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To elucidate the influence of various broad bean raw materials on the quality of Pixian broad bean chili paste (PBCP), an investigation was undertaken utilizing five distinct cultivars of broad beans to prepare PBCP and physicochemical indices, free amino acids and volatile profiles were analyzed. The results revealed notable disparities (P1, a total of 11 key flavor substances were screened, with most of these substances being relatively abundant in PBCPs fermented by CH23 and YD. Overall, qualities of PBCPs fermented by CH18, CH23, and TCX were better than that fermented by SCZG and YD. However, defect was observed in the physical appearance of PBCP fermented by TCX. Consequently, CH18 and CH23 were more appropriate for the processing of PBCP. This research underscores the significance of broad bean cultivar as an instrumental factor driving the variances in physicochemical and sensory attributes of PBCP, and it thereby advocates the selection of raw material to improve the quality of final products.

Abstract Idiopathic congenital nystagmus (ICN) manifests as involuntary and periodic eye movements. To identify the genetic defect associated with X-linked ICN, Whole Exome Sequencing (WES) was conducted in two affected families. We identified two frameshift mutations in FRMD7, c.1492dupT/p.(Y498Lfs*15) and c.1616delG/p.(R539Kfs*2). Plasmids harboring the mutated genes and qPCR analysis revealed mRNA stability, evading degradation via the NMD pathway, and corroborated truncated protein production via Western-blot analysis. Notably, both truncated proteins were degraded through the proteasomal (ubiquitination) pathway, suggesting potential therapeutic avenues targeting this pathway for similar mutations. Moreover, we conducted a comprehensive analysis, summarizing 140 mutations within the FRMD7 gene. Our findings highlight the FERM and FA structural domains as mutation-prone regions. Interestingly, exons 9 and 12 are the most mutated regions, but 90% (28/31) mutations in exon 9 are missense while 84% (21/25) mutations in exon 12 are frameshift. A predominant occurrence of shift code mutations was observed in exons 11 and 12, possibly associated with the localization of premature termination codons (PTCs), leading to the generation of deleterious truncated proteins. Additionally, our conjecture suggests that the loss of FRMD7 protein function might not solely drive pathology; rather, the emergence of aberrant protein function could be pivotal in nystagmus etiology. We propose a dependence of FRMD7 protein normal function primarily on its anterior domain. Future investigations are warranted to validate this hypothesis.

In order to explore the optimal design method of slope morphology of open-pit coal mine, the south slope of Heishan Open-pit Mine was taken as an engineering example. Based on the simplified Bishop method and the theory of slope morphology effect, the slope with different concave and convex degrees under the two-dimensional perspective was designed, and the stability evaluations are carried out to obtain the better slope morphology. Based on the strength reduction method, the numerical simulation method is used to simulate the deformation process of the better slope morphology under the action of three-dimensional retaining. By analyzing the deformation characteristics, the optimal slope morphology is obtained by further improving the concave and convex degree of the slope surface. The results show that the slope morphology with better concave and convex degree under the two-dimensional design conditions is obtained. Due to the limitation of local slope stability, only two groups of composite steps can be arranged from the bottom to the top below the level of + 2385 m in the southern slope. The overall stability coefficient of the slope is 1.344, and the local stability coefficient is 1.204. Under the condition of three-dimensional design, the local and overall stability of the slope is improved under the influence of the support from the internal dump and the horizontal mining working side, and there is further morphological optimization space. On the basis of the better shape, the optimal slope shape can be obtained by adding a group of combined steps to local steepen the slope section below + 2430 m level. In the process of numerical simulation , the deformation speed presented is relatively slow after entering the variable speed stage before critical instabilityand the final strength reduction coefficient is 1.20. Under the premise that the surface boundary and bottom boundary are unchanged, the optimal slope morphology can ensure the slope safety and save about 3.84 million cubic meters of rock stripping in the first mining area.

Coptis chinensis Franch. (Huanglian in Chinese) is an important economic crop with medicinal value. Its rhizome has been used as a traditional herbal medicine for thousands of years in Asia. Protoberberine alkaloids, as the main bioactive component of Coptis chinensis, have a series of pharmacological activities. However, the protoberberine alkaloids content of C. chinensis is relatively low. Understanding the molecular mechanisms affecting the transcriptional regulation of protoberberine alkaloids would be crucial to increase their production via metabolic engineering. WRKY, one of the largest plant-specific gene families, regulates plant defense responses via the biosynthesis of specialized metabolites such as alkaloids. Totally, 41 WRKY transcription factors (TFs) related to protoberberine alkaloid biosynthesis were identified in the C. chinensis genome and classified into three groups based on phylogenetic and conserved motif analyses. Three WRKY genes (CcWRKY7, CcWRKY29, and CcWRKY32) may regulate protoberberine alkaloid biosynthesis, as suggested by gene-specific expression patterns, metabolic pathways, phylogenetic, and dual-luciferase analysis. Furthermore, the CcWRKY7, CcWRKY29, and CcWRKY32 proteins were specifically detected in the nucleus via subcellular localization. This study provides a basis for understanding the regulatory mechanisms of protoberberine alkaloid biosynthesis and valuable information for breeding C. chinensis varieties.

The coal hydrogen production process requires high-temperature steam as a reactant. Coal-fired boilers are usually used to provide high-temperature steam. The ammonia-based desulphurization process is an effective technology to remove SO2 in the coal-fired flue gas. However, the mass transfer coefficient of SO2 in such an engineered process is not readily available in the literature. In this paper, experiments were carried out to investigate the mass transfer process of SO2 absorption. Combing calculating the air and liquid contact area of the droplet and liquid membrane on the tower wall, the mass transfer coefficient contain parameters pH, gas flue rate and liquid to gas ratio was proposed. The comparison results show that the calculated SO2 mass transfer rate agrees well with the measured data. The relative error of the calculated and experimental values was less than ±20%. This proposed mass transfer coefficient appears to be beneficial for the design and operation of ammonia-based desulfurization FGD system.

Traditional organic amines exhibit inferior desorption performance and high regeneration energy consumption. The implementation of solid acid catalysts presents an efficacious approach to mitigate regeneration energy consumption. Thus, investigating high-performance solid acid catalysts holds paramount importance for the advancement and implementation of carbon capture technology. This study synthesized two Lewis acid catalysts via an ultrasonic-assisted precipitation method. A comparative analysis of the catalytic desorption properties was conducted, encompassing these two Lewis acid catalysts and three precursor catalysts. The results demonstrated that the CeO2-γ-Al2O3 catalyst demonstrated superior catalytic desorption performance. Within the desorption temperature range of 90 to 110 °C, the average desorption rate of BZA-AEP catalyzed by the CeO2-γ-Al2O3 catalyst was 87 to 354% greater compared to the desorption rate in the absence of the catalyst, and the desorption temperature can be reduced by approximately 10 °C. A comprehensive analysis of the catalytic desorption mechanism of the CeO2-γ-Al2O3 catalyst was conducted, and indicated that the synergistic effect of CeO2-γ-Al2O3 conferred a potent catalytic influence throughout the entire desorption process, spanning from the rich solution to the lean solution.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with a very high fatality rate. Our goal in this study is to find a reliable lipid metabolism-related signature associated with prognostic significance for HCC. In this study, HCC lipid metabolism-related molecular subtype analysis was conducted based on the 243 lipid metabolism genes collected from the Molecular Signatures Database. Several significant disparities in prognosis, clinicopathological characteristics, and immune and ferroptosis-related status were found across the three subtypes, especially between C1 and C3 subgroups. Differential expression analysis yielded 57 differentially expressed genes (DEGs) between C1 and C3 subtypes. GO and KEGG analysis was employed for functional annotation. Three of 21 prognostic DEGs (CXCL8, SLC10A1, and ADH4) were finally selected through machine-learning-based discovery and validation strategy. The risk score = (0.103) × expression value of CXCL8 + (−0.0333) × expression value of SLC10A1 + (−0.0812) × expression value of ADH4. We used these three to construct a HCC prognostic risk model, which stratified the patients of the validation cohort into two risk subtypes with significantly different overall survival. Our work provides possible significance of the lipid metabolism-associated model in stratifying patient prognosis and its feasibility to guide therapeutic selection.

Ferritinophagy is associated with tumor occurrence, development, and therapy effects. Ferritinophagy and ferroptosis are regulated by iron metabolism and are closely connected. LC3 protein is a key protein in autophagy. Following the binding of NCOA4 to FTH1, it links to LC3Ⅱ in lysosomes, a symbol of ferritinophagy. A ferritinophagy’s inducer is likely to open new avenues for anticancer medication research and development. In this study, we discovered that caryophyllene oxide has a substantial inhibitory effect on HCCLM3 and HUH7 cells, by regulating the level of cellular oxidative stress, and the levels of autophagy and iron metabolism in HCCLM3 and HUH7 cells, leading to a ferritinophagy-related phenomenon. Furthermore, the results of T-AOC, DPPH free radical scavenging rate, and hydroxyl radical inhibition indicated that caryophyllene oxide can inhibit cell anti-oxidation. The examination of the ferritinophagy-related process revealed that caryophyllene oxide promotes the production and accumulation of intracellular reactive oxygen species and lipid peroxidation. NCOA4, FTH1, and LC3Ⅱ were found to be targeted regulators of caryophyllene oxide. Caryophyllene oxide regulated NCOA4, LC3 Ⅱ, and FTH1 to promote ferritinophagy. In vivo, we discovered that caryophyllene oxide can lower tumor volume, significantly improve NCOA4 and LC3 protein levels in tumor tissue, and raise Fe2+ and malondialdehyde levels in serum. The compound can also reduce NRF2, GPX4, HO-1, and FTH1 expression levels. The reduction in the expression levels of NRF2, GPX4, HO-1, and FTH1 by caryophyllene oxide also inhibited GSH and hydroxyl radical’s inhibitory capacities in serum, and promoted iron deposition in tumor tissue resulting in the inhibition of tumor growth. In summary, our study revealed that caryophyllene oxide mostly kills liver cancer cells through ferritinophagy-mediated ferroptosis mechanisms. In conclusion, caryophyllene oxide may be used as a ferritinophagy activator in the field of antitumor drug research and development.

To find suitable absorbents for ship-based carbon capture, the absorption and desorption properties of four mixed aqueous amines based on BZA were investigated, and the results indicated that BZA-AEP had the best absorption and desorption performance. Then, the absorption and desorption properties of different mole ratios of BZA-AEP were tested. The results showed that the average CO2 absorption rate had the highest value at the mole ratio of BZA to AEP of three. The average CO2 desorption rate had the maximum value at the mole ratio of BZA to AEP of one. Three fitted models of the absorption and desorption performance of BZA-AEP based on the test data were obtained. The p-values of all three models were less than 0.0001. Considering the performance and material cost, the BZA-AEP mole ratio of 1.5 is more appropriate for ship carbon capture. Compared with MEA, the average CO2 absorption rate increased by 48%, the CO2 desorption capacity increased by 120%, and the average CO2 desorption rate increased by 161%.

Abstract Background Recently, it has been reported that miRNA is involved in pterygium, however the exact underlying mechanism in pterygium is unrevealed and require further investigation. Methods The differential expression of miRNA in pterygium was profiled using microarray and validated with quantitative real-time polymerase chain reaction (qRT-PCR). Human conjunctival epithelial cells (HCEs) were cultured and treated with transforming growth factor β (TGF-β) and epidermal growth factor (EGF) and transfected with miR-199a-3p/5p mimic and inhibitor. Markers of epithelial-mesenchymal transition (EMT) in HCEs were detected using western blot and immunohistochemistry. Cell migration ability was determined using wound healing and transwell assay, while apoptosis was determined by flow cytometry. The target genes of miR-199a were confirmed by the dual-luciferase reporter assay. Results TGF-β and EGF could induced EMT in HCEs and increase miR-199a-3p/5p but suppress target genes, DUSP5 and MAP3K11. With the occurrence of EMT, cell migration ability was enhanced, and apoptosis was impeded. Promoting miR-199a-3p/5p expression could induce EMT in HCEs without TGF-β and EGF, while suppressing miR-199a-3p/5p could inhibit EMT in TGF-β and EGF induced HCEs. In a word, TGF-β and EGF induced EMT could be regulated with miR-199a-3p/5p-DUSP5/MAP3K11 axes. The validated results in tissues showed that, compared with control conjunctival tissues, miR-199a-3p/5p were more overexpressed in pterygium, while DUSP5/MAP3K11 were lower expressed. In addition, bioinformatics analysis indicated the miR-199a-3p/5p-DUSP5/MAP3K11 was belong to MAPK signalling pathway. Conclusions TGF-β and EGF induce EMT of HCEs through miR-199a-3p/5p-DUSP5/MAP3K11 axes, which explains the pathogenesis of EMT in pterygium and may provide new targets for pterygium prevention and therapy.

The evolution of volatile compounds during the ripening of Chinese horse bean-chili-paste (CHCP) was investigated in this study. GC×GC-TOF/MS allowed an identification of 748 volatiles in three CHCP samples, respectively, ripened for 3 months (M3), 12 months (M12) and 24 months (M24), and it showed that a longer ripening resulted in a richer diversity of the volatiles. In addition, M3 contained more aldehydes and organic acids in content and M12 had more alcohols, ketones, and esters, while M24 was abundant in heterocyclics. A total of 69 among the 748 volatiles were discriminated as the key flavor compounds of CHCP by method of Fisher ratio together with odor activity value and flavor dilution, including 12 alcohols, 9 aldehydes, 4 ketones, 5 organic acids, 16 esters, 4 phenols, 6 sulfur-containing compounds, and 13 heterocyclics. Further, principal component analysis suggested that some key aldehydes contributed the flavor of M3, while some key alcohols, esters and heterocyclics existed in M12, and some key phenols and heterocyclics were in M24. Varying of the key flavor volatiles during CHCP ripening gave it different fragrance configurations. Results presented details for the volatile profiles of CHCP during the natural ripening period, beneficial to shorten fermentation time by functional microorganisms, and could enrich the desire flavors.

A great deal of modern catalytic research orients around the architecturally designed bio-engineered catalysts. In this context, we have adorned Cu NPs over pectin encapsulated Fe3O4 NPs. The Cu NPs were generated following a biogenic green pathway over the core-shell type nanocomposite promoted by Mentha Pulegium flower extract as natural reducing/stabilizing agent. The as-synthesized nanocomposite was meticulously characterized by using a wide range of physicochemical techniques like FT-IR, FESEM, TEM, EDX, elemental mapping, VSM, XRD and ICP-OES analysis. The catalyst was explored in the synthesis of diversely substituted 1H-tetrazoles via three component coupling reaction (MCR), under solvent-less conditions affording high to excellent yields. Heterogeneity of the catalyst was measured through its excellent reusability, hot-filtration test and leaching study. The nanocomposite was also explored biologically in the anticancer assays. In the cytotoxicity and anti-human colon carcinoma studies, the nanocomposite was treated to colorectal adenocarcinoma (HT-29) cell line following MTT assay. The cell viability of malignant colon cell line reduced dose-dependently in the presence of Cu/Pectin@Fe3O4 nanocomposite. IC50 values of the nanocomposite were observed to be 1450.84 μg/mL against HT-29 cell line. The outstanding results showed by the developed nanocomposite, could be highly promising in cancer management in near future.

The hemagglutinin (HA) surface glycoprotein is triggered by endosomal low pH to cause membrane fusion during influenza A virus (IAV) entry yet must remain sufficiently stable to avoid premature activation during virion transit between cells and hosts. HA activation pH and/or virion inactivation pH values less than pH 5.6 are thought to be required for IAV airborne transmissibility and human pandemic potential. To enable higher-throughput screening of emerging IAV strains for "humanized" stability, we developed a luciferase reporter assay that measures the threshold pH at which IAVs are inactivated. The reporter assay yielded results similar to TCID50 assay yet required one-fourth the time and one-tenth the virus. For four A/TN/09 (H1N1) HA mutants and 73 IAVs of varying subtype, virion inactivation pH was compared to HA activation pH and the rate of inactivation during 55°C heating. HA stability values correlated highly with virion acid and thermal stability values for isogenic viruses containing HA point mutations. HA stability also correlated with virion acid stability for human isolates but did not correlate with thermal stability at 55°C, raising doubt in the use of supraphysiological heating assays. Some animal isolates had virion inactivation pH values lower than HA activation pH, suggesting factors beyond HA stability can modulate virion stability. The coupling of HA activation pH and virion inactivation pH, and at a value below 5.6, was associated with human adaptation. This suggests that both virologic properties should be considered in risk assessment algorithms for pandemic potential.

BackgroundNowadays, researchers are leveraging the mRNA-based vaccine technology used to develop personalized immunotherapy for cancer. However, its application against glioma is still in its infancy. In this study, the applicable candidates were excavated for mRNA vaccine treatment in the perspective of immune regulation, and suitable glioma recipients with corresponding immune subtypes were further investigated.MethodsThe RNA-seq data and clinical information of 702 and 325 patients were recruited from TCGA and CGGA, separately. The genetic alteration profile was visualized and compared by cBioPortal. Then, we explored prognostic outcomes and immune correlations of the selected antigens to validate their clinical relevance. The prognostic index was measured via GEPIA2, and infiltration of antigen-presenting cells (APCs) was calculated and visualized by TIMER. Based on immune-related gene expression, immune subtypes of glioma were identified using consensus clustering analysis. Moreover, the immune landscape was visualized by graph learning-based dimensionality reduction analysis.ResultsFour glioma antigens, namely ANXA5, FKBP10, MSN, and PYGL, associated with superior prognoses and infiltration of APCs were selected. Three immune subtypes IS1–IS3 were identified, which fundamentally differed in molecular, cellular, and clinical signatures. Patients in subtypes IS2 and IS3 carried immunologically cold phenotypes, whereas those in IS1 carried immunologically hot phenotype. Particularly, patients in subtypes IS3 and IS2 demonstrated better outcomes than that in IS1. Expression profiles of immune checkpoints and immunogenic cell death (ICD) modulators showed a difference among IS1–IS3 tumors. Ultimately, the immune landscape of glioma elucidated considerable heterogeneity not only between individual patients but also within the same immune subtype.ConclusionsANXA5, FKBP10, MSN, and PYGL are identified as potential antigens for anti-glioma mRNA vaccine production, specifically for patients in immune subtypes 2 and 3. In summary, this study may shed new light on the promising approaches of immunotherapy, such as devising mRNA vaccination tailored to applicable glioma recipients.

The plasma-catalytic oxidation of soot was studied over zeolite-supported vanadium catalysts, while four types of zeolites (MCM-41, mordenite, USY and 5A) were used as catalyst supports. The soot oxidation rate followed the order of V/MCM-41 > V/mordenite > V/USY > V/5A, while 100% soot oxidation was achieved at 54th min of reaction over V/MCM-41 and V/mordenite. The CO2 selectivity of the process follows the opposite order of oxidation rate over the V/M catalyst. A wide range of catalyst characterizations including N2 adsorption–desorption, XRD, XPS, H2-TPR and O2-TPD were performed to obtain insights regarding the reaction mechanisms of soot oxidation in plasma-catalytic systems. The redox properties were recognized to be crucial for the soot oxidation process. The effects of discharge power, gas flow rate and reaction temperature on soot oxidation were also investigated. The results showed that higher discharge power, higher gas flow rate and lower reaction temperature were beneficial for soot oxidation rate. However, these factors would impose a negative effect on CO2 selectivity. The proposed “plasma-catalysis” method possessed the unique advantages of quick response, mild operation conditions and system compactness. The method could be potentially applied for the regeneration of diesel particulate filters (DPF) at low temperatures and contribute to the the emission control of diesel engines.

Abstract Background Tuberous sclerosis complex (TSC), belongs to autosomal dominant genetic disorder, which affects multiple organ systems in the body, including the skin, brain, lungs, kidneys, liver, and eyes. Mutations in TSC1 or TSC2 was proved to be associated with these conditions. Methods Gene‐panel Sequence of NGS was used to detect the mutation in a Chinese family. The research further investigates whether aberrant splicing and nonsense‐mediated mRNA degradation (NMD) could serve as a mechanism cause by TSC1 mutation. MINI‐Gene assay apply by pcMINI‐TSC1wt/mut plasmids delivered in HeLa and 293T cell lines. Recombinant plasmids expressing wild‐type and mutant‐type EGFP‐TSC1 were constructed and transiently transfected into human embryonic kidney cells 293T by lipofectamine. Real‐time PCR and Western Blot were performed to analyze the expression of mRNAs and proteins of EGFP‐TSC1 and NMD factor UPF1. Results The gene test verified a novel heterozygous TSC1 frameshift mutation (TSC1 c.1550_1551del) in the proband and her mother. From MINI‐Gene assay, the agarose gel showed that both the mutant and wild‐type mRNA possess two main bands, indicating two splicing modes, named band A and B, respectively. The mutation c.1550_1551del has not produced new splicing site, but there is a selective splicing in varying degree significantly after mutation. On the contrary, function validation assay showed that cells transfected with the mutant TSC1 plasmids expressed significantly lower TSC1 in mRNAs and proteins levels, compared with the wild‐type TSC1 plasmid transfection. A translation inhibitor cycloheximide and small interfering RNA of UPF1 (siRNA‐UPF1) increased mRNA or protein expression of TSC1 significantly in cells transfected with the mutant plasmids. Conclusion Our study demonstrated that the novel TSC1 frameshift mutation (TSC1 c.1550_1551del) trigger aberrant splicing and NMD simultaneously, causing decrease of hamartin, then, leading to tuberous sclerosis complex formation.

Pandemic influenza A viruses can emerge from swine, an intermediate host that supports adaptation of human-preferred receptor-binding specificity by the hemagglutinin (HA) surface antigen. Other HA traits necessary for pandemic potential are poorly understood. For swine influenza viruses isolated in 2009–2016, gamma-clade viruses had less stable HA proteins (activation pH 5.5–5.9) than pandemic clade (pH 5.0–5.5). Gamma-clade viruses replicated to higher levels in mammalian cells than pandemic clade. In ferrets, a model for human adaptation, a relatively stable HA protein (pH 5.5–5.6) was necessary for efficient replication and airborne transmission. The overall airborne transmission frequency in ferrets for four isolates tested was 42%, and isolate G15 airborne transmitted 100% after selection of a variant with a stabilized HA. The results suggest swine influenza viruses containing both a stabilized HA and alpha-2,6 receptor binding in tandem pose greater pandemic risk. Increasing evidence supports adding HA stability to pre-pandemic risk assessment algorithms.

Abstract This paper deals with a Neumann boundary value problem in a d-dimensional box Td=(0,π)d $\mathbb{T}^{d}=(0,\pi)^{d}$ ( d=1,2,3 $d=1, 2, 3$) for a nonlinear diffusion chemotaxis model with logistic source. By using the embedding theorem, the higher-order energy estimates and bootstrap arguments, the condition of chemotaxis-driven instability and the nonlinear evolution near an unstable positive constant equilibrium for this chemotaxis model are proved. Our result provides a quantitative characterization for early spatial pattern formation on the positive constant equilibrium. Finally, numerical simulations are carried out to support our theoretical nonlinear instability results.

Electrochemical N2 reduction reaction (NRR) has been considered as a promising and green process to replace conventional Haber−Bosch process. However, the presence of sluggish reaction kinetics and competitive hydrogen evolution reaction (HER) can result in poor activity and unsatisfactory selectivity. Here, we proposed C/MoS2 catalysts by a facile ‘one-pot’ hydrothermal method. Benefiting from porous nanosphere structure, it shows outstanding charge transfer rate, which accelerates NRR kinetics. As a result, C/MoS2 exhibited a conspicuously improved NRR performance with a high Faradaic efficiency (FE) of 8.2% at −0.7 V. In addition, this electrocatalyst showed marvelous stability.

A pandemic-capable influenza virus requires a hemagglutinin (HA) surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. HA stabilization has been linked to 2009 pH1N1 pandemic potential in humans and H5N1 airborne transmissibility in the ferret model. Swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on HA stability was unknown. For over 70 contemporary swine H1 and H3 isolates, we measured HA activation pH to range from pH 5.1 to 5.9 for H1 viruses and pH 5.3 to 5.8 for H3 viruses. Thus, contemporary swine isolates vary widely in HA stability, having values favored by both avian (pH >5.5) and human and ferret (pH ≤5.5) species. Using an early 2009 pandemic H1N1 (pH1N1) virus backbone, we generated three viruses differing by one HA residue that only altered HA stability: WT (pH 5.5), HA1-Y17H (pH 6.0), and HA2-R106K (pH 5.3). All three replicated in pigs and transmitted from pig-to-pig and pig-to-ferret. WT and R106 viruses maintained HA genotype and phenotype after transmission. Y17H (pH 6.0) acquired HA mutations that stabilized the HA protein to pH 5.8 after transmission to pigs and 5.5 after transmission to ferrets. Overall, we found swine support a broad range of HA activation pH for contact transmission and many recent swine H1N1 and H3N2 isolates have stabilized (human-like) HA proteins. This constitutes a heightened pandemic risk and underscores the importance of ongoing surveillance and control efforts for swine viruses.

The earliest researches on application of GPS to earthquake monitoring and prediction in China began in 1980s, and it was limited to learn some relative technology from other countries and do some test with a few of equipments. As the improvement of software for data processing and the depreciating of hardware, several local GPS network had been gradually set up till the end of 1990s, and then more systematically GPS monitoring, data processing and its application research have been done gradually. In this paper, 3 research examples of the application of GPS to earthquake monitoring and prediction are presented.

T cell abnormalities have been reported to play an important role in pathogenesis of immune thrombocytopenia (ITP) besides specific autoantibodies towards platelet. The aim of this study was to explore the clinical importance of T lymphocyte subsets in adult patients with newly diagnosed ITP before and after first-line treatment. Elderly ITP patients were also studied and we tried to analyze the relationships between these items and therapeutic outcomes. The patients were treated with intravenous immunoglobulin (IVIG) plus corticosteroids and therapeutic responses were evaluated. As a result, compared with the controls, absolute lymphocyte counts in ITP patients decreased significantly before treatment. After treatment, lymphocyte counts restored to control level regardless of their treatment outcomes. In addition, we observed increased IgG and CD19+ cell expression and decreased CD4+/CD8+ cell ratio in both whole ITP group and elderly group before treatment. After treatment, the increased IgG and CD19+ cell expression could be reduced in both respond and non-respond group regardless of patient age, while CD4+/CD8+ cell ratio could not be corrected in non-respond ITP patients. In non-respond ITP patients, increased CD8+ cell expression was noticed and could not be corrected by first-line treatment. Furthermore, even lower NK cell expression was found in non-respond elderly patients after treatment when compared with that in controls. Our findings suggest that ITP patients usually had less numbers of peripheral lymphocytes and patients with higher levels of CD8+ cells or lower levels of CD4+/CD8+ cell ratio were less likely to respond to first-line treatment. Lower levels of NK cells made therapies in elderly ITP patients even more difficult.

ABSTRACT The efficacy of current influenza vaccines requires a close antigenic match between circulating and vaccine strains. As such, timely identification of emerging influenza virus antigenic variants is central to the success of influenza vaccination programs. Empirical methods to determine influenza virus antigenic properties are time-consuming and mid-throughput and require live viruses. Here, we present a novel, experimentally validated, computational method for determining influenza virus antigenicity on the basis of hemagglutinin (HA) sequence. This method integrates a bootstrapped ridge regression with antigenic mapping to quantify antigenic distances by using influenza HA1 sequences. Our method was applied to H3N2 seasonal influenza viruses and identified the 13 previously recognized H3N2 antigenic clusters and the antigenic drift event of 2009 that led to a change of the H3N2 vaccine strain. IMPORTANCE This report supplies a novel method for quantifying antigenic distance and identifying antigenic variants using sequences alone. This method will be useful in influenza vaccine strain selection by significantly reducing the human labor efforts for serological characterization and will increase the likelihood of correct influenza vaccine candidate selection.

The interleukin-23 (IL-23) and its receptor (IL-23R) mediate the direct antitumor activities in human hematologic malignancies including pediatric acute leukemia. Two potentially functional genetic variants (IL-23R rs1884444 T>G and rs6682925 T>C) have been found to contribute to solid cancer susceptibility. In this study, we conducted a case-control study including 545 acute myeloid leukemia (AML) patients and 1,146 cancer-free controls in a Chinese population to assess the association between these two SNPs and the risk of AML. We found that IL-23R rs1884444 TG/GG and rs6682925 TC/CC variant genotypes were associated with significantly increased risk of AML [rs1884444: adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 1.01-1.62; rs6682925: adjusted OR = 1.30, 95%CI = 1.01-1.67], compared to their corresponding wild-type homozygotes, respectively. These findings indicated that genetic variants in IL-23R may contribute to AML risk in our Chinese population.

BACKGROUND: Quantification of circulating tumor cells (CTC) is valuable for evaluation of non-small cell lung cancer (NSCLC). The sensitivity of current methods constrains their use to detect rare CTCs in early stage. Here we evaluate a novel method, ligand-targeted polymerase chain reaction (LT-PCR), that can detect rare CTCs in NSCLC patients. METHODS: CTCs were enriched by immunomagnetic depletion of leukocytes and then labeled by a conjugate of a tumor-specific ligand and an oligonucleotide. After washing off free conjugates, the bound conjugates were stripped from CTCs and then analyzed by qPCR. To evaluate the clinical utility, blood samples were obtained from 72 NSCLC patients (33 initially diagnosed and 39 on chemotherapy), 20 benign patients, and 24 healthy donors. RESULTS: Experiments with healthy blood spiked with tumor cells indicated the LT-PCR allows specific detection of CTC. The clinical study showed that the initially diagnosed patients have an average of 20.8 CTC units with metastatic diseases, 11.8 CTC units with localized diseases, and 6.0 CTC units with benign diseases. With the threshold of 8.5 CTC units, the assay can detect 80% of stage I/II, 67% of stage III, and 93% of stage IV cancer. With the benign patients and healthy donors as control group, the method can detect cancer with a sensitivity of 81.8% and a specificity of 93.2%. CONCLUSION: The LT-PCR would allow quantification of CTC in NSCLC patients at a more sensitive level, providing a potential tool for stratifying malignant lung diseases, especially at early stage.

Background: Hepatic iron overload is common in patients who have undergone hematopoietic cell transplantation (HCT) and may predispose to peri- and post-HCT toxicity. To better reveal more molecules that might be involved in iron overload-induced liver injury, we utilized proteomics to investigate differentially expressed proteins in iron overload-induced hepatocytes vs. untreated hepatocytes. Methods and Results: HH4 hepatocytes were exposed to ferric ammonium citrate (FAC) to establish an in vitro iron overload model. Differentially expressed proteins initiated by the iron overload were studied by two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS) analysis. We identified 93 proteins whose quantity statistically significantly changes under excess hepatocyte iron conditions. Gene Ontology (GO) analysis showed that these differentially expressed proteins in HH4 cells are involved in various biological process including endocytosis, response to wounding, di-, trivalent inorganic cation homeostasis, inflammatory response, positive regulation of cytokine production, and etc. Meanwhile, proteomics data revealed protein level of TLR2 and IL6ST significantly increased 7 times and 2.9 times, respectively, in iron overloaded HH4 cells. Our subsequent experiments detected that FAC-treated HH4 cells can activate IL6 expression through TLR2-mediated inflammatory responses via the NF-κB pathway. Conclusions: In this study, we demonstrated that iron overload induced hepatocytes triggering TLR2-mediated inflammatory response via NF-κB signaling pathway in HH4 cells.

Vaccinia Tian Tan (VTT) was attenuated by deletion of the TC7L-TK2L and TA35R genes to generate MVTT3. The mutant was generated by replacing the open reading frames by a gene encoding enhanced green fluorescent protein (EGFP) flanked by loxP sites. Viruses expressing EGFP were then screened for and purified by serial plaque formation. In a second step the marker EGFP gene was removed by transfecting cells with a plasmid encoding cre recombinase and selecting for viruses that had lost the EGFP phenotype. The MVTT3 mutant was shown to be avirulent and immunogenic. These results support the conclusion that TC7L-TK2L and TA35R deletion mutants can be used as safe viral vectors or as platform for vaccines.

Root hair tip growth provides a unique model system for the study of plant cell polarity. Transgenic plants expressing constitutively active (CA) forms of ROP (Rho-of-plants) GTPases have been shown to cause the disruption of root hair polarity likely as a result of the alteration of actin filaments (AF) and microtubules (MT) organization. Towards understanding the mechanism by which ROP controls the cytoskeletal organization during root hair tip growth, we have screened for CA-rop2 suppressors or enhancers using CA1-1, a transgenic line that expresses CA-rop2 and shows only mild disruption of tip growth. Here, we report the characterization of a CA-rop2 enhancer (cae1-1 CA1-1) that exhibits bulbous root hairs. The cae1-1 mutation on its own caused a waving and branching root hair phenotype. CAE1 encodes the root hair growth-related, ARM domain-containing kinesin-like protein MRH2 (and thus cae1-1 was renamed to mrh2-3). Cortical MT displayed fragmentation and random orientation in mrh2 root hairs. Consistently, the MT-stabilizing drug taxol could partially rescue the wavy root hair phenotype of mrh2-3, and the MT-depolymerizing drug Oryzalin slightly enhanced the root hair tip growth defect in CA1-1. Interestingly, the addition of the actin-depolymerizing drug Latrunculin B further enhanced the Oryzalin effect. This indicates that the cross-talk of MT and AF organization is important for the mrh2-3 CA1-1 phenotype. Although we did not observe an apparent effect of the MRH2 mutation in AF organization, we found that mrh2-3 root hair growth was more sensitive to Latrunculin B. Moreover, an ARM domain-containing MRH2 fragment could bind to the polymerized actin in vitro. Therefore, our genetic analyses, together with cell biological and pharmacological evidence, suggest that the plant-specific kinesin-related protein MRH2 is an important component that controls MT organization and is likely involved in the ROP2 GTPase-controlled coordination of AF and MT during polarized growth of root hairs.