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Background: Maintenance hemodialysis (MHD) patients with HIV infection have a high mortality rate. A number of factors influence the survival rate of these patients. Objectives: Our aim was to determine the risk factors of survival time of MHD patients with HIV. Methods: 30 MHD patients with HIV were retrospectively investigated. The cases were divided into two groups predicated on the dialysis time (≤1year, ＞1year). Risk factors affecting the survival of patients were compared. Cox regression and the life table method were used to predict the independent risk factors affecting long-term survival. Results: Among 30 MHD patients with HIV infection, the 1-year survival rate was 86.7% (26/30) and the 5-year survival rate was 60% (18/30). Cox regres-sion showed that HIV clinical phase and urea clearance index (KT/V) were in-dependent risk factors for the long-term survival of MHD patients with HIV. Conclusion: Effective antiviral therapy (ART), control of complications of chronic kidney disease and qualified dialysis adequacy may become important survival factors affecting MHD patients with HIV infection.

Objective: We aimed to evaluate the effectiveness of topical tranexamic acid (TXA) versus topical vasoconstrictors in the management of epistaxis via a systematic review and meta-analysis. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were followed for the meta-analysis. We systematically searched Embase, Web of Science, Cochrane Library, CNKI, and PubMed for randomized controlled trials (from inception to August 2022; no language restrictions), comparing the effect of topical TXA and topical vasoconstrictors on the treatment of epistaxis. The Q test was used to evaluate heterogeneity, and funnel plots were utilized to identify bias. For the meta-analysis, the fixed-effects model was employed, and the t-test was utilized to determine significance. Results: Of 1012 identified studies, 5 were found to be eligible for our analysis. In total, 598 patients were included; 297 of them received TXA and 301 received vasoconstrictors. Hemostasis was more likely to be achieved at the first re-assessment in patients treated with TXA. Subgroup analysis indicated patients treated with TXA to have less likelihood of bleeding recurrence, compared to patients treated with vasoconstrictors. The detected time interval of rebleeding was 10 min, between 24h to 72h, and after 7 days, respectively, and the differences were significant between the two groups of patients treated with TXA and vasoconstrictors. Conclusion: Topical TXA was associated with better post-treatment hemorrhagic arrest rates compared to topical vasoconstrictors in the management of epistaxis.

Meiling Jin,1,2,* Wenwen Ren,3,* Weiguang Zhang,2 Linchang Liu,2,4 Zhiwei Yin,2,5 Diangeng Li6 1Department of Nephrology, Beijing-Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Nephrology, Chinese People’s Liberation Army General Hospital, Chinese People’s Liberation Army Institute of Nephrology, State Key Laboratory of Kidney Diseases (2011DAV00088), National Clinical Research Center for Kidney Diseases, Beijing, 100853, People’s Republic of China; 3Department of Nephrology, Beijing Ditan Hospital,Capital Medical University, Beijing, 100015, People’s Republic of China; 4Department of Nephrology, Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, 100039, People’s Republic of China; 5College of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 6Department of Academic Research, Beijing-Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Diangeng LiDepartment of Academic Research, Beijing-Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaTel/Fax +86 10-85231049Email lidiangeng@126.comZhiwei YinCollege of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; Department of Nephrology, Chinese People’s Liberation Army General Hospital, Chinese People’s Liberation Army Institute of Nephrology, State Key Laboratory of Kidney Diseases (2011DAV00088), National Clinical Research Center for Kidney Diseases, Beijing, 100853, People’s Republic of ChinaTel/Fax +86 10-66937010Email zhiwei_yin@126.comPurpose: This study aimed to explore the underlying mechanisms of Shenyankangfu tablet (SYKFT) in the treatment of glomerulonephritis (GN) based on network pharmacology, machine learning, molecular docking, and experimental validation.Methods: The active ingredients and potential targets of SYKFT were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, the targets of GN were obtained through GeneCards, etc. Perl and Cytoscape were used to construct an herb-active ingredient–target network. Then, the clusterProfiler package of R was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. We also used the STRING platform and Cytoscape to construct a protein–protein interaction (PPI) network, as well as the SwissTargetPrediction server to predict the target protein of the core active ingredient based on machine-learning model. Molecular-docking analysis was further performed using AutoDock Vina and Pymol. Finally, we verified the effect of SYKFT on GN in vivo.Results: A total of 154 active ingredients and 255 targets in SYKFT were screened, and 135 targets were identified to be related to GN. GO enrichment analysis indicated that biological processes were primarily associated with oxidative stress and cell proliferation. KEGG pathway analysis showed that these targets were involved mostly in infection-related and GN-related pathways. PPI network analysis identified 13 core targets of SYKFT. Results of machine-learning model suggested that STAT3 and AKT1 may be the key target. Results of molecular docking suggested that the main active components of SYKFT can be combined with various target proteins. In vivo experiments confirmed that SYKFT may alleviate renal pathological injury by regulating core genes, thereby reducing urinary protein.Conclusion: This study demonstrated for the first time the multicomponent, multitarget, and multipathway characteristics of SYKFT for GN treatment.Keywords: shenyankangfu tablet, glomerulonephritis, network pharmacology, machine learning, molecular docking

Oysters have high nutritional value but are rare in processing products. In this study, we developed an innovative product of oyster combined with soybean paste. The processing conditions and flavoring formulations of canned oysters were optimized using orthogonal experiments. Headspace solid-phase microextraction (HP-SPME) combined with gas chromatography-mass spectrometry (GC-MS) was applied to evaluate the volatile compounds related to the aroma. The results showed that the optimal canned oyster was oyster dried at 90 °C for 20 min and oil-fried at 150 °C for 6 min with the adding flavoring formula of 20% soybean paste, 0.5% vinegar, and 0.01% I+G (disodium 5'-presenting nucleotide) based on the weight of oyster. Canned soybean paste oysters enrich volatile components related to aroma including 2-octanol, 2-furanmethanol, benzaldehyde, and 2-pentylfuran. The canned soybean paste oyster is a high-valued nutrient including protein, fat, zinc, and taurine. This study will provide processing conditions for favorite instant processed oysters with soybean paste supplementary and deep insight into the flavor formation.

The development of the sustainable economy has gradually become a consensus, and corporate social responsibility (CSR) is the key to achieving the sustainable development. However due to the implementation of CSR will increase the cost burden of enterprises, some companies are even unwilling to fulfill CSR. At this time, the government often encourages companies to fulfill CSR through subsidies, and consumers are willing to pay a higher price for CSR products. Therefore, this article focuses on the supply chain decision-making analysis problem in the sustainable supply chain. Based on consumer preference for CSR products, considering CSR and government subsidies, some relevant models are constructed to analyze decisions under different power structures and different subsidy situations, then the article compares them and finally draws relevant conclusions. The study found that the higher the consumer's preference, the higher the product sales and CSR level. In addition, government subsidies to manufacturers or consumers have the same effect. Among the three power structures, the overall benefit of supply chain is the highest in VN (Vertical Nash) power structure, so the government should play a leading role and try to narrow any possible gap of channel power.

The adult olfactory epithelium (OE) regenerates sensory neurons and nonsensory supporting cells from resident stem cells after injury. How supporting cells contribute to OE regeneration remains largely unknown. In this study, we elucidated a novel role of Ym2 (also known as Chil4 or Chi3l4), a chitinase-like protein expressed in supporting cells, in regulating regeneration of the injured OE in vivo in both male and female mice and cell proliferation/differentiation in OE colonies in vitro. We found that Ym2 expression was enhanced in supporting cells after OE injury. Genetic knockdown of Ym2 in supporting cells attenuated recovery of the injured OE, while Ym2 overexpression by lentiviral infection accelerated OE regeneration. Similarly, Ym2 bidirectionally regulated cell proliferation and differentiation in OE colonies. Furthermore, anti-inflammatory treatment reduced Ym2 expression and delayed OE regeneration in vivo and cell proliferation/differentiation in vitro, which were counteracted by Ym2 overexpression. Collectively, this study revealed a novel role of Ym2 in OE regeneration and cell proliferation/differentiation of OE colonies via interaction with inflammatory responses, providing new clues to the function of supporting cells in these processes. SIGNIFICANCE STATEMENT The mammalian olfactory epithelium (OE) is a unique neural tissue that regenerates sensory neurons and nonsensory supporting cells throughout life and postinjury. How supporting cells contribute to this process is not entirely understood. Here we report that OE injury causes upregulation of a chitinase-like protein, Ym2, in supporting cells, which facilitates OE regeneration. Moreover, anti-inflammatory treatment reduces Ym2 expression and delays OE regeneration, which are counteracted by Ym2 overexpression. This study reveals an important role of supporting cells in OE regeneration and provides a critical link between Ym2 and inflammation in this process.

Tibet Gaoshan Yak (Bos grunniens) is a local Yak breed that mainly produces meat in Tibet Autonomous Region, China. In this study, the complete mitochondrial genome of Tibet Gaoshan Yak was sequenced. The total length of the mitochondrial genome is 16,323 bp, and the base composition is 33.71% for A, 13.21% for G, 27.27% for T, and 25.81% for C. The genome includes 13 protein-coding genes (ND1-ND6, ND4L, COX1-COX3, ATP6, ATP8, and CYTB), two rRNA genes (12S rRNA and 16SrRNA), 22 tRNA genes, and a noncoding control region (D-loop). Phylogenetic analysis showed that Tibet Gaoshan Yak has the closest relationship with Polled Yak. The sequence analysis provided in this study will be helpful to the management of Yak breeds, the origin, and evolution of Yak, and the protection and utilization of genetic resources.

Purpose This paper aims to deal with the coordination problem of the supply chain through cost sharing of corporate social responsibility (CSR) and government subsidy. Design/methodology/approach With respect to the coordination problem of the supply chain with CSR, this paper constructs a three-stage game model consisting of a dominant retailer, n suppliers and government. From the perspective of cost sharing and government subsidies, this paper discussed the decentralized and centralized decision-making, respectively. On this basis, this paper designed a coordination mechanism considering both cost sharing and government subsidies and explore the impact of cost sharing rate and government subsidy rate on CSR efforts, members’ profits and social welfare. Findings CSR can improve the profits of supply chain members and the overall performance of the supply chain. Then the profits of supply chain nodal enterprises will be affected by the fulfillment level of CSR of their partners. Furthermore, excessive CSR will erode the supply chain profits and cause resource waste. High CSR costs often make retailers low CSR effort level, while a high CSR cost sharing rate can reduce the profits of suppliers and the supply chain. In addition, excessive government subsidies will lead to the decline of social welfare. Excessive government subsidies will cause the dependence of enterprises and affect their operating efficiency. Practical implications The proposed coordination mechanism can effectively do with the coordination problem of the supply chain. Originality/value The proposed coordination mechanism considering cost sharing and government subsidies simultaneously can effectively deal with conflict problems and guarantee the supply chain members and the supply chain to maximize their profits and social welfare.

Olfactory dysfunctions, including hyposmia and anosmia, affect ~100 million people around the world and the underlying causes are not fully understood. Degeneration of olfactory sensory neurons and incapacity of globose basal cells to generate olfactory sensory neurons are found in elder people and patients with smell disorders. Thus, olfactory stem cell may function as a promising tool to replace inactivated globose basal cells and to generate sensory neurons. Methods: We established clonal expansion of cells from the murine olfactory epithelium as well as colony growth from human olfactory mucosa using Matrigel-based three-dimensional system. These colonies were characterized by immunostaining against olfactory epithelium cellular markers and by calcium imaging of responses to odors. Chemical addition was optimized to promote Lgr5 expression, colony growth and sensory neuron generation, tested by quantitative PCR and immunostaining against progenitor and neuronal markers. The differential transcriptomes in multiple signaling pathways between colonies under different base media and chemical cocktails were determined by RNA-Seq. Results: In defined culture media, we found that VPA and CHIR99021 induced the highest Lgr5 expression level, while LY411575 resulted in the most abundant yield of OMP+ mature sensory neurons in murine colonies. Different base culture media with drug cocktails led to apparent morphological alteration from filled to cystic appearance, accompanied with massive transcriptional changes in multiple signaling pathways. Generation of sensory neurons in human colonies was affected through TGF-β signaling, while Lgr5 expression and cell proliferation was regulated by VPA. Conclusion: Our findings suggest that targeting expansion of olfactory epithelium/mucosa colonies in vitro potentially results in discovery of new source to cell replacement-based therapy against smell loss.

Copy Number Variation (CNV) is the major manner for the variation of genome structure, which is associated with numerous important traits. The heat shock factor 1 (HSF1) gene is a stress response transcriptional regulator. It participates in the heat shock response, simultaneously participated in the development of tissue. The objective of this research was to explore the influence of CNV of the HSF1 gene on the growth traits of the Ashidan yak. In this study, the growth traits (withers height, body weight, chest girth, and body length) of 274 Ashidan yaks were divided into four stages (6, 12, 18, and 30 months old). Moreover, quantitative polymerase chain reaction (qPCR) was exploited for determining the HSF1 gene relative expression level, and SPSS software was utilized for the statistical analysis. The outcomes indicated that HSF1-CNV was significantly associated with body length (p 0.05) and was extremely significant associated with withers height (p 0.01) of 18-month-old Ashidan yaks. Besides, the HSF1 relative expression in heart and muscle was higher than that existed in other tissues (p 0.01). The outcomes suggested that the CNV of HSF1 gene would affect the growth and development of the Ashidan yak, which is conducive to the early breeding of yak.

Olfactory sensory neurons (OSNs) located in the olfactory epithelium (OE) detect thousands of volatile environmental odors to form the sense of smell. OSNs are generated from basal cells, which show the characteristics of progenitor/stem cells. In the mammalian OE, persistent neurogenesis occurs during lifetime, providing a unique model to study the tissue turnover and fate determination of stem cells.

Sense of taste is central to evaluate food before digestion. Taste stem cells undergo constant differentiation throughout the life. However, the mechanism underlying the generation of taste receptor cells is still not clear. Here, we cultured taste organoids from either Lgr5+ or Lgr5-cells, and found the preferential generation of Car4+ and Gustducin + taste receptor cells in organoids derived from Lgr5+ cells in circumvallate, foliate or fungiform papillae. Taste organoids derived from Lgr5+ cells in circumvallate papillae of neonatal mice showed stronger capacity to generate taste receptor cells compared to the organoids from Lgr5+ cells of the adult circumvallate papillae. Massive transcriptional differences were found in multiple signaling pathways including taste transduction between organoids derived from circumvallate papillae of adult and neonatal mice. Inhibiting the Notch signaling pathway by LY411575 enhanced taste receptor cell generation in organoids from circumvallate papillae and modulated multiple signaling pathways. Thus, we concluded that receptor cell generation in taste organoids was age-related and regulated via multiple signaling pathways.

G protein-coupled receptors (GPCRs) conserve common structural folds and activation mechanisms, yet their ligand spectra and functions are highly diversified. This work investigated how the functional variations in olfactory GPCRs (ORs)-the largest GPCR family-are encoded in the primary sequence. With the aid of site-directed mutagenesis and molecular simulations, we built machine learning models to predict OR-ligand pairs as well as basal activity of ORs. In vitro functional assay confirmed 20 new OR-odorant pairs, including 9 orphan ORs. Residues around the odorant-binding pocket dictate the odorant selectivity/specificity of the ORs. Residues that encode the varied basal activities of the ORs were found to mostly surround the conserved motifs as well as the binding pocket. The machine learning approach, which is readily applicable to mammalian OR families, will accelerate OR-odorant mapping and the decoding of combinatorial OR codes for odors.

The Notch signaling pathway regulates stem cell proliferation and differentiation in multiple tissues and organs, and is required for tissue maintenance. However, the role of Notch in regulation of olfactory epithelium (OE) progenitor/stem cells to maintain tissue function is still not clear. A recent study reported that leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is expressed in globose basal cells (GBCs) localized in OE. Through lineage tracing in vivo, we found that Lgr5+ cells act as progenitor/stem cells in OE. The generation of daughter cells from Lgr5+ progenitor/stem cells is delicately regulated by the Notch signaling pathway, which not only controls the proliferation of Lgr5+ cells and their immediate progenies but also affects their subsequent terminal differentiation. In conditionally cultured OE organoids in vitro, inhibition of Notch signaling promotes neuronal differentiation. Besides, OE lesion through methimazole administration in mice induces generation of more Notch1+ cells in the horizontal basal cell (HBC) layer, and organoids derived from lesioned OE possesses more proliferative Notch1+ HBCs. In summary, we concluded that Notch signaling regulates Lgr5+ GBCs by controlling cellular proliferation and differentiation as well as maintaining epithelial cell homeostasis in normal OE. Meanwhile, Notch1 also marks HBCs in lesioned OE and Notch1+ HBCs are transiently present in OE after injury. This implies that Notch1+ cells in OE may have dual roles, functioning as GBCs in early development of OE and HBCs in restoring the lesioned OE.

The hallmark features of type 2 mucosal immunity include intestinal tuft and goblet cell expansion initiated by tuft cell activation. How infectious agents that induce type 2 mucosal immunity are detected by tuft cells is unknown. Published microarray analysis suggested that succinate receptor 1 (Sucnr1) is specifically expressed in tuft cells. Thus, we hypothesized that the succinate–Sucnr1 axis may be utilized by tuft cells to detect certain infectious agents. Here we confirmed that Sucnr1 is specifically expressed in intestinal tuft cells but not in other types of intestinal epithelial cells, and demonstrated that dietary succinate induces tuft and goblet cell hyperplasia via Sucnr1 and the tuft cell-expressed chemosensory signaling elements gustducin and Trpm5. Conventional mice with a genetic Sucnr1 deficiency (Sucnr1−/−) showed diminished immune responses to treatment with polyethylene glycol and streptomycin, which are known to enhance microbiota-derived succinate, but responded normally to inoculation with the parasitic worm Nippostrongylus brasiliensis that also produces succinate. Thus, Sucnr1 is required for microbiota-induced but not for a generalized worm-induced type 2 immunity.

The fish olfactory receptor ORA family is orthologous to the mammalian vomeronasal receptors type 1. It consists of six highly conserved chemosensory receptors expected to be essential for survival and communication. We deorphanized the zebrafish ORA family in a heterologous cell system. The six receptors responded specifically to lithocholic acid (LCA) and closely related C(24) 5β-bile acids/salts. LCA attracted zebrafish as strongly as food in behavioral tests, whereas the less potent cholanic acid elicited weaker attraction, consistent with the in vitro results. The ORA-ligand recognition patterns were probed with site-directed mutagenesis guided by in silico modeling. We revealed the receptors' structure–function relationship underlying their specificity and selectivity for these compounds. Bile acids/salts are putative fish semiochemicals or pheromones sensed by the olfactory system with high specificity. This work identified their receptors and provided the basis for probing the roles of ORAs and bile acids/salts in fish chemosensation.

Copy number variation (CNV) is a structural variation at the submicroscopic level of the genome, which can affect gene-related phenotypes by changing genes dosage and transcript structure. Hematopoietic prostaglandin D synthase (HPGDS) is a member whose functions are closely related to weight gain and inflammatory diseases of the glutathione S-transferase (GSTs) family. In this study, the growth characteristics (body weight, withers height, body length, and chest girth) of 336 Ashidan yaks were monitored at four stages (6 months, 12 months, 18 months, and 30 months). In addition, CNV of the HPGDS gene was detected, discovered relationships of CNV with growth traits, and explored the level of gene expression. Based on the statistical analysis by IBM SPSS software, significant correlations were observed between HPGDS-CNV and body weight in 12-month-old yak (P 0.01), 18-month-old yak (P 0.001) and 30-month-old yak (P 0.001) and body length in 18-month-old yak (P 0.05) and 30-month-old yak (P 0.05), respectively. Additionally, the individuals with gain copy number type performed better in body weight and body length than those with normal or loss copy number type. To our best of knowledge, this is the first time to make efforts to probe into the role of HPGDS-CNV and its interaction with livestock growth traits. Our results suggested that the CNV of the HPGDS gene may be an active candidate gene for the marker-assisted selection (MAS) of yaks.

To promote social responsibilities of transnational corporation within the present world where such necessary corporation is seriously missing, this paper explores issues of decision-making and coordination of such a two-echelon supply chain that consists of a contract supplier and a dominant manufacturer. Considering the main reasons behind the lack of social responsibilities of multinational corporations, this work develops a model with punishment. Based on this model, we obtain the optimal decision for the supply-chain members under either decentralized decision-making or centralized decision-making. And we analyze whether the penalty rate will have an impact on the input of corporate social responsibility and how it will affect the self-interests of supply chain members. Ultimately, by exploring the decision variables of companies that practice stronger corporate social responsibility, we compare and analyze our models to draw several interesting and practically useful conclusions.

Pricing problems are the core content of product management and supply chain management, so that how to make rational price for different products under a dual-channel supply chain has been an urgent problem to be solved. With respect to the pricing problem of two differentiated products in a dual-channel supply chain consisting of a dominant manufacturer and a retailer, considering different consumer network acceptance for different products, we establish basic demand and profit functions by maximizing consumer utility. Then we exploit game theory to analyze the optimal decisions under single-channel and dual-channel of supply chains, respectively, and explore the impact of different consumer network acceptances on the optimal pricing, demand and profit of supply chains

The Notch signaling pathway regulates stem cell proliferation and differentiation in multiple tissues and organs, and is required for tissue maintenance. However, the role of Notch in regulation of olfactory epithelium (OE) progenitor/stem cells to maintain tissue function is still not clear. A recent study reported that leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is expressed in globose basal cells (GBCs) localized in OE. Through lineage tracing in vivo, we found that Lgr5

Taste cells undergo constant turnover throughout life; however, the molecular mechanisms governing taste cell generation are not well understood. Using RNA-Seq, we systematically surveyed the transcriptome landscape of taste organoids at different stages of growth. Our data show the staged expression of a variety of genes and identify multiple signaling pathways underlying taste cell differentiation and taste stem/progenitor cell proliferation. For example, transcripts of taste receptors appear only or predominantly in late-stage organoids. Prior to that, transcription factors and other signaling elements are upregulated. RNA-Seq identified a number of well-characterized signaling pathways in taste organoid cultures, such as those involving Wnt, bone morphogenetic proteins (BMPs), Notch, and Hedgehog (Hh). By pharmacological manipulation, we demonstrate that Wnt, BMPs, Notch, and Hh signaling pathways are necessary for taste cell proliferation, differentiation and cell fate determination. The temporal expression profiles displayed by taste organoids may also lead to the identification of currently unknown transducer elements underlying sour, salt, and other taste qualities, given the staged expression of taste receptor genes and taste transduction elements in cultured organoids.

Taste cells in taste buds are epithelial sensory cells. Old taste bud cells die and are replaced by new ones generated from taste stem cells. Identifying and characterizing adult taste stem cells is therefore important to understand how peripheral taste tissues are maintained. SOX2 is expressed in oral epithelium including gustatory papillae and has been proposed to be a marker of adult taste stem/progenitor cells. Nevertheless, this hypothesis has never been directly tested. Here, by single-color genetic lineage tracing using Sox2-CreERT2 strain, we reveal that all types of taste bud cells distributed throughout the oral epithelium are derived from stem cells that express SOX2. Short-term tracing shows that SOX2-positive taste stem cells actively supply taste bud cells. At the base of epithelium outside taste buds are distributed proliferation marker- and SOX2-positive cells. Consistently, taste stem cells identified by Lgr5 expression in the circumvallate papillae also express SOX2. Together, taste stem cells distributed in oral epithelia express SOX2.

A high Q factor film bulk acoustic resonator operating in thickness shear mode excited by a lateral field is described in this paper. The influence of electrode parameters on the resonator performance is studied by the finite element method. The results showed that three key electrode parameters, including the gap, length and width, played important roles in the optimization of the resonator performance. The highest Q factor of up to 643 was obtained when the parallel electrodes were designed to be 100 µm × 10 µm with the electrode gap of 10 µm. Based on the simulation results, the AlN-based film bulk acoustic resonator with a solidly mounted structure was fabricated. The testing results showed that the real device operated at the resonance frequency of 1.94 GHz with the Q factor of 405 in air, 216 in water and 102 in phosphate buffered saline solution.

Nanosize titanium dioxide is used in water and air decontamination and in numerous home appliances and products designed for direct human use. However, the impact of nanoparticle on biological system is not known to us. Therefore, it is our urgent and primary task to ascertain the information about safety and potential hazards of products derived from nanomaterial to the health of mankind.We made use of MTT, bromodeoxyuridine (BrdU), and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays to testify the biological impact of nanosize TiO2 on olfactory bulb neurons cultured in vitro.In this article, we elucidate the cytotoxicity of titanium dioxide to olfactory bulb neurons on cellular and molecular level. We come to a conclusion that nanosize titanium dioxide causes neuronal apoptosis, and it also down-regulate the expression of olfactory marker protein (OMP) and tyrosine hydroxylase (TH).These results show that a relationship between nanoparticle exposure and pathogeny of neurodegenerative diseases may exist.

Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and its homologs (e.g., Lgr6) mark adult stem cells in multiple tissues. Recently, we and others have shown that Lgr5 marks adult taste stem/progenitor cells in posterior tongue. However, the regenerative potential of Lgr5-expressing (Lgr5(+)) cells and the identity of adult taste stem/progenitor cells that regenerate taste tissue in anterior tongue remain elusive. In the present work, we describe a culture system in which single isolated Lgr5(+) or Lgr6(+) cells from taste tissue can generate continuously expanding 3D structures ("organoids"). Many cells within these taste organoids were cycling and positive for proliferative cell markers, cytokeratin K5 and Sox2, and incorporated 5-bromo-2'-deoxyuridine. Importantly, mature taste receptor cells that express gustducin, carbonic anhydrase 4, taste receptor type 1 member 3, nucleoside triphosphate diphosphohydrolase-2, or cytokeratin K8 were present in the taste organoids. Using calcium imaging assays, we found that cells grown out from taste organoids derived from isolated Lgr5(+) cells were functional and responded to tastants in a dose-dependent manner. Genetic lineage tracing showed that Lgr6(+) cells gave rise to taste bud cells in taste papillae in both anterior and posterior tongue. RT-PCR data demonstrated that Lgr5 and Lgr6 may mark the same subset of taste stem/progenitor cells both anteriorly and posteriorly. Together, our data demonstrate that functional taste cells can be generated ex vivo from single Lgr5(+) or Lgr6(+) cells, validating the use of this model for the study of taste cell generation.

Objective.The prevalence and significance of treatment resistance and relapse in patients from China with antineutrophil cytoplasmic antibody-associated (ANCA) disease are poorly understood.Methods.A total of 98 patients with ANCA vasculitis, diagnosed between January 2003 and December 2009 in the China-Japan Friendship Hospital, were enrolled in this retrospective study.Results.Fifteen patients (15.3%) were categorized as having cytoplasmic and/or proteinase 3 (PR3) ANCA and 83 patients (84.7%) had perinuclear and/or myeloperoxidase (MPO) ANCA. After the induction phase treatment, the disease was resistant to therapy in 24 (25%) of the patients. A response to initial treatment occurred in 74 patients (75%). Of these 74 patients, remission was achieved and sustained with or without maintenance therapy in 41 patients (55%). Multivariable logistic regression models revealed that female sex was a statistically significant predictor of treatment resistance (OR 2.85; 95% CI: 1.06–2.86; p = 0.036). Additionally, elevated serum creatinine level, with each increment of 150 μmol/l, predicted resistance (p = 0.002). Among the 74 patients where remission was achieved, Cox proportional hazards models detected that those with PR3 ANCA were 1.31 times more likely to experience a relapse than were patients with MPO ANCA (95% CI: 1.01–5.35; p = 0.0001). Lung involvement was associated with an increased risk of relapse (HR 1.87; 95% CI: 1.12–4.35; p = 0.014). Although not significant, advanced age tended to be associated with relapse (p = 0.08).Conclusion.Our findings highlight the important effect of female sex and severity of renal disease at presentation as predictors of treatment resistance, and PR3 ANCA and lung involvement as predictors of relapse.

The outcome and the therapy of patients with diabetes mellitus (DM), diabetic nephropathy (DN), and non-diabetic renal disease (NDRD) are quite different, so the differential diagnosis is of considerable importance. To evaluate the usefulness of renal biopsy in type 2 diabetic patients, we examined the relationship between the clinical parameters and the histopathological findings in different age groups. Renal biopsy specimens and clinical and laboratory data from 216 patients with type 2 DM were evaluated. According to their age, three groups were defined: 17–35 years (group I), 36–59 years (group II), and more than 60 years (group III). The study showed that, beside the duration of diabetes, other clinical parameters were not significantly different between the three groups. Chronic nephritic syndrome was the most common clinical manifestation in group I (44.1 %) and in group II (34.0 %). Among patients in group III, we found a high prevalence of chronic renal failure (34.3 %) and nephrotic syndrome (28.6 %). Consistent with the clinical manifestations, IgA nephropathy was the most common pathologic finding in group I (29.4 %) and in group II (34.7 %), whereas the most frequent abnormalities in group III were membranous nephropathy (25.7 %) and tubulointerstitial lesions (14.3 %). Overall, among these patients, 14 cases were diagnosed with DN (6.5 %), 179 with NDRD (82.9 %), while 23 had concurrent DN and NDRD (10.7 %). Our results indicated that the clinical manifestations and pathologic findings in type 2 diabetic patients in different age groups have different features. This study emphasized the usefulness of renal biopsy for determining the pattern of renal damage and thus for the overall management of type 2 diabetic patients.

Objectives Glioma is the most common brain tumor in central nervous system. Traditional therapies are not effective to cure this disease. Experimental evidence indicates that the 67 kDa elastin-laminin receptor (67LR) subunit is a high-affinity non-integrin laminin-binding protein that is over-expressed on the tumor cell surface in a variety of human carcinomas, and directly correlates with a higher proliferation rate of malignant cells and tendency to metastasise. However, little is known of the expression and function of 67LR in glioma cells. Methods In this study, we estimated whether 67LR was constitutively over-expressed in high-grade astrocytomas by immunohistochemical staining and Western blotting, and investigated the role of a low level of 67LR expression in glioma cell line-U251 by constructing an interfering RNA expression plasmid. Results The results showed that the 67LR had an enhanced over-expression in high-grade astrocytomas against normal brain tissues samples, and that the migratory activity of glioma cells was reduced after the down-regulation of the 67LR gene by RNAi. Discussion It was hypothesized that a low level of 67LR expression could reduce migratory activity of glioma cells, which further proved that 67LR played an important role in glioma invasion by mediating tumor cell functions leading to sarcomata. This study provided a new alternative to gene therapy for glioma treatment.

High-grade astrocytomas are among the most intractable types of cancers and are often fatal. Previous studies have suggested that high-grade astrocytomas may adopt the self-renewal and migration properties of neural stem cells (NSCs) to proliferate and spread by expressing the stem cell-specific genes. However, despite a few common molecules being documented, the molecular basis underlying these similarities remains largely unknown. To have a better understanding of the stem cell characteristics of high-grade astrocytomas, we performed the study to identify the stem cell-resembling gene expression profile in high-grade astrocytomas. cDNA microarray analysis was used to detect the differentially expressed genes of isolated human high-grade astrocytomas versus their peritumoral tissue counterparts, and the identification of stem cell-resembling genes was approached by comparing the high-grade astrocytomas-specific gene expression profile with that of NSCs identified by our previous study and other groups. We identified more than 200 high-grade astrocytomas-specific genes in this study, and near 10% genes or gene families of them exhibited similar up or down expression patterns as in NSCs. Further analysis indicated that these genes were actively involved in cell proliferation, adhesion, migration, and metastasis. This study revealed a list of stem cell-specific genes in high-grade astrocytomas, which was likely to have critical roles in determining the "stem" characteristics of high-grade astrocytomas.