13 randomized controlled clinical trials comprising 1,230 patients (ETV therapy, 621; ADV therapy, 609) were analyzed. The serum hepatitis B virus (HBV) DNA clearance rate obtained in patients treated with ETV was significantly higher than that in patients treated with ADV at the 24th and 48th weeks of treatment (24 weeks: 59.6% vs. 31.8%, relative risk [RR], 1.82, 95% CI: 1.49-2.23; 48 weeks: 78.3% vs. 50.4%, RR, 1.61, 95% CI: 1.32-1.96). The serum HBeAg clearance rate, the HBeAg seroconversion rate, and the ALT normalization rate obtained for patients treated with ETV were also higher than the corresponding values for patients treated with ADV at the 48th week of treatment. The safety profiles were similar between patients treated with ETV and those treated with ADV. The evidence reviewed in this meta-analysis suggests that patients with hepatitis B have a greater likelihood of achieving a viral response and a biomedical response when treated with ETV than when treated with ADV.