[Consistency evaluation of multidimensional quality attributes of Atractylodis Macrocephalae Rhizoma by fusion of multi-source information].

The quality control of Chinese medicinal decoction pieces is one of the key tasks in the traditional Chinese medicine industry. In this study, multi-source information fusion was employed to fuse the data from near-infrared spectroscopy, electronic tongues, and other tests and establish an overall quality consistency evaluation method for Atractylodis Macrocephalae Rhizoma, which provided methodological support for the overall quality evaluation of Atractylodis Macrocephalae Rhizoma. The near-infrared spectroscopy information was measured in both static and dynamic states for 23 batches of Atractylodis Macrocephalae Rhizoma samples from different sources, and the electronic tongue sensory information, moisture content, and leachate content were measured. The overall quality of Atractylodis Macrocephalae Rhizoma was evaluated by multi-source information fusion. The results showed that the near-infrared spectroscopy information of 16122103, 801000509, 801000352, 701003656, HX21L01, and 160956 was different from that of other batches of Atractylodis Macrocephalae Rhizoma powder in the static state, and 701003298, 16122103, 701003656, 701003107, 801000229, and 18090404 were the different batches in the dynamic state. The moisture content showed no significant difference between batches. The leachate content in the batch 801000509 was different from that in other batches. The electronic tongue sensory information of 150721004, 151237, 160703004, HX21M01, HX21K04, HX21K01, and 601003516 was different from that of other batches. Furthermore, data layer fusion was employed to analyze the overall quality of Atractylodis Macrocephalae Rhizoma. Four batches, 150721004, HX21M01, HX21K04, and HX21K01, showed the parameters exceeding the 95% control limits and differed from the other samples in terms of the overall quality. This study integrated the information of moisture, near-infrared spectroscopy, and other sources to evaluate the quality consistency among 23 batches of Atractylodis Macrocephalae Rhizoma samples, which provides a reference for the quality consistency evaluation of Chinese medicinal decoction pieces.

Comprehensive Genomic and Transcriptomic Analysis of Sclerosing Pneumocytoma.

Sclerosing pneumocytoma is a rare and distinct lung neoplasm whose histogenesis and molecular alterations are the subject of ongoing research. Our recent study revealed that AKT1 internal tandem duplications (ITD), point mutations, and short indels were present in almost all tested sclerosing pneumocytomas, suggesting that AKT1 mutations are a major driving oncogenic event in this tumor. Although the pathogenic role of AKT1 point mutations is well established, the significance of AKT1 ITD in oncogenesis remains largely unexplored. We conducted comprehensive genomic and transcriptomic analyses of sclerosing pneumocytoma to address this knowledge gap. RNA-sequencing data from 23 tumors and whole-exome sequencing data from 44 tumors were used to obtain insights into their genetic and transcriptomic profiles. Our analysis revealed a high degree of genetic and transcriptomic similarity between tumors carrying AKT1 ITD and those with AKT1 point mutations. Mutational signature analysis revealed COSMIC signatures 1 and 5 as the prevailing signatures of sclerosing pneumocytoma, associated with the spontaneous deamination of 5-methylcytosine and an unknown etiology, respectively. RNA-sequencing data analysis revealed that the sclerosing pneumocytoma gene expression profile is characterized by activation of the PI3K/AKT/mTOR pathway, which exhibits significant similarity between tumors harboring AKT1 ITD and those with AKT1 point mutations. Notably, an upregulation of SOX9, a transcription factor known for its involvement in fetal lung development, was observed in sclerosing pneumocytoma. Specifically, SOX9 expression was prominent in the round cell component, whereas it was relatively lower in the surface cell component of the tumor. To the best of our knowledge, this is the first comprehensive investigation of the genomic and transcriptomic characteristics of sclerosing pneumocytoma. Results of the present study provide insights into the molecular attributes of sclerosing pneumocytoma and a basis for future studies of this enigmatic tumor.

Constant p.L424H Mutation in GTF2I in Micronodular Thymomas With Lymphoid Stroma: Evidence Supporting Close Relationship With Type A and AB Thymomas.

Micronodular thymoma with lymphoid stroma is a rare thymic neoplasm characterized by discrete nodules of epithelial tumor cells separated by abundant lymphoid stroma. The genetic features of micronodular thymoma with lymphoid stroma remain largely unexplored. Owing to the interference of abundant intratumoral, nonneoplastic lymphoid cells, a highly sensitive approach is necessary to study genetic changes in these tumors. In this study, we used a highly sensitive next-generation sequencing assay using the molecular barcoding Ion AmpliSeq HD technology to study the most commonly mutated genes in thymomas, including GTF2I, HRAS, NRAS, KRAS, and TP53. A total of 12 cases of micronodular thymomas with lymphoid stroma were tested, and 2 cases also had areas of type A thymoma in their tumor bed. Two micronodular thymic carcinomas with lymphoid stroma, a histological mimic of micronodular thymoma, were also included for comparison. Recurrent p.L424H mutations in GTF2I were found in all the cases of micronodular thymoma with lymphoid stroma but not in the cases of micronodular thymic carcinomas. In addition, 3 cases of micronodular thymoma with lymphoid stroma also had concomitant HRAS and/or KRAS mutations. Our study showed that p.L424H mutations in GTF2I is a constant genetic feature of micronodular thymoma with lymphoid stroma. This finding strongly suggests that micronodular thymoma with lymphoid stroma is closely related to type A and AB thymomas because they all share p.L424H mutations in GTF2I.

Genomic Profiling With Large-Scale Next-Generation Sequencing Panels Distinguishes Separate Primary Lung Adenocarcinomas From Intrapulmonary Metastases.

The distinction between different separate primary lung cancers (SPLCs) and intrapulmonary metastases (IPMs) is a challenging but clinically significant issue. Histopathology-based classification is the current practice; however, it is subjective and affected by interobserver variability. Recently, next-generation sequencing (NGS) panels have been used in lung cancer diagnostics. This study aimed to investigate the value of large-scale NGS panels for distinguishing between SPLCs and IPMs. A total of 32 patients with 69 lung adenocarcinomas were included. Comprehensive histopathologic assessments of multiple pulmonary adenocarcinomas were performed independently by 3 pathologists. The consensus of histopathologic classification was determined by a majority vote. Genomic analysis was performed using an amplicon-based large-scale NGS panel, targeting single-nucleotide variants and short insertions and deletions in 409 genes. Tumor pairs were classified as SPLCs or IPMs according to a predefined molecular classification algorithm. Using NGS and our molecular classification algorithm, 97.6% of the tumor pairs can be unambiguously classified as SPLCs or IPMs. The molecular classification was predictive of postoperative clinical outcomes in terms of overall survival (P = .015) and recurrence-free interval (P = .0012). There was a moderate interobserver agreement regarding histopathologic classification (κ = 0.524 at the tumor pair level). The concordance between histopathologic and molecular classification was 100% in cases where pathologists reached a complete agreement but only 53.3% where they did not. This study showed that large-scale NGS panels are a powerful modality that can help distinguish SPLCs from IPMs in patients with multiple lung adenocarcinomas and objectively provide accurate risk stratification.

Multisystem inflammatory syndrome (MIS-C) with SARS-CoV-2 omicron variant BA.2.38 in a four-year-old Chinese girl: A case report.

We report a severe COVID-19 complicated with MIS-C in a girl treated by the author in China, and discuss the current research status and progress in the diagnosis and therapy of MIS-C in children. The patient was a 4-year-old child previously healthy who was referred to the hospital with a complaint of fever, finally, Multisystem inflammatory syndrome was diagnosed with COVID-19.

[Effects of oral and intravenous tranexamic acid on perioperative blood loss after lumbar spinal canal decompression and fusion].

OBJECTIVE: To explore the effects of different administration methods of tranexamic acid(TXA) on the perioperative blood loss, hidden blood loss, transfusion rate and adverse reactions in lumbar spinal decompression and fusion. METHODS: Sixty patients who received lumbar spinal canal decompression and fusion from July 2019 to July 2020 were enrolled and divided into observation group and control group, with 30 cases in each group. The observation group was given 2 g TXA orally at 2 hours before operation, control group was given 1 g TXA for 5-10 min before skin incision and 6 hours after operation intravenously. The intraoperative blood loss, postoperative drainage, total blood loss, hidden blood loss, drainage tube removal time, blood transfusion rate, venous thrombosis rate, adverse event rate were recorded respectively. The changes of hemoglobin(Hb) and hematocrit (HCT) were observed before operation and 1, 3 days after operation. RESULTS: Hb and HCT at 1 and 3 days after operation were significantly improved compared with those before operation(P<0.01). However, there was no significant difference between the groups(P>0.05). There were no significant difference in amount of blood loss, postoperative drainage, total blood loss, intraoperative blood loss, hidden blood loss, postoperative drainage time, and blood transfusion rate between two groups (P>0.05). There were no venous thrombosis and adverse events occurred in both groups. CONCLUSION: During the perioperative period of lumbar spinal decompression and fusion, oral TXA and intravenous TXA have the same effect in reducing perioperative blood loss and are safe and reliable. It is recommended that oral TXA be used to save medical costs and convenience.

[Critical quality attribute characterization of big brand TCM: taste formulation optimization strategy and application of Xiaoer Ganmao Oral Liquid based on taste quality attribute].

The taste is the quality attribute for the development and production of traditional Chinese medicine(TCM). To improve the medication compliance of the big brand TCM, Xiaoer Ganmao Oral Liquid, a correlation model between the electronic tongue sensor signal value and human sensory evaluation score was established, and an optimization strategy of taste improvement for Xiaoer Ganmao Oral Liquid was developed with the key techniques of statistical experimental design. Based on the above model, the optimal formulation was determined as follows: aspartame content of 1-2 mg·mL~(-1), acesulfame-K content of 1.5-3 mg·mL~(-1), and steviol glycoside content of 1-2 mg·mL~(-1). Furthermore, the optimal formulation was verified by human sensory evaluation. Therefore, the taste of Xiaoer Ganmao Oral Liquid was improved. Taking Xiaoer Ganmao Oral Liquid as an example, the present study developed the taste formulation optimization method based on the correlation between the electronic tongue and human sensory evaluation, which is expected to provide an important reference to improve the taste of oral liquid of TCM.

Establishment of normal reference range for thromboelastography based on 17,708 cases in Beijing, China.

Background: Thromboelastography (TEG) can dynamically evaluate the interaction between platelets and coagulation cascade and the effects of other cellular components on the activities of plasma factors, to comprehensively analyze the whole process of blood coagulation and dissolution. Due to differences in both the incidence rates and the coagulation state of related diseases, many studies have highlighted the necessity of establishing the normal reference ranges for TEG for local regions. The aim of the present study was to determine the local normal reference ranges according to the TEG results of 17,708 volunteers in Beijing, to explore the coagulation characteristics related to the age and sex of the study population. Methods: Reference ranges of reaction time (R), coagulation time (K), coagulation angle (α-angle), and maximum thrombus consistency (MA) for TEG in healthy adults in Beijing were determined in the physical examination of 17,708 Beijing volunteers (5,319 women and 12,389 men). The volunteers were divided into the elderly group (≥60 years old) and young and middle-aged group (20-59 years old), and the reference ranges of each group were calculated according to sex. Results: Based on the TEG results of the 17,708 volunteers who underwent physical examination, the 95% reference ranges of R, K, α-angle, and MA for TEG in Beijing were 5.1-10 min, 1.3-3.8 min, 44.9-70.2°, and 50.4-71 min, respectively. The results of R, K, α-angle, and MA for TEG between the young and middle-aged group and the elderly group, as well as between women and men were significantly different (P<0.001). Finally, reference ranges for TEG in the young and middle-aged group and the elderly group were obtained. Conclusions: Compared with the reference standards provided by previous reagent manufacturers, the coagulation factor and fibrinogen function of TEG tend to be hypocoagulable in Beijing population. We found that the young and middle-aged group had lower coagulation activity than the elderly group, and women had higher coagulation activity than men in the same group.

[Distribution and sequestration of straw carbon in surface and deep soil aggregates under different fertilization treatments]. / ä¸åŒæ–½è‚¥æ¡ä»¶ä¸‹ç§¸ç§†ç¢³åœ¨è¡¨å±‚å’Œæ·±å±‚åœŸå£¤å›¢èšä½“ä¸­çš„åˆ†é ä¸Žå›ºå­˜.

Long-term fertilization causes the differences in water, heat, nutrients and microbial activities between topsoil and deep soil, with consequences on the decomposition and turnover of straw carbon (C) in soils. At a long-term positioning experimental station in Shenyang Agricultural University, we mixed the topsoil (0-20 cm) and deep soil (40-60 cm) samples from different fertilization treatments with 13C-labeled straw for in-situ incubation. We analyzed the content of organic C and its δ13C value in soil aggregates, compared the difference in the distribution of straw C between topsoil and deep soil aggregates, and explored the effects of fertilization on the sequestration of straw C in soil aggregates. Compared with fertilization treatments (i.e., single chemical nitrogen fertilizer application and combination of organic manure with nitrogen fertilizer application), the treatment without fertilization increased the content of straw C of <0.053 mm aggregate in the topsoil by 106.7% and that of >0.25 mm aggregate in the deep soil by 34.2%. The contribution percentage of straw C to organic C of >0.053 mm aggregate in the deep soil was about two times of that in the topsoil. About 22.6% and 11.4% of straw C was distributed into the >0.25 mm and <0.25 mm aggregates of topsoil, and about 29.4% and 8.8% of straw C was distributed into the >0.25 mm and <0.25 mm aggregates of deep soil, respectively. In conclusion, straw addition promoted the regeneration and sequestration of carbon in deep soil macroaggregates and increased the carbon sequestration potential of deep soil.

The role of conserved arginine and proline residues in enterovirus VP1 protein.

BACKGROUND: High diversity of VP1 protein among enteroviruses has been a barrier in developing universally effective antiviral drugs. To maintain structure stability during evolution, several residues of VP1 protein of enteroviruses are conserved. Therefore, investigation of highly conserved residues in VP1 protein may provide information for antiviral drug candidates against enteroviruses. METHODS: To identify highly conserved amino acid sequences of the VP1 in enterovirus genus, the Consurf and CABS-flex 2.0 web software were applied. Through the combination with secondary structure information, we focused on conserved amino acids of VP1 property analysis. RESULTS: Most conserved residues of VP1 were in the interior and interacted with VP2, VP3 and VP4 capsid proteins. Structure of EV-A71 (PDB code 4AED) showed conserved residues were at hydrophobic pocket and close to the junction between the loop and ß-barrel. Interestingly, arginine was the most common conserved residue of VP1. Proline was the second most common conserved residue and was found in the loop and ß-barrel intersection areas. VP1 protein flexibility was associated with the secondary structure. Conserved residues of VP1 in ß-barrel showed significantly low flexibility. CONCLUSION: Through large scale sequence analysis, we identified the amino acid distribution and location of conserved residues in VP1. This knowledge can be extrapolated for the Enterovirus genus and may contribute to developing the potential compound as an anti-enteroviral agent.

Comparative O-GlcNAc Proteomic Analysis Reveals a Role of O-GlcNAcylated SAM68 in Lung Cancer Aggressiveness.

O-GlcNAcylation is a reversible and dynamic post-translational protein modification catalyzed by O-GlcNAc transferase (OGT). Despite the reported association of O-GlcNAcylation with cancer metastasis, the O-GlcNAc proteome profile for cancer aggressiveness remains largely uncharacterized. Here, we report our comparative O-GlcNAc proteome profiling of two differentially invasive lung adenocarcinoma cell lines, which identified 158 down-regulated and 106 up-regulated candidates in highly invasive cells. Among these differential proteins, a nuclear RNA-binding protein, SAM68 (SRC associated in mitosis of 68 kDa), was further investigated. Results showed that SAM68 is O-GlcNAcylated and may interact with OGT in the nucleus. Eleven O-GlcNAcylation sites were identified, and data from mutant analysis suggested that multiple serine residues in the N-terminal region are important for O-GlcNAcylation and the function of SAM68 in modulating cancer cell migration and invasion. Analysis of clinical specimens found that high SAM68 expression was associated with late cancer stages, and patients with high-OGT/high-SAM68 expression in their tumors had poorer overall survival compared to those with low-OGT/low-SAM68 expression. Our study revealed an invasiveness-associated O-GlcNAc proteome profile and connected O-GlcNAcylated SAM68 to lung cancer aggressiveness.

[Critical quality attribute assessment of big brand traditional Chinese medicine: study on NIR field detection method of chemical properties of moisture in Tongren Niuhuang Qingxin Pills].

For the field detection problems of critical quality attribute(CQA) of moisture content in traditional Chinese medicine(TCM) manufacturing process, big brand TCM Tongren Niuhuang Qingxin Pills were used as the carrier, to establish a moisture content NIR field detection model with or without cellophane in real world production with use of near infrared(NIR) spectroscopy combined with stoichiometry. With the moisture content determined by drying method as reference value, the partial least square method(PLS) was used to analyze the correlation between the spectrum and the moisture reference value. Then the spectral pretreatment methods were screened and optimized to further improve the accuracy and stability of the model. The results showed that the best quantitative model was developed by the spectral data pretreatment of standard normal variate(SNV) with the latent variable factor number of 2 and 7 of Tongren Niuhuang Qingxin Pills with or without cellophane samples. The prediction coefficient of determination(R_(pre)~2) and standard deviation of prediction(RMSEP) of the model with cellophane samples were 0.765 7 and 0.157 2%; R_(pre)~2 and RMSEP of the model without cellophane samples were 0.772 2 and 0.207 8%. The NIR quantitative models of moisture content of Tongren Niuhuang Qingxin Pills with and without cellophane both showed good predictive performance to realize the rapid, accurate and non-destructive quantitative analysis of moisture content in such pills, and provide a method for the field quality control of the critical chemical attributes of moisture in the manufacturing of big brand TCM.

[Critical quality attribute assessment of big brand traditional Chinese medicine: quality control of Tongren Niuhuang Qingxin Pills in texture and sensory attributes].

Texture sensory attributes are the key items in quality control of Chinese medicinal honeyed pills. The purpose of this study is to develop a quality control method for assessing the texture sensory attributes of Chinese medicinal honeyed pills based on real-world Tongren Niuhuang Qingxin pilular masses and finished products. First, parameters of texture profile analysis(TPA) were optimized through single factor and central composite design(CCD) experiments to establish a detection method for texture sensory attri-butes of Tongren Niuhuang Qingxin Pills. The results showed that the established detection method was stable and reliable, with the optimal parameters set up as follows: deformation percentage of 70%, detection speed at 30 mm·min~(-1), and interval time of 15 s. Furthermore, 540 data points yielded form six texture sensory attributes of pills from 30 batches were subjected to multivariate statistical process control(MSPC) with Hotelling T~2 and squared prediction error(SPE) control charts to establish the quality control method of Tongren Niuhuang Qingxin Pills. This study is expected to provide a reference for improving the quality control system of Chinese medicinal honeyed pills.

Emergence of macrolide-resistant Streptococcus pyogenes emm12 in southern Taiwan from 2000 to 2019.

BACKGROUND: Group A Streptococcus (GAS) is an important pathogen causing morbidity and mortality worldwide. Surveillance of resistance and emm type has important implication to provide helpful information on the changing GAS epidemiology and empirical treatment. METHODS: To study the emergence of resistant GAS in children with upper respiratory tract infection (URTI), a retrospective study was conducted from 2000 to 2019 in southern Taiwan. Microbiological studies, including antibiotic susceptibility, were performed. GAS emm types and sequences were determined by molecular methods. The population was divided into two separate decades to analyze potential changes over time. The 1st decade was 2000-2009; the 2nd decade was 2010-2019. Multivariate analyses were performed to identify independent risk factors associated with macrolide resistance between these periods. RESULTS: A total of 320 GAS from 339 children were enrolled. Most of the children (75%) were under 9 years of age. The most common diagnosis was scarlet fever (225, 66.4%), and the frequency increased from 54.8% in the 1st to 77.9% in the 2nd decade (p < 0.0001). There was a significant increase in resistance to erythromycin and azithromycin from 18.1%, 19.3% in the 1st to 58.4%, 61.0% in the 2nd decade (p < 0.0001). This was associated with clonal expansion of the GAS emm12-ST36 which carrying erm(B) and tet(M) from 3.0% in the 1st to 53.2% in the 2nd decade (p < 0.0001). CONCLUSIONS: Significant emergence of macrolide-resistant GAS emm12-ST36 in children supports the need for continuing surveillance and investigation for the clonal virulence.

Nicotinamide Increases Intracellular NAD+ Content to Enhance Autophagy-Mediated Group A Streptococcal Clearance in Endothelial Cells.

Group A streptococcus (GAS) is a versatile pathogen that causes a wide spectrum of diseases in humans. Invading host cells is a known strategy for GAS to avoid antibiotic killing and immune recognition. However, the underlying mechanisms of GAS resistance to intracellular killing need to be explored. Endothelial HMEC-1 cells were infected with GAS, methicillin-resistant Staphylococcus aureus (MRSA) and Salmonella Typhimurium under nicotinamide (NAM)-supplemented conditions. The intracellular NAD+ level and cell viability were respectively measured by NAD+ quantification kit and protease-based cytotoxicity assay. Moreover, the intracellular bacteria were analyzed by colony-forming assay, transmission electron microscopy, and confocal microscopy. We found that supplementation with exogenous nicotinamide during infection significantly inhibited the growth of intracellular GAS in endothelial cells. Moreover, the NAD+ content and NAD+/NADH ratio of GAS-infected endothelial cells were dramatically increased, whereas the cell cytotoxicity was decreased by exogenous nicotinamide treatment. After knockdown of the autophagy-related ATG9A, the intracellular bacterial load was increased in nicotinamide-treated endothelial cells. The results of Western blot and transmission electron microscopy also revealed that cells treated with nicotinamide can increase autophagy-associated LC3 conversion and double-membrane formation during GAS infection. Confocal microscopy images further showed that more GAS-containing vacuoles were colocalized with lysosome under nicotinamide-supplemented conditions than without nicotinamide treatment. In contrast to GAS, supplementation with exogenous nicotinamide did not effectively inhibit the growth of MRSA or S. Typhimurium in endothelial cells. These results indicate that intracellular NAD+ homeostasis is crucial for controlling intracellular GAS infection in endothelial cells. In addition, nicotinamide may be a potential new therapeutic agent to overcome persistent infections of GAS.

NAD-Glycohydrolase Depletes Intracellular NAD+ and Inhibits Acidification of Autophagosomes to Enhance Multiplication of Group A Streptococcus in Endothelial Cells.

Group A Streptococcus (GAS) is a human pathogen causing a wide spectrum of diseases, from mild pharyngitis to life-threatening necrotizing fasciitis. GAS has been shown to evade host immune killing by invading host cells. However, how GAS resists intracellular killing by endothelial cells is still unclear. In this study, we found that strains NZ131 and A20 have higher activities of NADase and intracellular multiplication than strain SF370 in human endothelial cells (HMEC-1). Moreover, nga mutants of NZ131 (SW957 and SW976) were generated to demonstrate that NADase activity is required for the intracellular growth of GAS in endothelial cells. We also found that intracellular levels of NAD+ and the NAD+/NADH ratio of NZ131-infected HMEC-1 cells were both lower than in cells infected by the nga mutant. Although both NZ131 and its nga mutant were trapped by LC3-positive vacuoles, only nga mutant vacuoles were highly co-localized with acidified lysosomes. On the other hand, intracellular multiplication of the nga mutant was increased by bafilomycin A1 treatment. These results indicate that NADase causes intracellular NAD+ imbalance and impairs acidification of autophagosomes to escape autophagocytic killing and enhance multiplication of GAS in endothelial cells.

Exophagy of annexin A2 via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells.

Annexin A2 (ANXA2), a phospholipid-binding protein, has multiple biological functions depending on its cellular localization. We previously demonstrated that IFN-γ-triggered ANXA2 secretion is associated with exosomal release. Here, we show that IFN-γ-induced autophagy is essential for the extracellular secretion of ANXA2 in lung epithelial cells. We observed colocalization of ANXA2-containing autophagosomes with multivesicular bodies (MVBs) after IFN-γ stimulation, followed by exosomal release. IFN-γ-induced exophagic release of ANXA2 could not be observed in ATG5-silenced or mutant RAB11-expressing cells. Furthermore, knockdown of RAB8A and RAB27A, but not RAB27B, reduced IFN-γ-triggered ANXA2 secretion. Surface translocation of ANXA2 enhanced efferocytosis by epithelial cells, and inhibition of different exophagic steps, including autophagosome formation, fusion of autophagosomes with MVBs, and fusion of amphisomes with plasma membrane, reduced ANXA2-mediated efferocytosis. Our data reveal a novel route of IFN-γ-induced exophagy of ANXA2.

Targeting HSF1 leads to an antitumor effect in human epithelial ovarian cancer.

Late diagnosis and lack of specific therapeutic targets contribute to the low survival rate of patients with epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy. Therefore, the screening of diagnostic markers and the identification of therapeutic targets are urgently required. Heat shock factor 1 (HSF1) has been demonstrated to be overexpressed in certain malignancies and to be involved in tumor initiation, development, transformation and metastasis. It is believed that HSF1 is a promising candidate for antitumor therapy. However, its expression pattern and function in ovarian cancer are far from being fully elucidated. Therefore, we examined the HSF1 expression in human EOC tissues, and evaluated its carcinogenesis-promoting activity in a xenograft tumor model. Examination of HSF1 expression in human EOC tissues was performed by immunohistochemical assay using ovarian tissue blots. Specific short hairpin RNA (shRNA) against HSF1 was employed to knockdown HSF1 in SKOV3 cells. Cell proliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay; cell cycle distribution and apoptosis were determined by flow cytometric analysis. In normal ovarian tissues, HSF1 was barely detected, whereas, high expression of HSF1 was found in malignant EOC tissues, including serous, mucinous, endometrioid, and clear cell EOC tissues. Suppressed proliferative activity and intensified apoptosis were observed in HSF1-knockdown SKOV3 cells. In nude mouse xenografts, downregulation of HSF1 was found to cause reduced carinogenesis, indicating the antitumor effect induced by modulation of HSF1 against EOC. Our findings suggest that HSF1 may be considered as a potential candidate diagnostic marker of human EOC, and that modulation of HSF1 could be a promising therapeutic strategy against human EOC.

[Effect of Free Ammonia on Ammonia Escape During an Ammonia Oxidation Process].

This study used short process nitrification sludge to investigate the effect of high free ammonia (FA) on ammonia escape during ammonia oxidation. A sequencing batch reactor (SBR) was used to study the ammonia escape process under different FA concentrations. The results indicate that FA in water is usually combined with water molecules at lower FA concentrations to produce stable NH3·H2O with almost no ammonia escape. With high FA concentration (FA>687.1 mg·L-1), ammonia nitrogen is not oxidized to oxidized nitrogen (NO2--N concentration is <0.1 mg·L-1 at the end of aeration), but the total nitrogen (TN) reached 269.7 mg·L-1. Therefore, when there is a high FA concentration, NH4+-N will evaporate in the form of FA, resulting in ammonia escape. In addition, when 226.6 ≤ FA ≤ 711.8 mg·L-1, the free ammonia escape rate (FEV) grows rapidly with the increase in FA concentration.