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QiHong Wu,1 RongRong Jin,2 Ting Feng,1 Li Liu,2 Li Yang,2 YuHong Tao,3 James M Anderson,4,5 Hua Ai,2,6 Hong Li1,3 1Key Laboratory of Obstetrics, Gynecology, Pediatric Disease, and Birth Defects, Ministry of Education, West China Second University Hospital, 2National Engineering Research Center for Biomaterials, 3Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China; 4Department of Biomedical Engineering, 5Department of Pathology, Case Western Reserve University, Cleveland, OH, US; 6Department of Radiology, West China Hospital, Sichuan University, Chengdu, China Abstract: Superparamagnetic iron oxide nanoparticles have been widely used in biomedical applications, but understanding of their interactions with the biological immune system is relatively limited. This work is focused on dextran-coated iron oxide nanoparticles and their induced autophagy in human monocytes. We found that these nanoparticles can be taken up by human monocytes, followed by localization within vesicles or free in cytoplasm. Autophagosome formation was observed with increased expression of LC3II protein, the specific marker of autophagy. The autophagy substrate p62 was degraded in a dose-dependent manner, and autophagy was blocked by autophagy (or lysosome) inhibitors alone or along with iron oxide nanoparticles, indicating that autophagosome accumulation was mainly due to autophagy induction, rather than blockade of autophagy flux. Interestingly, iron oxide nanoparticles increased the viability of human monocytes, but the mechanism was not clear. We further found that inhibition of autophagy mostly attenuated the survival of cells, with acceleration of the inflammation induced by these nanoparticles. Taken together, autophagic activation in human monocytes may play a protective role against the cytotoxicity of iron oxide nanoparticles. Keywords: autophagy, cytotoxicity, human monocytes, inflammation, iron oxide nanoparticles

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Here, we report the frequency-dependent spectrum of ice Ih in the range of 0.2-2 THz. We confirm the presence of a feature that blue-shifts from around 1.55-1.65 THz with a decreasing temperature from 260 to 160 K. There is also a change in the trend of the refractive index of ice corresponding to a dispersion, which is also around 1.6 THz. The features are reproduced in data acquired with three commercial terahertz time-domain spectrometers. Computer-simulated spectra assign the feature to lattice translations perpendicular to the 110 and 1̄10 planes of the ice Ih crystal. The feature's existence should be recognized in the terahertz measurements of frozen aqueous solution samples to avoid false interpretations., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Guanosine monophosphate (GMP) is a nucleotide that can self-assemble in aqueous solution under certain conditions. An understanding of the process at the molecular level is an essential step to comprehend the involvement of DNA substructures in transcription and replication, as well as their relationship to genetic diseases such as cancer. We present the temperature-dependent terahertz (1.5-12 THz, 50-400 cm -1 ) absorptivity spectra of aqueous Na 2 GMP solution in comparison with the aqueous solutions of other RNA nucleotides. Distinct absorption features were observed in the spectrum of GMP, which we attribute to the intramolecular modes of the self-assemblies (i.e., G-complexes) that, at 1 M, start to form at 313 K and below. Changes in broad-band features of the terahertz spectrum were also observed, which we associate with the release of hydration water in the temperature-dependent formation of guanine quadruplexes. Using a state-of-the-art THz calorimetry approach correlating spectroscopic to thermodynamic changes, we propose a molecular mechanism of hydrophilic hydration driving GMP self-assembly as a function of temperature. The free energy contribution of hydrophilic hydration is shown as a decisive factor in guanine-quadruplex formation. Our findings spotlight the role of hydration in the formation of macromolecular structures and suggest the potential of hydration tuning for regulating DNA transcription and replication., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Recently, populations of Chinese spiny frogs (Quasipaa spinosa), an important amphibian species in China, have decreased, mainly due to a disease caused by the gram-negative bacteria Proteus mirabilis. To elucidate the immune response of the frogs, this study aimed to identify novel candidate genes functionally associated with P. mirabilis infection-induced "rotting skin" disease. Chinese spiny frogs were infected with P. mirabilis, and the skin transcriptome was sequenced using the MGISEQ-2000 platform. A total of 233,965 unigenes were obtained by sequencing, of which 27.23 % were known genes. Screening of differentially expressed genes (DEGs) indicated 210 unigenes differentially expressed after P. mirabilis infection, of which 132 unigenes were up-regulated, and 78 unigenes were down-regulated. Using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, DEGs were identified as enriched in signal pathways, such as oxidative phosphorylation, apoptosis, and the Janus kinase-signal transducer and activator of transcription pathway. Of the DEGs, there was a significant upregulation of the colony stimulating factor 2 receptor beta common subunit, interleukin 2 receptor subunit gamma, cathelicidin antimicrobial peptide, interleukin-17 receptor E, receptor-interacting serine/threonine-protein kinase 3, and pulmonary surfactant-associated protein D immune genes following P. mirabilis infection. Conversely, scavenger receptor cysteine-rich domain-containing group B protein, tumor protein p53 inducible nuclear protein 2, suppressor of cytokine signaling 2, and metalloreductase STEAP3 were significantly downregulated. In conclusion, the first skin transcriptome database of Chinese spiny frogs was established, and several immune genes were identified to elucidate the pathogenic mechanism of "skin rot" in Chinese spiny frogs and other cultured frogs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In May 2022, cases of monkeypox were reported in non-monkeypox endemic countries such as Europe and the United States. As of 26 May, a cumulative total of 257 laboratory-confirmed cases and approximately 120 suspected cases had been reported to WHO from non-monkeypox endemic countries. This event immediately caused great concern and alarm to the WHO and national virologists. This paper aims to summarize the epidemiological and clinical features of previous monkeypox virus infections and the current local outbreaks in non-monkeypox endemic countries and propose countermeasures to control the current localized infections in non-monkeypox endemic areas as soon as possible. We reviewed the literature and websites related to monkeypox. We searched Google Scholar, PubMed, Web of Science, Embase, and African Journals Online using the medical subject terms "monkeypox", "monkeypox virus", "monkeypox outbreak", "non-monkeypox endemic areas", "clinical features", "epidemiology", "transmission", and "infection". We found that monkeypox is a zoonotic disease of forest animals that has occurred mainly in West and Central Africa since the first case was reported in the Congo in 1970, with occasional cases spreading to countries such as the United States and Europe. It is common among students, housekeepers, hunters, farmers and housewives. It is more common in males than females, occurs below middle age, and is more common in children under 10. The incubation period is 5 to 21 days, and the rash usually appears within 1 to 3 days after the onset of fever. Clinical manifestations include fever, rash, swollen lymph nodes, headache, muscle pain and unusual weakness. Most patients have mild symptoms that last from 2 to 4 weeks. The source of the sudden outbreak in Europe and the United States is currently unknown and occurs mostly in homosexuals who have sex with men (MSM). Outbreaks of monkeypox virus infection in non-monkeypox endemic areas have received widespread attention and focus. We believe that a scientific response to the transmission route of monkeypox virus and, where necessary, vaccination of high-risk groups against the monkeypox smallpox will control infection in non-monkeypox endemic areas.

Medical image classification is a novel technology that presents a new challenge. It is essential that pathological images are automatically and correctly classified to enable doctors to provide precise treatment. Convolutional neural networks have demonstrated their effectiveness in classifying images in deep learning, which may have dozens or hundreds of layers, to illustrate the relationship between them in terms of their different neural network features. Convolutional layers consisting of small kernels take weights as input and guide them through an activation function as output. The main advantage of using convolutional neural networks (CNNs) instead of traditional neural networks is that they reduce the model parameters for greater accuracy. However, many studies have simply been focused on finding the best CNN model and classification results from a single medical image classification. Therefore, we applied a common deep learning network model in an attempt to identify the best model framework by training and validating different model parameters to classify medical images. After conducting experiments on six publicly available databases of pathological images, including colorectal cancer tissue, chest X-rays, common skin lesions, diabetic retinopathy, pediatric chest X-ray, and breast ultrasound image datasets, we were able to confirm that the recognition accuracy of the Inception V3 method was significantly better than that of other existing deep learning models.

Background: There is no suitable scoring system that can be used to predict mortality in children with acute paraquat intoxication (APP)., Aim: To optimize a predictive scoring system for mortality in children with APP., Methods: A total of 113 children with APP from January 1, 2010 to January 1, 2020 were enrolled in this study. These patients were divided into survivors and non-survivors. We compared the clinical characteristics between the two groups and analyzed the independent prognostic risk factors. The survival rates of patients with different values of the pediatric critical illness score (PCIS) were assessed using kaplan-meier survival analysis. The best scoring system was established by using the area under the receiver operating characteristic curve analysis., Results: The overall mortality rate was 23.4%. All non-survivors died within 20 days; 48.1% (13/27) died within 3 days, and 70.3% (19/27) died within 7 days. Compared to survivors, the non-survivors were older, had higher white blood cell count, alanine aminotransferase (ALT), aspartate aminotransferase, serum creatinine, blood urea nitrogen, glucose, and pediatric early warning score, and had lower platelet count, albumin, Serum sodium (Na + ) and PCIS. ALT and PCIS were the independent prognostic risk factors for children with APP. The survival rate of children classified as extremely critical patients (100%) was lower than that of children classified as critical (60%) or noncritical (6.7%) patients. The specificity of ALT was high (96.51%), but the sensitivity was low (59.26%). The sensitivity and specificity of ALT combined with PCIS were high, 92.59% and 87.21%, respectively. The difference in mortality was significantly higher for ALT combined with PCIS (area under the receiver operating characteristic: 0.937; 95%CI: 0.875-0.974; P < 0.05)., Conclusion: In our study, ALT and PCIS were independent prognostic risk factors for children with APP. ALT combined with PCIS is an optimal predictive mortality scoring system for children with APP., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases among the elderly people. The T2DM increases the risk of cardio-cerebrovascular disease (CCD), and the main pathological change of the CCD is atherosclerosis (AS). Meanwhile, the carbonic anhydrases (CAs) are involved in the formation and progression of plaques in AS. However, the exact physiological mechanism of carbonic anhydrase III (CAIII) has not been clear yet, and there are also no correlation study between CAIII protein and T2DM with CCD. The 8-week old diabetic mice (db/db -/- mice) and wild-type mice (wt mice) were feed by a normal diet till 32 weeks, and detected the carotid artery vascular opening angle using the method of biomechanics; The changes of cerebral cortex and myocardium were watched by the ultrastructure, and the autophagy were observed by electron microscope; The tissue structure, inflammation and cell injury were observed by Hematoxylin and eosin (HE) staining; The apoptosis of cells were observed by TUNEL staining; The protein levels of CAIII, IL-17, p53 were detected by immunohistochemical and Western Blot, and the Beclin-1, LC3, NF-κB were detected by Western Blot. All statistical analysis is performed using PRISM software. Compared with wt mice, db/db -/- mice' carotid artery open angle increased significantly. Electron microscope results indicated that autophagy in db/db -/- mice cerebral cortex and heart tissue decreased and intracellular organelle ultrastructure were damaged. HE staining indicated that, db/db -/- mice' cerebral cortex and heart tissue stained lighter, inflammatory cells infiltration, cell edema were obvious, myocardial fibers were disorder, and myocardial cells showed different degrees of degeneration. Compared with wt mice, TUNEL staining showed that there was obviously increase in db/db -/- mice cortex and heart tissue cell apoptosis. The results of immunohistochemistry and Western Blot indicated that CAIII, Beclin-1 and LC3II/I expression levels conspicuously decreased in cortex and heart tissue of db/db -/- mice, and the expression level of IL-17, NF-κB and p53 obviously increased. The carotid artery' vascular stiffness was increased and which was probably related with formation of AS in diabetic mice. And the autophagy participated in the occurrence and development of diabetic CCD. CAIII protein might somehow be involved in the regulation of autophagy probably through affecting cell apoptosis and inflammation, but the underlying mechanism remains to be further studied., (© 2021. The Author(s).)

Nine undescribed acylphloroglucinol derivatives, oblatones A-I, along with three known ones, were isolated from Syzygium oblatum. Their structures were determined on the basis of extensive spectroscopic analysis, including NMR and MS data interpretation. Oblatones A and B possess an alkylated chromanone scaffold featuring a hemiketal moiety. Oblatones C and D are the first acylphloroglucinol derivatives with an α,β-unsaturated ketone lipid chain. Some of the isolates showed inhibitory effects on ATP citrate lyase in vitro. The binding mode of oblatone A was predicted by molecular docking., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: Type 2 diabetes mellitus (T2DM) can lead to brain dysfunction and a series of neurological complications. Previous research demonstrated that a novel palmitic acid (5-PAHSA) exerts effect on glucose tolerance and chronic inflammation. Autophagy was important in diabetic-related neurodegeneration. The aim of the present study was to investigate whether 5-PAHSA has specific therapeutic effects on neurological dysfunction in diabetics, particularly with regard to autophagy., Methods: 5-PAHSA was successfully synthesized according to a previously described protocol. We then carried out a series of in vitro and in vivo experiments using PC12 cells under diabetic conditions, and DB/DB mice, respectively. PC12 cells were treated with 5-PAHSA for 24 h, while mice were administered with 5-PAHSA for 30 days. At the end of each experiment, we analyzed glucolipid metabolism, autophagy, apoptosis, oxidative stress, cognition, and a range of inflammatory factors., Results: Although there was no significant improvement in glucose metabolism in mice administered with 5-PAHSA, ox-LDL decreased significantly following the administration of 5-PAHSA in serum of DB/DB mice (p < 0.0001). We also found that the phosphorylation of m-TOR and ULK-1 was suppressed in both PC12 cells and DB/DB mice following the administration of 5-PAHSA (p < 0.05 and p < 0.01), although increased levels of autophagy were only observed in vitro (p < 0.05). Following the administration of 5-PAHSA, the concentration of ROS decreased in PC12 cells and the levels of CRP increased in high-dose group of 5-PAHSA (p < 0.01). There were no significant changes in terms of apoptosis, other inflammatory factors, or cognition in DB/DB mice following the administration of 5-PAHSA., Conclusion: We found that 5-PAHSA can enhance autophagy in PC12 cells under diabetic conditions. Our data demonstrated that 5-PAHSA inhibits phosphorylation of the m-TOR-ULK1 pathway and suppressed oxidative stress in PC12 cells, and exerted influence on lipid metabolism in DB/DB mice., (© 2021 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Objective: To explore the risk factors of acute kidney injury (AKI) in patients with sepsis in intensive care unit (ICU)., Methods: The medical records of patients diagnosed with sepsis in ICU of West China Hospital of Sichuan University from March 2009 to June 2016 were retrospectively analyzed. Differences between AKI group and Non-AKI group in general data, background disease, ICU entry and exit dates, complications, laboratory data and other related data were analyzed through univariate and multivariate statistical methods., Results: A total of 2331 patients with sepsis were included in the study, including 626 patients in the AKI group and 1695 patients in the Non-AKI group. The multivariate logistic regression analysis revealed that age >40 yr. (odds ratio ( OR ) =2.752), diabetes ( OR =2.563), hypertension/coronary heart disease ( OR =1.851), chronic kidney disease ( OR =15.876), heart failure ( OR =2.295), acute respiratory distress syndrome ( OR =2.067), severe acute pancreatitis ( OR =2.725), hypotension ( OR =2.140), hypoproteinemia ( OR =1.596), lactic acidosis ( OR =2.164), organ failure>1 ( OR =4.480), WBC>10×10 9 L -1 ( OR =4.166), serum creatinine ( OR =4.401), PCT ( OR =1.816), Cys-C ( OR =7.046), mild anemia ( OR =2.107), moderate anemia ( OR =3.817), and severe anemia ( OR =6.091) were all independent risk factors of SA-AKI., Conclusion: Several risk factors are related to the occurrence of SA-AKI in the ICU. Early identification and monitoring of risk factors for SA-AKI and early prevention of AKI can improve the prognosis of sepsis patients., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Six complexes {(3-bdppmapy)(AuCl) 2 } n ( 1 - 6 ; 3-bdppmapy = N , N '-bis(diphenylphosphanylmethyl)-3-aminopyridine and tht = tetrahydrothiophene) were simultaneously formed by the reaction of Au(tht)Cl and 3-bdppmapy in CH 2 Cl 2 followed by infusion with hexane. Complexes 4 - 6 could be produced independently by volatilizing solvent in air, solid-state heating, or solvothermal reaction. The PPh 2 -Au-Cl moieties extended in different directions, forming Au-Au and Au-Au-Au interactions. Complex 4 could be converted to 5 by heating to 130 °C, with the cleavage of one Au-Au bond, while 5 reverted back to 4 upon exposure to CH 2 Cl 2 vapor over 11 h. This solid-state phase transition could be recycled and was accompanied by a change in solid-state fluorescence, without obvious intensity decay over five cycles. The reason for both the phase transition and difference in photoluminescence is related to the different numbers and strengths of aurophilic interactions in each complex that could be modeled by density functional theory calculations.

In this article, we survey various non-contact, non-destructive testing methods by way of terahertz (THz) spectroscopy and imaging designed for use in various industrial sectors. A brief overview of the working principles of THz spectroscopy and imaging is provided, followed by a survey of selected applications from three industries-the building and construction industry, the energy and power industry, and the manufacturing industry. Material characterization, thickness measurement, and defect/corrosion assessment are demonstrated through the examples presented. The article concludes with a discussion of novel spectroscopy and imaging devices and techniques that are expected to accelerate industry adoption of THz systems.

To assess whether EGb761 could protect elderly diabetic mice with cognitive disorders and explore the role of beclin-1-mediated autophagy in these protective effects. Two-month-old male db/db -/- mice and wild-type C57/BL6 mice were randomly divided into six groups: db/db -/- control, db/db -/- 50 mg, db/db -/- 100 mg, wild-type (WT) control, WT 50 mg, and WT 100 mg. EGb761 (50 mg/kg or 100 mg/kg of bodyweight) was given by gavage once a day for 1 month from the age of 6 months. Y-maze and social choice tests were performed at 8th months. The blood pressure was measured. The imaging changes in the brain were measured using magnetic resonance imaging (MRI). The expression and distribution of beclin-1, LC3, and NF-κB were detected using immunohistochemistry staining and western blotting. Ultrastructure alterations in the hippocampus were observed using transmission electron microscopy. Compared with WT mice, the learning ability, memory and overall cognitive function of db/db -/- mice decreased (P < 0.05), and EGb761 could significantly improve the learning and memory function of db/db -/- mice (P < 0.05). EGb761 significantly improved systolic blood pressure in db/db -/- mice (P < 0.01). In addition, fMRI-bold showed a decline in the hippocampus of mice in the db/db -/- group compared with WT. EGb761 could improve these above changes. Immunohistochemistry staining and western blotting confirmed that EGb761 significantly increased beclin-1 and reduced LC3-II/I levels in the brains of db/db -/- mice (P < 0.05). NF-κB levels were obviously higher in the db/db -/- group than that in the WT group, and EGb761 significantly reduced NF-κB levels in db/db -/- mice (P < 0.05). There was a trend of increased autophagosomes in db/db -/- mice, but EGb761 did not change obviously the number of autophagosomes. Compared with normal aged WT mice, aging db/db -/- mice had more common complications of cerebral small vessel disease and cognitive dysfunction. EGb761 could significantly improve the cognitive function of aging db/db -/- mice via a mechanism that may involve the regulation of beclin-1, LC3, and NF-κB.

Nephronophthisis is an autosomal recessive cystic kidney disease and one of the most common genetic disorders causing end-stage renal disease in children. Nephronophthisis is a genetically heterogenous disorder with more than 25 identified genes. In 10%-20% of cases, there are additional features of a ciliopathy syndrome, such as retinal defects, liver fibrosis, skeletal abnormalities, and brain developmental disorders. This review provides an update of the recent advances in the clinical features and related gene mutations of nephronophthisis, and novel approaches for therapy in nephronophthisis patients may be needed., (© 2018 The Authors Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Background: The mechanism of podocyte apoptosis is not fully understood. In addition, the role of the inositol 1,4,5-triphosphate receptor (IP 3 R)/glucose-regulated protein 75 (Grp75)/voltage-dependent anion channel 1 (VDAC1)/mitochondrial calcium uniporter (MCU) calcium regulation axis, which is located at sites of endoplasmic reticulum (ER) mitochondria coupling, in the mechanism of podocyte apoptosis is unclear. This study aimed to understand the roles of this axis in podocyte apoptosis and explore potential targets for podocyte protection., Methods: The expression of IP 3 R, Grp75, VDAC1, and MCU and mitochondrial Ca 2+ were analyzed during Adriamycin- or angiotensin II-induced apoptosis in cultured mouse podocytes. The interaction between IP 3 R, Grp75, and VDAC1 was investigated using co-immunoprecipitation experiments. The effects of IP 3 R, Grp75, and MCU agonists and antagonists on mitochondrial Ca 2+ and apoptosis were investigated in cultured podocytes. The podocyte-protective effects of an MCU inhibitor were further investigated in rats with Adriamycin-induced nephropathy., Results: Increased expression of IP 3 R, Grp75, VDAC1 and MCU, enhanced interaction among the IP 3 R-Grp75-VDAC1 complex, mitochondrial Ca 2+ overload, and increased active caspase-3 levels were confirmed during Adriamycin- or angiotensin II-induced mouse podocyte apoptosis. Agonists of this axis facilitated mitochondrial Ca 2+ overload and podocyte apoptosis, whereas specific antagonists against IP 3 R, Grp75, or MCU prevented mitochondrial Ca 2+ overload and podocyte apoptosis. A specific MCU inhibitor prevented Adriamycin-induced proteinuria and podocyte foot process effacement in rats., Conclusions: This study identified a novel pathway in which the IP 3 R-Grp75-VDAC1-MCU calcium regulation axis mediated podocyte apoptosis by facilitating mitochondrial Ca 2+ overload. Antagonists that inhibit Ca 2+ transfer from ER to mitochondria protected mouse podocytes from apoptosis. An MCU inhibitor protected podocytes and decreased proteinuria in rats with Adriamycin-induced nephropathy. Therefore, antagonists to this pathway have promise as novel podocyte-protective drugs.

We study unextendible maximally entangled bases (UMEBs) in [Formula: see text] (d < d'). An operational method to construct UMEBs containing d(d' - 1) maximally entangled vectors is established, and two UMEBs in [Formula: see text] and [Formula: see text] are given as examples. Furthermore, a systematic way of constructing UMEBs containing d(d' - r) maximally entangled vectors in [Formula: see text] is presented for r = 1, 2, …, d - 1. Correspondingly, two UMEBs in [Formula: see text] are obtained.

The aim of the present study was to elucidate the effects of blocking the calcium signaling pathway of astrocytes (ASs) on oxygen and glucose deprivation (OGD)‑induced AS injury. The association between the changes in the concentrations of AS‑derived transmitter ATP and glutamic acid, and the changes in calcium signaling under the challenge of OGD were investigated. The cortical ASs of Sprague Dawley rats were cultured to establish the OGD models of ASs. The extracellular concentrations of ATP and glutamic acid in the normal group and the OGD group were detected, and the intracellular concentration of calcium ions (Ca2+) was detected. The effects of 2'‑deoxy‑N6‑methyl adenosine 3', 5'‑diphosphate diammonium salt (MRS2179), a P2Y1 receptor antagonist, on the release of calcium and glutamic acid of ASs under the condition of OGD were observed. The OGD challenge induced the release of glutamic acid and ATP by ASs in a time‑dependent manner, whereas elevation in the concentration of glutamic acid lagged behind that of the ATP and Ca2+. The concentration of Ca2+ inside ASs peaked 16 h after OGD, following which the concentration of Ca2+ was decreased. The effects of elevated release of glutamic acid by ASs when challenged by OGD may be blocked by MRS2179, a P2Y1 receptor antagonist. Furthermore, MRS2179 may significantly mitigate OGD‑induced AS injury and increase cell survival. The ASs of rats cultured in vitro expressed P2Y1 receptors, which may inhibit excessive elevation in the concentration of intracellular Ca2+. Avoidance of intracellular calcium overload and the excessive release of glutamic acid may be an important reason why MRS2179 mitigates OGD‑induced AS injury.

By studying the relationship between syndromes, physique and MMP-9, IL-6 and MTHFR gene polymorphisms in patients with ischemic stroke,The relationship between MMP-9, IL-6 and MTHFR gene polymorphism was analyzed in patients with ischemic stroke.The data were collected by collecting the data of patients with ischemic stroke, and the statistical analysis was carried out. Syndrome：61 cases of ischemic stroke patients with stroke phlegm stasis syndrome in patients with the highest frequency, a total of 30 cases; Physical constitution： phlegm is ischemic stroke patients prone to physical, a total of 20 cases; The analysis of the relationship between constitution and syndrome shows that the patients with qi deficiency constitution tend to show qi deficiency and blood stasis syndrome after onset, The analysis of the relationship between constitution and syndrome shows that the patients with qi deficiency constitution tend to show qi deficiency and blood stasis syndrome after onset, Phlegm constitution and physical condition after the onset of symptoms tend to wind phlegm stasis syndrome; Syndrome and MMP-9, IL-6 relationship：The distribution of MMP-9 and IL-6 in patients with qi and phlegm stasis syndrome and qi deficiency and blood stasis syndrome was significantly different from that in Z test (P<0.05). The level of MMP-9 in patients with qi deficiency and blood stasis syndrome was significantly higher than that in patients with wind phlegm and blood stasis syndrome;The level of IL-6 in patients with phlegm and blood stasis syndrome was significantly higher than that in patients with qi deficiency and blood stasis syndrome. Syndrome, constitution and MTHFR gene polymorphism： among the 61 samples, 34 were heterozygous mutations, 15 were pure and mutated, 12 had no mutation, The mutation rate of this locus was 4.08 times that of patients without mutations.The genotype of MTHFR C677T in patients with phlegm dampness tends to be CT genotype. Wind phlegm stasis syndrome in patients with easy to appear after the TT genotype; Yin deficiency syndrome in patients prone to miscellaneous and mutations, the performance of CT genotype; Analysis of the relationship between syndromes and physique in patients with ischemic stroke,Phlegm and dampness, flat quality patients after the onset of easy to show the wind phlegm stasis syndrome; Qi deficiency after the onset of symptoms in patients with Qi and blood stasis. Suggesting that before the onset of such as for the partial physical conditioning, may be on the prevention of ischemic stroke have a certain effect; Analysis of the relationship between syndromes and MMP-9 and IL-6 in patients with ischemic stroke, Wind phlegm stasis syndrome and IL-6 levels are related, Qi deficiency and blood stasis syndrome and MMP-9 levels are related. Analysis of the relationship between syndromes and MTHFR gene polymorphism in patients with ischemic stroke, TT genotype after the onset of symptoms prone to wind phlegm stasis syndrome, CT genotype patients after the onset of easy manifestations of Yin deficiency wind syndrome; Analysis of the relationship between physique and MTHFR gene polymorphism in patients with ischemic stroke, CT genotype is easy to show phlegm.For more in-depth understanding of pathogenesis of ischemic stroke to provide the basis, For the clinical treatment and prevention to provide intervention strategies., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Aims: Although cognitive dysfunction is a common neurological complication in elderly patients with diabetes, the mechanisms underlying this relationship remain unclear, and effective preventive interventions have yet to be developed. Thus, this study investigated the preventive effects and mechanisms of action associated with granulocyte colony-stimulating factor (G-CSF) on cognitive dysfunction in elderly diabetic mice with cerebral small vessel disease., Methods: This study included 40 male db/db diabetic and wild-type (WT) mice that were categorized into the following four groups at the age of 3 weeks: db/db group (DG), db/db+G-CSF group (DGG), WT group (WG), and WT+G-CSF group (WGG). The mice were fed normal diets for 4 months and then given G-CSF (75 μg/kg) via intraperitoneal injections for 1 month. At 7.5 months of age, the cognitive abilities of the mice were assessed with the Y-maze test and the Social Choice Test; body weight, blood pressure (BP), and blood glucose measurements were obtained throughout the study. Brain imaging and blood oxygen level-dependent (BOLD) contrast imaging analyses were performed with a small animal magnetic resonance imaging (MRI) system, autophagosome levels were detected with a transmission electron microscope (TEM), hippocampal neurons were assessed with hematoxylin and eosin (HE) staining, and protein expressions and distributions were evaluated using immunohistochemistry and Western blot analyses., Results: (i) The body weight and blood glucose levels of the DG and DGG mice were significantly higher than those of the WG and WGG mice; (ii) social choice and spatial memory capabilities were significantly reduced in DG mice but were recovered by G-CSF in DGG mice; (iii) the MRI scans revealed multiple lacunar lesions and apparent hippocampal atrophy in the brains of DG mice, but G-CSF reduced the number of lacunar lesions and ameliorated hippocampal atrophy; (iv) the MRI-BOLD scans showed a downward trend in whole-brain activity and reductions in the connectivities of the hippocampus and amygdala with subcortical structures in DG mice, but G-CSF clearly improved the altered brain activity as well as the connectivity of the hippocampus in DGG mice; (v) HE staining revealed fewer neurons in the hippocampus in DG mice; (vi) TEM analyses revealed significantly fewer autophagosomes in the hippocampi of DG mice, but G-CSF did not increase these numbers; (vii) there were significant reductions in mechanistic target of rapamycin (mTOR) and LC3-phosphatidylethanolamine conjugate (LC3)-II/I levels in the hippocampi of DG mice, whereas p62 was upregulated, and G-CSF significantly enhanced the levels of Beclin1, mTOR, and LC-II/I in DGG mice; and (viii) G-CSF significantly reversed increases in nuclear factor κB (NF-κB) protein levels in DG but not in WG mice., Conclusions: In this study, aged diabetic mice were prone to cognitive dysfunction and cerebral small vessel disease. However, administration of G-CSF significantly improved cognitive function in elderly db/db diabetic mice, and this change was likely related to the regulation of autophagy and NF-κB signaling pathways., (© 2017 John Wiley & Sons Ltd.)

Aim: We performed a meta-analysis of randomized controlled trials (RCT) and observational studies to answer the two following questions: (i) whether low maternal circulating 25 hydroxyvitamin D (25-OHD) is associated with an increased risk of preterm birth (PTB) or spontaneous PTB (sPTB); and (ii) whether vitamin D supplementation alone during pregnancy can reduce the risk of PTB., Methods: Literature search was carried out using Pubmed, Web of Science and Embase databases up to June 2016. Pooled OR or relative risk (RR) with 95%CI were computed using fixed or random effects models depending on the size of heterogeneity. Subgroup analysis was used to explore potential sources of between-study heterogeneity. Publication bias was evaluated using Egger's test and Begg's test., Results: Twenty-four articles (six RCT and 18 observational studies) were identified. Maternal circulating 25-OHD deficiency (pooled OR, 1.25; 95%CI: 1.13-1.38) rather than insufficiency (pooled OR, 1.09; 95%CI: 0.89-1.35) was associated with an increased risk of PTB, and vitamin D supplementation alone during pregnancy could reduce the risk of PTB (pooled RR, 0.57; 95%CI: 0.36-0.91). This was also the case for the sPTB subgroup (circulating 25-OHD <50 vs >50 nmol/L; pooled OR, 1.45; 95%CI: 1.20-1.75)., Conclusions: Maternal circulating 25-OHD deficiency could increase PTB risk and vitamin D supplementation alone during pregnancy could reduce PTB risk. Extrapolation of the results, however, must be done with caution, and there is urgent need for larger, better-designed RCT to confirm this effect., (© 2017 Japan Society of Obstetrics and Gynecology.)

Background: The evidence literature suggests that physical therapy practitioners are subjected to a high probability of acquiring work-related injuries, but only a few studies have specifically investigated Taiwanese physical therapy practitioners., Objective: This study was conducted to determine the relationships among individual and group hospital-level factors that contribute to the medical expenses for the occupational injuries of physical therapy practitioners in Taiwan., Participants: Physical therapy practitioners in Taiwan with occupational injuries were selected from the 2013 National Health Insurance Research Databases (NHIRD)., Methods: The age, gender, job title, hospitals attributes, and outpatient data of physical therapy practitioners who sustained an occupational injury in 2013 were obtained with SAS 9.3. SPSS 20.0 and HLM 7.01 were used to conduct descriptive and hierarchical linear model analyses, respectively., Results: The job title of physical therapy practitioners at the individual level and the hospital type at the group level exert positive effects on per person medical expenses. Hospital hierarchy moderates the individual-level relationships of age and job title with the per person medical expenses., Conclusion: Considering that age, job title, and hospital hierarchy affect medical expenses for the occupational injuries of physical therapy practitioners, we suggest strengthening related safety education and training and elevating the self-awareness of the risk of occupational injuries of physical therapy practitioners to reduce and prevent the occurrence of such injuries.

Tuina is a traditional Chinese treatment for sensory disturbances caused by peripheral nerve injury and related diseases. Our previous studies showed that tuina regulates relevant regions and indices of the spinal dorsal horn using the Dian , Bo , and Rou method in Yinmen (BL37), Yanglingquan (GB34), and Weizhong (BL40). Treatment prevents muscle atrophy, protects spinal cord neurons, and promotes sciatic nerve repair. The mechanisms of action of tuina for treating peripheral nerve injury remain poorly understood. This study established rat models of sciatic nerve injury using the crushing method. Rats received Chinese tuina in accordance with the principle of "Three Methods and Three Points," once daily for 20 days. Tuina intervention reduced paw withdrawal latency and improved wet weight of the gastrocnemius muscle, as well as promoting morphological recovery of sciatic nerve fibers, Schwann cells, and axons. The protein expression levels of phospho-p38 mitogen-activated protein kinase, tumor necrosis factor-α, and interleukin-1β also decreased. These findings indicate that "Three Methods and Three Points" promoted morphological recovery and improved behavior of rats with peripheral nerve injury., Competing Interests: Conflicts of Interest: None declared.

Forty batches of Lonicerae Japonica Fse i collected extensively and prepared as the test solution. Their chromatographic fingerprints and anti-influenza virus IC50 value (half maximal inhibitory concentration) were determined respectively. Then Unscrambler software was used, and spectrum-efficient correlation analysis was done for chromatographic fingerprints data and IC50 data by partial least squares regression method, to establish spectrum-efficient correlation model for anti-influenza virus of Lonicerae Japonicae Flos. Then the other 10 batches of Lonicerae Japonicae Flos were used to verify the model and explore the adaptability of this spectrum-efficient correlation model based on partial least squares regression method. The mathematical model obtained R2 of 0.969489 and RM-SEC of 0.070691 for calibration set; R2 of 0.959042 and RMSECV of 0.084005 for cross validation set. The verification experiment results showed that the relative error between the predicted values and measured values was within 10% in all 10 hatches, and within 5% in 80% of them. The results showed that the established spectrum-efficient correlation model could be used to evaluate the biological activity of anti-influenza virus of Lonicerae Japonicae Flos by determining its HPLC fingerprints.

Objective: Cryptococcus neoformans is a common opportunistic infection in adults with acquired immunodeficiency syndrome. However, limited data exist for pediatric patients. The aim of this study was to describe the clinical characteristics of cryptococcosis in pediatric patients., Patients and Methods: A retrospective study was conducted at West China Second University Hospital, Sichuan University. Data on risk factors, clinical manifestations, diagnosis methods, treatment, and prognosis were evaluated. Clinical characteristics associated with cryptococcal meningitis and disseminated cryptococcosis were compared., Results: Twelve cases of cryptococcal meningitis and 11 cases of disseminated cryptococcosis were identified. Seventeen cases had no underlying disease, but 6 cases had malnutrition. Only 6 cases had a history of exposure to pigeon droppings. No cases had pulmonary cryptococcosis alone. Coughing, pulmonary moist rales, swollen lymph nodes, liver and spleen, and skin rashes were seen only in disseminated cryptococcosis. The prevalence of headache and positive meningeal irritation sign was higher in cryptococcal meningitis than disseminated cryptococcosis. The proportion of increase in eosinophils was higher in disseminated cryptococcosis than cryptococcal meningitis. The primary methods used for diagnosis included cerebrospinal fluid ink staining, cerebrospinal fluid culture, blood culture, and lymph node biopsy. Two patients stopped treatment, and 21 patients received antifungal therapy. The mortality rate was 39.13%., Conclusions: Cryptococcosis occurs in non-HIV infected and immunocompetent children. Cryptococcosis lacks specific clinical manifestations. Disseminated cryptococcosis commonly occurs in children. Clinicians should consider a diagnosis of disseminated cryptococcosis for children who present with unexplained long-term fever, mild cough, chest imaging inconsistent with clinical symptoms, lymphadenectasis, hepatosplenomegaly, and eosinophilia.

Objective: To study the relationship between the suppression of the hypothalamic-pituitary-gonadal axis (HPGA) and the predicted adult height (PAH) in girls with central precocious puberty (CPP) during the treatment with gonadotropin-releasing hormone analogue (GnRHa), in order to provide guidance for individualized GnRHa dose adjustment in clinical practice., Methods: The clinical data of 75 CPP girls were collected, and then height, bone age (BA), uterine and ovarian volumes, and peak luteinizing hormone (LH), peak follicle-stimulating hormone (FSH), and estradiol (E2) levels were recorded at different time points of GnRHa treatment. PAH at each time point was calculated. PAH improvement (ΔPAH=PAH-target height) and its relationship with the degree of HPGA suppression were analyzed. Threshold effect analysis was applied to determine the best HPGA suppression range forΔPAH., Results: After GnRHa treatment, PAHs were improved markedly compared with the data in the early stage of treatment. ΔPAH showed a negative correlation with ΔBA. At 24 months of treatment, ΔPAH was also negatively correlated with LH. Uterine volume controlled between 2.3 and 3.0 mL, LH level controlled below 0.8 IU/L, and FSH controlled below 2.4 IU/L could slow down the growth of BA and improve PAH., Conclusions: GnRHa treatment can improve the PAH of CPP girls. Selection of an appropriate therapeutic dose for GnRHa to control uterine volume, LH and FSH levels within certain ranges can slow down the growth of BA and improve PAH.

Background: Central precocious puberty (CPP) is characterized as increasing gonadotropin-releasing hormone (GnRH) release. Orexin-A has also been shown to affect GnRH release. However, there are few reports about the effect of orexin A on the treatment of CPP., Methods: After establishing the precocious puberty model, the rats were divided into four groups: normal control, precocious puberty rats, precocious puberty rats treated with normal saline and precocious puberty rats treated with orexin-A. The vaginal opening time, second estrus cycle, ovarian index and uterus index of rats in each group were detected. qRT-PCR was performed to examine the expression of MEG3 and kisspeptin in rats. HT22 cells were transfected with pcDNA-MEG3 to detect the expression of Kisspeptin., Results: In this study, we found that orexin-A not only delayed the day of vaginal opening and regular estrus cycle days but also decreased the ovarian index and uterus index in rats with CPP. In addition, orexin-A reversed the up-regulation of MEG3 and kisspeptin in rats with CPP. In HT22 cells, the mRNA and protein level of kisspeptin were enhanced by pcDNA-MEG3., Conclusion: Our results suggest that orexin-A ameliorates central precocious puberty in rat and MEG3 might be involved in this effect, suggesting that MEG3 might be a novel target in treating central precocious puberty.

To breed a new yam cultivar of Dioscorea alata, the different and excellent germplasm resources were investigated within artificially cultivated population and some superior individuals, with a higher yield and medicinal properties, were selected. Considering results of the yield and medicinal properties during 2006-2013 cropping season, strains and lines were established and selected. As a result, the yield of the new developed cultivar (Wenshanyao No. 1, WSY01-1) reached 2217. 0 kg per 667 m2 (fresh weight) and 348.3 kg per 667 m2 (dry weight), and increased 23.8% and 23.9% comparing with control cultivars (landraces). Comparing with control cultivars, the level of polysaccharide, allantoin, and dioscin increased 36.9%, 48.3%, 20.9%, and reached 12.2%, 1.30%, 579.7 µg · g(-1), respectively. This result showed that the systematic selection method can significantly improve yield and medicinal properties of D. alata, and the developed " Wenshanyao No. 1" exhibits wide spreading prospects.

Objective: To explore the role of heparanase in the pathogenesis of respiratory syncytial virus (RSV) nephropathy in rats model., Methods: Twenty 150-200 g Sprague-Dawley (SD) rats (n = 5 per group) were inoculated with 6 x 10(6) PFU RSV and sacrificed on days 4, 8, 14 and 28 postinoculation (RSV4, RSV8, RSV14 and RSV29). Five SD rats inoculated with Dulbecco's minimum essential medium were served as normal control. The expression levels of heparanase protein and mRNA in the rat renal tissue of each group were determined by immunohistochemical staining and real-time quantitative RT-PCR respectively. The proteinurina was also measured and then the relationship between the expression level of heparanase and the 24-hour urinary protein was studied., Results: The rats with RSV nephropathy exhibited higher proteinuria in comparison with normal rats, and the 24-hour urinary protein level was significantly different between each RSV nephropathy group (RSV14 > RSV8 > RSV28 > RSV4, P < 0.05). Compared with normal control, the rats with RSV nephropathy showed up-regulated expression of heparanase protein in glomeruli. The expression levels of heparanase protein in RSV8 and RSV14 group were higher than those in RSV4 and RSV28 group (P < 0.05). There was a linear positive correlation between the expression level of glomerular heparanase protein and the quantity of 24-hour urinary protein (r = 0.783, P < 0.05). Compared with normal control group, the expression levels of heparanase mRNA in the kidney from RSV4, RSV8, RSV14, and RSV28 group were elevated (RSV14 > RSV8 > RSV4 > RSV28 , P < 0.05). There was a linear positive correlation between the expression level of renal heparanase mRNA and the quantity of 24-hour urinary protein (r = 0.725, P < 0.05)., Conclusion: The increased expression of heparanase in kidney may be important to the loss of glomerular negative charge in glomerular basement membrane which is involved in the pathogenesis of RSV nephropathy in rats.

Objective: Most of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug eruptions. There is currently no established treatment due to a lack of controlled/blinded studies. High-dose glucocorticoids and intravenous immunoglobulins (IVIG) therapy have been widely used, but these approaches remain controversial. This study introduces a novel method by which to treat severe SJS/TEN patients who were refractory to glucocorticoids and IVIG., Patients and Methods: Seven patients with SJS and three patients with TEN were enrolled in this non-blinded, uncontrolled study. The average patient age was 8.1 years. The male to female ratio was 1:1. Hemoperfusion was conducted daily using a HA280 resin sorbent column until new skin lesions ceased appearing and the skin started healing with visible re-epithelialization., Results: The average BSA involvement in SJS and TEN was 8.57% and 75%, respectively. The number of hemoperfusion sessions ranged from 3 to 5. Hemoperfusion led to prompt improvements in general health and halted the disease progression. All children were discharged and recovered completely. The average length of stay was 14.4 days. Four patients experienced adverse reactions: femoral vein thrombosis (N = 2), hypotension (N = 1), and cardiac palpitation (N = 1)., Conclusions: Hemoperfusion may be a useful adjunct treatment for patients with severe SJS/TEN if the initial treatment with glucocorticoids and IVIG fails.

Objective: To observe the proteome changes in the hippocampus tissue of rats with chronic Toxoplasma gondii infection., Methods: Six male SD rats were randomly divided into control group and infection group. Each rat in infection group was intraperitoneally injected with 4 x 10(7) purified T. gondii tachyzoites. Rats in the control group received equivalent volumes of sterile normal saline. At the fifth day post-infection, blood samples were taken from the lateral tail vein and Ciemsa staining of blood cells was performed to find Toxoplasma gondii. Rats were dissected at the 10th week post-infection, total protein in the hippocampus was separated by using two-dimensional gel electrophoresis (2-DE). After Coomassie blue staining, the Image Analysis software was used to select and separate proteins on the gel. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was used for peptide mass fingerprint PMF). Proteins were identified by using Mascot software to search the MSDB and SwissProt databases., Results: Microscopy examination of blood smears confirmed that the rats in infection group were all infected by 11 gondii. The number of protein spots of rats from infection group and control group was 311 +/- 19 and 327 +/- 13 respectively. Compared with the control group, 5 protein spots disappeared, 4 protein spots were up-regulated and 7 were down-regulated in the infection group. The 9 differentially expressed protein spots were identified by MALDL-TOF-MS: phosphoglycerate kinase 1, similar to alpha-enolase, glutamine synthetase, creatine kinase, creatine kinase B-type, ATP synthase, aconitase 2, mitochondrial precursor, actin and an unnamed protein. The first three proteins were up-regulated and the other five proteins were down-regulated in infection group., Conclusion: Nine differential expression proteins are found from the hippocampus tissue in rats chronically infected with T. gondii and normal SD rats.

Objective: To establish an easy and feasible method for primary culture and identification of rat glomerular podocytes., Methods: Glomeruli from Sprague-Dawley (SD) rats weighing 60-100 gram were isolated by the method of different size combination of screen. Isolated glomeruli were appropriately digested with 2 g/L type IV collagenase and cultured in 25 cm2 plastic flask coated with rat tail collagen in K1-3T3 medium with ITS-X (containing insulin-transferrin-selenium). Subculture of primary cultured epithelial cells was performed at 9-10 days after implantation of collagenase digested glomeruli. Podocytes were identified by the morphology study with scanning electron microscope and inverted microscope, as well as the immunohistochemistry staining (SP methods) study for the expression of keratin, desmin and Wilms' tumor suppressor-1 (WT-1)., Results: Epithelial cells outgrowth from isolated glomeruli appeared after 3 days primary culture and grew to confluence with cobblestone-appearance at 9-10 days. These cobblestone cells were subcultured at this point and gradually conversed into large, flat arborized cells with well-developed processes and microvilli. These arborized cells were negative expression with desmin staining and showed positive expression of cytokeratin and WT-1, which indicated that they were podocytes., Conclusion: Implantating collagenase digested-glomeruli is an easy and feasible method for primary culture of rat glomerular podocytes. WT-1 may serve as a good marker to identify rat glomerular podocytes.

A novel series of polyhalobenzonitrile quinazolin-4(3H)-one derivatives were synthesized and characterized by NMR, IR, MS, and HRMS spectra. All of the newly prepared compounds were screened for antimicrobial activities against four strains of bacteria (Gram-positive bacterial: Staphylococcus aureus and Bacillus cereus; Gram-negative bacterial: Escherichia coli and Pseudomonas aeruginosa) and one strain of fungi (Candida albicans). Among the synthesized compounds, 5-(dimethylamino)-8-(2,4,5-trichloro-isophthalonitrile) quinazolin-4(3H)-one (7k) exhibited significant activity towards Gram-positive bacterial, Gram-negative bacterial, and the fungi strains. The MIC (0.8-3.3μg/mL) and MBC (2.6-7.8μg/mL) for this compound were close to those of nofloxacin, chlorothalonil, and fluconazole, making it the most potent antimicrobial agents in the series., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The protective effects of Da Chai Hu Granules (DCHKL) on islet cells which were incubated with 4 mmol x L(-1) alloxan (AXN) were studied. The viability of islet cells were measured with MTT. Insulin released into medium and in islets was detected by radioimmunoassay. Cell apoptosis rate was determined by flow cytometry. The expression of anti-apoptotic gene Bcl-2 and pro-apoptotic gene Bax in islet cells were measured with RT-PCR (reverse transcription polymerase chain reaction). Serum containing DCHKL can promote the activity of islet cells significantly (P < 0.01). Basal insulin secretion and high glucose-stimulated insulin secretion increased significantly (P < 0.01). Serum containing DCHKL can inhibit apoptosis of islet cells, the ratio of apoptosis was decreased. Serum containing DCHKL increased expression of Bcl-2 mRNA and decreased expression of Bax mRNA. DCHKL can significantly promote proliferation of islet cells and increase the amount of basal secretion of pancreatic islet cells and high glucose-stimulated insulin secretion. The expression of Bcl-2 increased significantly. The expression of Bax decreased significantly. DCHKL have a protective effect on the islet cells.

The goal of mechanically ventilating patients with acute respiratory distress syndrome (ARDS) is to ensure adequate oxygenation and minimal ventilator-associated lung injury. Non-invasive ventilation should be cautiously used in patients with ARDS. Protective ARDS mechanical ventilation strategies with low tidal volumes can reduce mortality. Driving pressure is the most reasonable parameter to optimize tidal volume. Available evidence does not support the routine use of higher positive end expiratory pressure (PEEP) in patients with ARDS. The optimal level of PEEP may be titrated by the inflection point obtained from static pressure-volume curve. Promising therapies include prone position ventilation, high frequency oscillatory ventilation and extracorporeal membrane oxygenation as salvage treatment. While mechanically ventilating, it is also important for ARDS patients to maintain spontaneous breathing via assisted ventilation mode such as bilevel positive airway pressure, pressure support ventilation and neurally adjusted ventilation assist. Exogenous surfactant, inhaled nitric oxide, bronchodilators, airway pressure release ventilation and partial liquid ventilation are not recommended therapies.

Aims: The damage of human brain vascular endothelial cells (HBVECs) is the key pathogenesis of diabetes-associated cerebral vascular complications. The aim of this study was to elucidate the effects of glutathione (GSH) on free fatty acids (FFAs)-induced HBVECs apoptosis, oxidative stress, and the involved possible signaling pathway., Methods: After culturing HBVECs for 72 h with GSH and FFAs, we determined cell proliferation by CCK8, detected apoptosis by caspase-3 and Annexin V-FITC/PI staining, and judged oxygen stress by determining the reactive oxygen species (ROS) and the mitochondrial membrane potential (MMP). We investigated whether the Akt pathway was involved in FFAs-induced signaling pathway alteration and whether GSH influenced the above effects., Results: After being cultured in 200 μM FFAs for 72 h, the HBVECs proliferation significantly decreased; HBVECs apoptosis increased; the ROS levels increased; and the HBVECs MMP subsequently decreased. FFAs induced a significant decrease in phosphorylated active Akt. These alterations were obviously prevented when 1 mM GSH was added to culture medium containing FFAs, and the above effects of GSH were blocked by Akt inhibitor., Conclusion: GSH may prevent FFAs-induced HBVECs damage, oxidative stress, and apoptosis through activating the Akt pathway., (© 2013 Blackwell Publishing Ltd.)

Objective: Preclinical studies have demonstrated that exogenous mesenchymal stem cells (MSCs) may ameliorate kidney damage and enhance repair of renal ischemia reperfusion injury (IRI). This review will focus on the mechanism for accelerating repair of renal IRI by MSCs. Several chemokine receptors such as CXCR4 and CD44 are related to MSCs trafficking to post-ischemic kidney. MSCs differentiate into tubular epithelial cells, which is not the predominant mechanism for repair of the damaged kidney. Instead, MSCs exert their therapeutic effect mainly through paracrine action via a variety of cytokines and microvesicles, and the paracrine actions of infused MSCs work to activate intrinsic kidney cells, promote angiogenesis, inhibit oxidative stress and reduce apoptosis, inflammation and renal fibrosis.

Background: Asthma is a complex disease involving genetic and environment interactions. Atopy is a strong risk factor for asthma. The airway epithelium not only forms a physical barrier but also provides immune defense against harmful materials. To explore the effects of airway epithelium on asthma, we hypothesized that environmental injuries could act on bronchial epithelial cells and damage the physical barrier, which might facilitate allergens to stimulate immunoreactions and play an important role in the pathogenesis of asthma., Methods: Thirty eight-week-old male Wistar rats were randomly divided into five groups with six rats in each group: control group, asthma group, ovalbumin (OVA) + OVA group, lipopolysaccharide (LPS) group and LPS + OVA group. In the control group, 0.9% saline was injected intraperitoneally on day 1. Fourteen days later, the rats were exposed to aerosolized 0.9% saline. In the asthma group, the rats were sensitized with an injection of 10 mg of OVA, followed by an aerosolized 2% OVA challenge 14 days later. The OVA + OVA group was sensitized by an inhalation 2% OVA, 20 minutes a day, from day 1 to day 7, and then OVA challenged in the same way as the asthma group. In the LPS group, LPS (200 µl, 1 µg/µl) was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with saline as in the control group. While in the LPS + OVA group, LPS (200 µl, 1 µg/µl) was given by airway on day 1 and day 3, with a simultaneous aerosol inhalation of 2% OVA for 20 minutes a day from day 1 to day 7. Fourteen days later, the rats were challenged with OVA as in the asthma group. The expression of interleukin (IL)-4, interferon-gamma (IFN-γ) and thymic stromal lymphopoietin (TSLP) in the lungs was detected by reverse transcription polymerase chain reaction (RT-PCR) and the pulmonary pathological changes were also observed. The level of IL-4, IFN-γ and IgE in plasma was detected by enzyme-linked immunosorbent assay (ELISA). Bronchoalveolar lavage fluid (BALF) was collected to conduct differential cell counts. Flow cytometry analysis was also used to count Th1 and Th2 cells., Results: The pathological changes in the LPS + OVA group were similar to the asthma group, while in other groups, the pathological changes were not obvious. The ratio of lymphocytes in BALF, IL-4/IFN-γ in plasma and the expression of the TSLP and IL-4 in the asthma and LPS + OVA groups were higher than in the control group and the OVA + OVA group (P < 0.05). The level of IgE was higher in the asthma, LPS and LPS + OVA groups than in the control group and the OVA + OVA group (P < 0.05). By flow cytometry analysis, the Th1/Th2 ratio was lower in the LPS + OVA and asthma groups than in other groups (P < 0.05)., Conclusions: The experiment results show that the injury to the bronchial epithelial layer may be the initial event of allergic responses. This finding implies that a rational approach to therapeutics would be to increase the resistance of the airways to environmental injuries rather than concentrating on suppressing inflammation.

Background: Growing preclinical evidence shows that zoledronic acid (ZOL) exhibits direct antitumor activity in various cancer cell lines. However, the cytotoxic effects of ZOL on human hepatocellular carcinoma (HCC) cells have not been established. In the present study, we investigated the effect of ZOL on HCC both in vitro and in vivo., Methods: Cytotoxicity and cell cycles were assessed with Sulforhodamine B colorimetric assay and flow cytometry. Expression levels of cell cycle phase-linked proteins were examined. The effect of ZOL on HCC in vivo was explored based on H22-subcutaneous injection (s.c.) and H22-intraperitoneal injection (i.p.) mice model., Results: ZOL inhibited the growth of SK-HEP-1 and H22 cells and induced S-phase arrest through downregulating cdc2 protein and upregulating cyclin A. It inhibited the growth of s.c tumors, and increased the survival of both H22-s.c. and H22-i.p. mice in vivo., Conclusion: ZOL inhibits growth of HCC cells in vitro and in vivo.

Objective: To investigate the spray of niclosamide ethanolamine salt on prevention of bovine schistosomiasis in the field so as to provide a technical support for the improvement of schistosomiasis control strategy., Methods: A total of 160 buffalo were selected as experimental objects marked by ear-mark numbers. All the buffalo were administered with praziquantel and then randomly divided into 3 groups, which were sprayed with niclosamide ethanolamine salt (500 ml per head) every 15 d (Group A), every 30 d (Group B) and an agent without niclosamide ethanolamine salt every 15 d (Group C as the control), respectively. The buffalo's droppings were collected to examine the eggs of schistosome every 30 days during the trial., Results: Ninety days after the spraying, the prevalence rates of schistosomiasis were 4.00%, 4.08%, and 24.49% in the Group A, Group B, and Group C, respectively. Compared with the control group (Group C), the decline prevalence rates of schistosomiasis were 83.67% and 83.34% in the Group A and Group B, respectively., Conclusions: The buffalo spraying with 1% niclosamide ethanolamine salt can reduce schistosomiasis prevalence in bovine, that is this intervention has an obvious protective effect.

Human flesh search (HFS), a phenomenon that has recently emerged over the Internet, represents the interaction between the virtual and real worlds. The term "HFS" is equivalent to "cyber manhunt" in the West, although there were more large-scale HFS events reported in the East recently. While the majority of academic articles on HFS have focused on the Chinese context, the phenomenon has also been reported in many countries and involves diverse issues such as the controversy between privacy violation and public opinion. Based on 16 HFS references, a review paper by Chen and Sharma summarizes core issues on growth, incidents, distinctive attributes, key benefits and drawbacks, findings, and research gaps and opportunities. Echoing their call for a global HFS context, the current article provides a Taiwanese HFS context based on 32 reported incidents in Taiwan. To conduct an incremental HFS review, this study expands the reference base to 33 carefully selected academic articles from China and Taiwan. The review findings range from 6 derived HFS perspectives supplementing each article, 12 frequently mentioned HFS concepts, and 4 additional research directions. The resulting comprehensive knowledge of HFS, along with that contributed by Chen and Sharma, can be considered a useful reference framework for future HFS studies and policy making.

Objective: To detect and analyze the serum protein biomarkers in mice with acute Toxoplasma gondii infection., Methods: The serum samples from 8 C57BL/6J mice with acute Toxoplasma gondii infection and 8 normal healthy paired mice were prepared with WCX magnetic beads, and then analyzed on PBS II -C mass spectrometer reader. The protein spectra of the serum samples were normalized by the Ciphergen Protein Chip software. The peak labeling was performed by the Biomarker Wizard software. The specific protein biomarkers were screened by the Biomarker Pattern software to construct a diagnostic model for acute Toxoplasma gondii infection., Results: A total of 13 distinguished proteomic peaks were detected. Nine peaks were of up-regulated expressions including m/z values of 1 932.76, 1 976.85, 2 090.53, 5 004.5, 5 776.01, 5 803.05, 5 847.99, 5 877.51 and 7 501.58, respectively; and four peaks were of down-regulated expressions including m/z values of 1 866.40,4 063.71, 8 120.31 and 8 203.83, respectively., Conclusion: The potential protein biomarkers for acute Toxoplasma gondii infection are discovered in mouse serum by MALDI-TOF-MS combined with WCX magnetic beads.

Dihydroartemisinin, formerly known as an antimalarial drug, is the main metabolite of the mother compound artemisinins, as well as of artemether and artesunate. It has been shown that the drug exhibits antischistosomal efficacy against Schistosoma japonicum. The purpose of the current study was to assess the in vivo effect of dihydroartemisinin against Schistosoma mansoni infection in mice. Drugs at a single oral dose of 300 mg/kg were given to mice to assess the efficacy against different developmental stages of the parasite; juvenile and adult S. mansoni were treated with single doses of dihydroarteminisin with different regimens (at 200, 300, 400 or 600 mg/kg) in the stage of drug sensitivity, and the dose-response relationship was assessed; and the effect of multiple doses (at 200, 300 or 400 mg/kg) on juvenile and adult S. mansoni was also observed. The results showed that a single oral dose (300 mg/kg) of dihydroartemisinin reduced total worm burdens by 13.8-82.1% and female worm burdens by 13-82.8%, and the greatest reductions were seen when treatment was given on day 21 post-infection, with total and female worm burden reductions of 82.1% and 82.8%. Administration of a single oral dose of dihydroartemisinin on day 21 post-infection with different drug dosage (at 200, 300, 400 or 600 mg/kg) reduced total worm burdens by 70.3-87.3% and female worm burdens by 73.5-92.4%, depending on dosage. Similar treatments given on day 49 post-infection reduced total worm burdens by 48.7-68.73% and female worm burdens by 63.25-94.6%. There was obvious dose-response relationship of dihydroartemisinin against the schistosomula and adult worms of S. mansoni observed. Administration with dihydroartemisinin at oral doses of 200, 300 and 400 mg/kg, given once on each of days 20-22 post-infection of three successive days, reduced total worm burdens by 88.5-90.1% and female worm burdens by 89.2-92.1%, depending on dosage. Similar treatments given once on each of days 48-50 post-infection reduced total worm burdens by 60-70.3% and female worm burdens by 77.5-94.9%. It is concluded that dihydroartemisinin exhibits in vivo activity against various developmental stages of S. mansoni, particularly the 21-day schistosomula, and there is obvious dose-response relationship of dihydroartemisinin against the schistosomula and adult worms of S. mansoni observed.

Objective: To investigate the changes of sensitivity to praziquantel (PZQ) about PZQ-resistant isolates of Schistosoma japonicum established in laboratory by means of the resistance-inducement method during the stages of adult worms, cercariae and miracidia, so as to provide the basis for establishing the sensitivity-detecting technique to praziquantel., Methods: A Jiangsu laboratory-maintaining isolate and a Hunan field-collecting isolate of S. japonicum that were never treated with PZQ were as PZQ-susceptible isolates, and two PZQ-induced isolates that were established via drug-treated passage in laboratory were as PZQ-resistant isolates. Mice were infected with S. japonicum cercariae collected from above four isolates each. Thirty-five days after the infection, the mice were divided into 6 groups and administered orally with PZQ at dosages of 0, 37.5, 75, 150, 300 mg/kg and 600 mg/kg, respectively. All the mice were sacrificed two weeks after the treatment, and all the adult worms in the hepatic and portomesenteric veins were recovered and counted. The mean worm burden and reductions were calculated and input into Graphpad Prism 5.0 software, and the PZQ ED50 values of four isolates were calculated by the software. The cercariae of above four isolates were exposed to 10(-5), 5 x 10(-6), 10(-6), 5 x 10(-7), 10(-7) mol/L PZQ solutions for 20, 40, 60, 80, 100 min and the changes of tail shedding were observed under a dissecting microscope, then the tail shedding rates of cercariae were calculated. The miracidia of above four isolates were exposed to 5 x 10(-6), 10(-6), 5 x 10(-7), 10(-7) mol/L PZQ solutions for 1, 3 and 5 min and the morphological changes were observed under a dissecting microscope, then the morphological change rates of miracidia were calculated., Results: The PZQ ED50 values of PZQ-susceptible and PZQ-resistant isolates of Jiangsu were 147.7 mg/kg and 565.5 mg/kg, respectively, and the PZQ ED50 values of PZQ-susceptible and PZQ-resistant isolates of Hunan were 151.8 mg/kg and 467.2 mg/kg, respectively. When the cercariae were exposed to 10(-5) mol/L PZQ solution over 20 min, the tail shedding rate of cercariae from PZQ-susceptible isolate of Jiangsu was 68.8%, and the tail shedding rate of cercariae from PZQ-resistant isolate of Jiangsu was 38.2% (P < 0.01). When the cercariae were exposed to 10(-7) mol/L PZQ solution over 100 min, the tail shedding rate of cercariae from PZQ-susceptible isolate of Jiangsu was 15.9%, and the tail shedding rate of cercariae from PZQ-resistant isolate of Jiangsu was 6.7% (P < 0.01). When the cercariae were exposed to 10(-5) mol/L PZQ solution over 20 min, the tail shedding rates of cercariae from PZQ-susceptible isolate of Hunan was 59.4%, and the tail shedding rates of cercariae from PZQ-resistant isolate of Hunan was 54.6% (P < 0.05). When the cercariae were exposed to 5 x 10(-7) mol/L PZQ solution over 40 min, the tail shedding rates of cercariae from PZQ-susceptible isolate of Jiangsu was 34.3%, and the tail shedding rates of cercariae from PZQ-resistant isolate of Jiangsu was 18.4% (P < 0.01). When the miracidia were exposed to 5 x 10(-7) mol/L and 10(-7) mol/L PZQ solutions for 1, 3 and 5 min respectively, the morphological change rates of miracidia from PZQ-susceptible isolates of Jiangsu and Hunan were significantly higher than those of PZQ-resistant isolates (P < 0.01)., Conclusions: PZQ-resistant isolates of S. japonicum has been established in mice with sub-curative doses of PZQ by artificial selection in laboratory, and their sensitivities to PZQ are significantly lower than those of the isolates never treated with PZQ. The drug-resistance could exhibit in the stages of adult worms, cercariae and miracidia. The PZQ ED50 value of adult worms, the tail shedding rates of cercariae and the morphological change rates of miracidia as quantitative indicators can be used for monitoring the S. japonicum sensitivity to PZQ.

Objective: To investigate the possibility of the emergence of praziquantel resistance in Schistosoma japonicum in Mainland China under drug pressure., Methods: S. japonicum cercaria were released from the infected Oncomelania hupensis snails collected from the marshland in Hunan Province that was endemic for schistosomiasis japonica and raised in the laboratory of Jiangsu Institute of Parasitic Diseases, and mice were infected. O. hupensis snails were infected with miracidia hatched from the schistosome mature eggs that were isolated from the liver of the infected mice. The life cycles of a field isolate and a laboratory passage isolate of S. japonicum were established in laboratory via the cycle of mouse-snail. The mice were infected with 40 cercariae each, 35 days later post-infection, were grouped randomly into control and resistance-induced groups. All the mice in the control group were sacrificed on day 45 post-infection, and any adult S. japonicum worms in the hepatic and portomesenteric veins were recovered and counted, and the worm burdens were calculated. The mice in the resistance-induced group were administered orally with the sub-curative dose of praziquantel, and were sacrificed 22 days post-treatment. Any adult S. japonicum worms in the hepatic and portomesenteric veins were recovered and counted, and the worm burdens and reduction in the worms recovered which were obviously caused by the praziquantel treatment were calculated. The eggs in the liver of the mice in the resistance-induced group were isolated and hatched to yield miracidia, and then the snails were again infected with the newly hatched miracidia to complete the first-passage inducement. After raising in laboratory at 25 degrees C for 60-70 days post-infection, the infected snails were isolated and shed cercaria, and the mice were infected with the newly released cercaria to start a new passage of resistance-inducement. The oral dose of praziquantel for the first-passage inducement was 100 mg/kg, and an additional 100 mg/kg was given every 2-3 passages. The mice were infected with cercariae of the parasite with 8-passge resistance-inducement and the isolate that was not induced, and 35 days post-infection, were administered with praziquantel at a single oral doses of 300 mg/kg and 600 mg/kg respectively. All the mice were sacrificed 14 days post - treatment, and any adult S. japonicum worms in the hepatic and portomesenteric veins were recovered and counted, and the reductions in the worm burdens were calculated to assess the sensitivity of praziquantel in the parasites after 8-passage resistance-inducement., Results: Two isolates of Jiangsu laboratory passage of Jiangsu and field isolate of Hunan were established in the laboratory, and a total 8-passage resistance -inducement was completed. For the laboratory passage isolate, the worm burden reduction was 22.3% post-treatment with 100 mg/kg praziquantel during the first-passage inducement, and 53.7% post-treatment with 300 mg/kg praziquantel during the 8-passage inducement, appearing that the worm burden reduction increased with the increasing dose of praziquantel. For the field-collected isolate, the worm burden reduction was 66.8% post-treatment with 100 mg/kg praziquantel during the first-passage inducement, and 20.6% post-treatment with 300 mg/kg praziquantel during the 8-passage inducement, indicating that the worm burden reduction markedly decreased with the increasing dose of praziquantel. The worm burden reductions were 71.5% and 97.4% respectively for the mice infected with the non-induced laboratory passage isolate, while administered with praziquantel at doses of 300 mg/kg and 600 mg/kg respectively. After 8-passage treatment with sub-curative praziquantel, the corresponding worm burden reductions decreased to 32.6% and 68.1%, respectively. For the field-collected isolate without inducement, the worm burden reductions in the mice were 70.8% and 97.5% respectively post-treatment with praziquantel at doses of 300 mg/kg and 600 mg/ kg respectively, and the corresponding worm burden reductions decreased to 45.7% and 61.9%, respectively after 8-passage treatment. COCLUSIONS: S. japonicum (strain of Mainland China) is able to develop resistance to praziquantel under continuous drug pressure. However, there are variations in the potential of the emergence of resistance due to various susceptibility of praziquantel among different isolates. The successful establishment of praziquantel-resistant strain of S. japonicum (Mainland China) will provide the basis for exploring the mechanism of praziquantel resistance in S. japonicum, and developing related techniques to detect and monitor praziquantel resistance.

Artemether and artesunate, derivatives of the antimalarial artemisinin, as well as their main metabolite, dihydroartemisinin, all exhibit antischistosomal activities. The purpose of the current study was to compare the effects of artemether, artesunate and dihydroartemisinin administered orally at multiple doses or combination in treatment of mice infected with Schistosoma japonicum. We carried out experiments with mice, infected with 40 cercariae of S. japonicum, and treated with artemether, artesunate and dihydroartemisinin (all at a single dose of 300 mg/kg, and the dose of the mixed three drugs is also 300 mg/kg) at multiple doses or combination therapy on days 6-8 or 34-36 post-infection. Administration with artemether, artesunate or dihydroartemisinin for 3 successive days reduced total worm burdens by 79.5-86% (30.86 ± 4.98 of mean total worm burden in control), female worm burdens by 79.4-86.7% (11.29 ± 2.63 of mean female worm burden in control) (all P values <0.01 vs. control), depending on different treatment protocols given on days 6-8 post-infection. However, no differences were seen between each treatment group (all P > 0.05). While the same treatment was given on days 34-36 post-infection, total worm burden reductions of 73.8-75.8% were achieved (29.44 ± 3.36 of mean total worm burden in control), which were significant when compared with the untreated control group (all P values <0.01). In all different treatment groups, female worm reductions (ranging from 88.7% to 93.1%, while the mean female worm burden in control is 10.33 ± 1.80) were consistently higher than the total worm reductions, resulting always in significantly lower female worm burdens when compared to the corresponding control (all P values < 0.01). However, there were no significant differences found between each treatment group (all P values >0.05). It is concluded that artemether, artesunate and dihydroartemisinin can be used to control schistosomiasis japonica, as a strategy to prevent S. japonicum infection. Administration with artemether, artesunate and dihydroartemisinin at multiple doses or in combined treatment damages both juvenile and adult S. japonicum, without statistically significant differences among the three drugs at the same dose.