Low-voltage stimulated denitrification performance of high-salinity wastewater using halotolerant microorganisms.

Nitrate is a common contaminant in high-salinity wastewater, which has adverse effects on both the environment and human health. However, conventional biological treatment exhibits poor denitrification performance due to the high-salinity shock. In this study, an innovative approach using an electrostimulating microbial reactor (EMR) was explored to address this challenge. With a low-voltage input of 1.2 V, the EMR reached nitrate removal kinetic parameter (kNO3-N) of 0.0166-0.0808 h-1 under high-salinities (1.5 %-6.5 %), which was higher than that of the microbial reactor (MR) (0.0125-0.0478 h-1). The mechanisms analysis revealed that low-voltage significantly enhanced microbial salt-in strategy and promoted the secretion of extracellular polymeric substances. Halotolerant denitrification microorganisms (Pseudomonas and Nitratireductor) were also enriched in EMR. Moreover, the EMR achieved a NO3-N removal efficiency of 73.64 % in treating high-salinity wastewater (salinity 4.69 %) over 18-cycles, whereas the MR only reached 54.67 %. In summary, this study offers an innovative solution for denitrification of high-salinity wastewater.

New Loss-of-Function Mutations in PCSK9 Reduce Plasma LDL Cholesterol.

BACKGROUND: Lower plasma levels of LDL (low-density lipoprotein) cholesterol (LDL-C) can reduce the risk of atherosclerotic cardiovascular disease. The loss-of-function mutations in PCSK9 (proprotein convertase subtilisin/kexin type 9) have been known to associate with low LDL-C in many human populations. PCSK9 genetic variants in Chinese Uyghurs who are at high risk of atherosclerotic cardiovascular disease due to their dietary habits have not been reported. METHODS: The study involved the whole-exome and target sequencing of college students from Uyghur and other ethnic groups in Xinjiang, China, for the association of PCSK9 loss-of-function mutations with low plasma levels of LDL-C. The mechanisms by which the identified mutations affect the function of PCSK9 were investigated in cultured cells using biochemical and cell assays. The causal effects of the identified PCSK9 mutations on LDL-C levels were verified in mice injected with adeno-associated virus expressing different forms of PCSK9 and fed a high-cholesterol diet. RESULTS: We identified 2 PCSK9 mutations-E144K and C378W-in Chinese Uyghurs with low plasma levels of LDL-C. The E144K and C378W mutations impaired the maturation and secretion of the PCSK9 protein, respectively. Adeno-associated virus-mediated expression of E144K and C378W mutants in Pcsk9 KO (knockout) mice fed a high-cholesterol diet also hampered PCSK9 secretion into the serum, resulting in elevated levels of LDL receptor in the liver and reduced levels of LDL-C in the serum. CONCLUSIONS: Our study shows that E144K and C378W are PCSK9 loss-of-function mutations causing low LDL-C levels in mice and probably in humans as well.

Research progress of quality control for the seed of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Suan-Zao-Ren) and its proprietary Chinese medicines.

ETHNOPHARMACOLOGICAL RELEVANCE: Semen Ziziphi Spinosae (SZS), the seed of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Chinese name Suan-Zao-Ren), is widely distributed in China, Laos, Myanmar, and Iran. It is a classic traditional Chinese medicine with sedative and sleeping effects. In clinical practice, there are more than 155 proprietary Chinese medicines containing SZS. However, many commercial SZS products are difficult to qualify using current methods. Moreover, there is a scarcity of quality standards for SZS in proprietary Chinese medicines. AIM OF THE STUDY: The purpose of this study was to clearly reveal the quality indicators during the entire production process of SZS and its products. MATERIALS AND METHODS: This study reviewed more than 230 articles and related books on the quality control of SZS and its proprietary Chinese medicines published over the last 40 years (from January 1979 to October 2022). Moreover, where available, information on the quality of SZS and its proprietary Chinese medicines was also collected from websites for comparison, including online publications (e.g. PubMed, CNKI, Google Scholar, and Web of Science), the information at Yaozhi website and China Medical Information Platform, along with some classic books on Chinese herbal medicine. The literature and information search were conducted using keywords such as "Suan-Zao-Ren", " Ziziphus jujuba" and "quality control", and the latest results from various databases were combined to obtain valid information. The active components, which in vivo exposure, and Q-markers were also summarized. RESULTS: The jujuboside A, jujuboside B, and spinosin were revealed as the key Q-markers for SZS. Moreover, the advancements and prospects of the quality control for SZS and its extract, proprietary Chinese medicines, health foods, and adulterants were comprehensively summarized. The high-performance liquid chromatography-UV/evaporative light scattering detection and fingerprint analysis were found to be the mainstream methods for the SZS quality control. In particular, the novel quality evaluation method based on the unit content was applied for SZS and its proprietary Chinese medicines. Significant fluctuations were found in the contents of Q-markers. Moreover, the mass transfer rule of Q-markers was comprehensively clarified based on the entire production process, including production origins, ripening time, primary process, processing, compatibility decoction/extract, and storage. Ultimately, the crushing and compatibility of SZS were found to be the key steps affecting the active components. CONCLUSIONS: In short, this study provides solid evidences to reveal quality indicators for the entire production process of developing rational quality standards for SZS and its products. Moreover, this study also provides a template quality control overview, which could be extended to other traditional Chinese medicines.

Perioperative Renin-Angiotensin System Inhibitors Improve Major Outcomes of Heart Failure Patients Undergoing Cardiac Surgery: A Propensity-Adjusted Cohort Study.

OBJECTIVE: The aim of this study was to study the association of perioperative administration of renin angiotensin system inhibitors (RASi) and clinical outcomes of patients with heart failure (HF) undergoing cardiac surgery. SUMMARY BACKGROUND DATA: It is controversial whether the perioperative RASi should be administered in HF patients undergoing cardiac surgery. METHODS: A total of 2338 patients with HF and undergoing CABG and/or valve surgeries at multiple hospitals from 2001 to 2015 were identified from STS database. After adjustment using propensity score and instrumental variable, logistic regression was conducted to analyze the influence of preoperative continuation of RASi (PreRASi) on short-term in-hospital outcomes. Independent risk factors of 30-day mortality, major adverse cardiovascular events (MACE), and renal failure were analyzed by use of stepwise logistic regression. The effects of pre- and postoperative use of RASi (PostRASi) on long-term mortality were analyzed using survival analyses. Stepwise Cox regression was conducted to analyze the independent risk factors of 6-year mortality. The relationships of HF status and surgery type with perioperative RASi, as well as PreRASi-PostRASi, were also evaluated by subgroup analyses. RESULTS: PreRASi was associated with lower incidences of 30-day mortality [ P < 0.0001, odds ratio (OR): 0.556, 95% confidence interval (CI) 0.405-0.763], stroke ( P =0.035, OR: 0.585, 95% CI: 0.355-0.962), renal failure ( P =0.007, OR: 0.663, 95% CI: 0.493-0.894). Both PreRASi ( P =0.0137) and PostRASi ( P =0.007) reduced 6-year mortality compared with the No-RASi groups. CONCLUSIONS: Pre- and postoperative use of RASi was associated with better outcomes for the patients who have HF and undergo CABG and/or valve surgeries. Preoperative continuation and postoperative restoration are warranted in these patients.

Serum CTRP9 and high-molecular weight adiponectin are associated with ischemic stroke.

BACKGROUND: C1q/TNF-related protein 9 (CTRP9) and adiponectin (APN) have beneficial metabolic regulatory and vasoprotective effects. This study explored alteration of CTRP9 and APN multimers during onset of ischemic stroke and development, to provide novel clinical and experimental basis for recognition and prevention of ischemic stroke. METHODS: There were 269 patients with ischemic stroke and 182 control subjects included in this study. Serum levels of CTRP9 and APN multimers in different disease stages were measured. RESULTS: Serum CTRP9, total APN (tAPN), and high-molecular weight (HMW) APN decreased gradually in stage I (acute stage, within 72 h of onset) of ischemic stroke and increased during stage III (11th day to one month) and stage IV (1 month after), compared to control. In the non-hyperlipidemia group, serum CTRP9, tAPN, and HMW were decreased in ischemic stroke patients compared to control (P < 0.05). Serum CTRP9 is closely related to serum tAPN and HMW (r = 0.992, 0.991). Serum CTRP9 are protective against ischemic stroke (OR = 0.400, 95% CI 0.197-0.810, P < 0.05). CONCLUSIONS: Lower serum CTRP9, tAPN, LMW, and HMW are significantly associated with increased ischemic stroke risk in non-hyperlipidemia subjects. CTRP9, tAPN, and HMW isoforms may be valuable clinical indicators for patients with ischemic stroke.

E3 ubiquitin ligase RNF5 attenuates pathological cardiac hypertrophy through STING.

Ring-finger protein 5 (RNF5) is an E3 ubiquitin ligase which is expressed in a variety of human tissues. RNF5 is involved in the regulation of endoplasmic reticulum stress, inflammation, and innate immunity and plays an important role in the occurrence and development of various tumors. However, the role of RNF5 in cardiac hypertrophy has not been reported. In this study, we found the expression of RNF5 was increased in the hearts of mice with pathological cardiac hypertrophy. The loss-of-function research demonstrated that RNF5 deficiency exacerbated cardiac hypertrophy, whereas gain-of-function studies revealed that overexpression of RNF5 had opposite effects. The stimulator of interferon genes (STING) is a signaling molecule that can activate type I interferon immunity, which can meditate inflammation and immune response in many diseases. The protein-protein interaction experiments confirmed that STING interacted with RNF5. Further studies showed that RNF5 inhibited cardiac hypertrophy by promoting STING degradation through K48-linked polyubiquitination. Therefore, we defined RNF5 as importantly regulated signaling for cardiac hypertrophy.

Effects of robotic-assisted gait training on motor function and walking ability in children with thoracolumbar incomplete spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) results in neurological dysfunction of the spinal cord below the injury. OBJECTIVE: To explore the immediate and long-term effects of robotic-assisted gait training (RAGT) on the recovery of motor function and walking ability in children with thoracolumbar incomplete SCI. METHODS: Twenty-one children with thoracolumbar incomplete SCI were randomly divided into the experimental (n = 11) and control groups (n = 10). The control group received 60 min of conventional physical therapy, and the experimental group received 30 min of RAGT based on 30 minutes of conventional physical therapy. Changes in walking speed and distance, physiological cost index (PCI), lower extremity motor score (LEMS), SCI walking index and centre-of-pressure (COP) envelope area score were observed in both groups of children before and after eight weeks of training. The primary outcome measures were the 10-metre walk test (10MWT) and six-minute walk distance (6MWD) at preferred and maximal speeds. In addition, several other measures were assessed, such as postural control and balance, lower limb strength and energy expenditure. RESULTS: Compared with control group, the self-selected walk speed (SWS), maximum walking speed (MWS), 6MWD, PCI, LEMS, COP, and Walking Index for Spinal Cord injury II (WISCI II) of experimental group were improved after treatment. The 6MWD, PCI, COP, and WISCI II after eight weeks of treatment were improved in experimental group. All indicators were not identical at three different time points when compared between two groups. Pairwise comparisons in experimental group suggested that the SWS, MWS, 6MWD, PCI, LEMS, COP, and WISCI II after treatment were higher than those before treatment. The 6MWD, LEMS, COP, and WISCI II after treatment were higher than at the one-month follow-up appointment. The SWS, PCI, LEMS, COP, and WISCI II at the eight-week follow-up appointment were improved. CONCLUSION: Robotic-assisted gait training may significantly improve the immediate motor function and walking ability of children with thoracolumbar incomplete SCI.

Sevoflurane preconditioning protects against acute MI/R injury via enhancing AdipoR1-Cav3 interaction and alleviating endoplasmic reticulum stress.

Whether and how sevoflurane preconditioning (SevoPre) exerts protection against acute myocardial ischemia/reperfusion (MI/R) injury remains elusive. We observed significant myocardial injury, as evidenced by infarct size, cardiomyocyte apoptosis, and circulating troponin-I, at 3 h of MI/R in both wildtype and adiponectin knockout mice. The injury was significantly ameliorated by SevoPre in wildtype mice, but not in adiponectin knockout mice. In wildtype mice, we found that MI/R could increase endoplasmic reticulum stress of cardiomyocytes, and impair association of adiponectin receptor 1 and ceveolin-3, both of which processes were largely restored by SevoPre. In summary, we demonstrated that significant injury had already took place at 3 h of MI/R, which could be ameliorated by SevoPre via promoting affinity of adiponectin receptor 1 and ceveolin-3, and then attenuating endoplasmic reticulum stress of cardiomyocytes.

Hyperlipidemic plasma molecules bind and inhibit adiponectin activity.

INTRODUCTION: Adiponectin is a potent vascular protective molecule. Recent findings have suggested adiponectin resistance during early diabetes. However, the molecular mechanisms responsible remain unidentified. Here, we took an unbiased approach to identify whether hyperlipidemic plasma molecules exist that bind and inhibit adiponectin function, contributing to adiponectin resistance and diabetic vascular injury. METHODS: Adult rats were randomly assigned to receive either a normal or a high-fat diet for 8 weeks. Plasma was co-immunoprecipitated with anti-APN antibody and analyzed by mass spectrometry. The APN binding molecules and their effect upon APN biological activity were determined. RESULTS: As expected, the high-fat-diet increased plasma triglyceride, total cholesterol, and low-density lipoprotein. Importantly, the circulating APN level was significantly increased at this time point. Mass spectrometry identified 18 proteins with increased APN binding in hyperlipidemic plasma, among which four proteins critical in lipid metabolism, including apolipoprotein A1 (APOA1), APOA4, APOC1, and paraoxonase 1, were further investigated. Incubating recombinant APN with APOA1 markedly (P < 0.01), and incubating with APOC1 significantly (P < 0.05), inhibited APN activity as evidenced by the reduced AMPK activation in HUVECs. APOA4 and paraoxonase 1 incubation had no effect upon APN activity. Finally, plasma APOA1 was significantly increased (P < 0.05) in hyperlipidemic plasma compared with the control plasma. CONCLUSIONS: It was demonstrated for the first time that increased APOA1 and APOC1 in hyperlipidemic plasma binds and inhibits APN activity. This result not only identifies a novel molecular mechanism responsible for adiponectin resistance during early stage diabetes, but also provides additional new insight into the diverse/controversial (protective and harmful) functions of high-density lipoprotein.

Improving the antioxidant and anti-tyrosinase activities of Stemonae Radix by solid-state fermentation with Mucor circinelloides T2-12.

Stemonae Radix, a medicinal and edible herb, has been reported to possess various pharmacological effects. In the present study, Stemonae Radix was fermented by fungi to improve the antioxidant and anti-tyrosinase activities. The results showed that Stemonae Radix fermented by Mucor circinelloides T2-12 exhibited two-folds more antioxidant and anti-tyrosinase activities than non-fermented material. The increased activity might be ascribed to the improvement of total phenolic content, hydrolyzation of glucosides and esters of phenolics and metabolism of saccharides according to ultraviolet and nuclear paramagnetic resonance spectroscopy. This paper suggested that fermenting Stemonae Radix with M. circinelloides T2-12 is effective to increase antioxidant and anti-tyrosinase effects and Stemonae Radix fermented by M. circinelloides T2-12 might be newly alternative of natural antioxidant and tyrosinase inhibitor. The present study is the first to report that pure strain fermentation processing is effective in improving the antioxidant and anti-tyrosinase activities of Stemonae Radix.

Enhanced visible light photocatalytic activity of N, F-codoped TiO2 powders with high thermal stability.

Doping non-metals onto TiO2 has been regarded as a promising way to gain a more effective photocatalyst. In this paper, N, F-codoped TiO2 was synthesized by the sol-gel method, demonstrating both high adsorption capacity and high photocatalytic activity under visible light irradiation. Samples were characterized by X-ray diffraction, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy and UV-visible diffuse reflectance spectra (UV-vis DRS). The results show that N, F-codoping can reduce the impact of calcination temperature on the structure and morphology of the sample, resulting in the sample exhibiting good thermal stability, even when the calcination temperature changes in a large range, instead of rutile, the anatase around 20 nm is the only phase in N, F-codoped samples. It can be clearly observed from the SEM images that N, F-codoped samples calcined at different temperatures are in the state of scattered particles with small size and good dispersed property. And it is vivid that the absorption intensity of N, F-codoped TiO2 samples in the visible light range increases substantially in DRS. According to the result of photocatalytic activity experiment, N, F-codoped TiO2 samples calcined at 973 K exhibited the highest degradation rate for Methylene Blue.

[Expression and Clinical Significance of Leukemia Stem Cell Antigen in Acute Myeloid Leukemia].

OBJECTIVE: To analyze the expression characteristics of leukemia stem cell (LSC) antigen in acute myeloid leukemia (AML) and to explore the correation of LSC-specific antigens with the subtypes, cytogenetics and clinical efficacy of AML. METHODS: A total of 61 newly diagnosed patients with AML (except M3) hospltalized in Department of Hematology of our hopital were selected from January 2013 to March 2016. The immun phenotypes and expression of Tim-3, CD96 and CD123 on leucamia cells were detected by direct immunofluorescenct flow cytometry. 61 patients were divided into positive expression and megative expression groups according to expression of Tim-3, CD96 and CD123; the correlation of LSC antigen expression level with high WBC count, chromosome and therapeutic efficacy was analyzed. RESULTS: Among 61 newly diagnosed patients with AML (except M3), the expression rate of Tim-3, CD96 and CD123 was 52.45%, 44.26% and 55.73% respectively. The expression rates of Tim-3, CD96 and CD123 between the AML subtypes and total patients was not stetistically different (P>0.05). The high WBC count occurred more easily in AML (except MS) patients with positive expression of Tim-3, CD96 and CD123, but compared with AML patients with negative espression, the difference was not statstically significant (P>0.05). The proportion of chromosone karyotype with poor prognosis detected in patients with positive expression of Tim-3 and CD96 was higher than that in patients with negative expreesion (P<0.05); while the preoprtion of chromosome karyotype with poor prognosis detected in patients with positive and negative expression of CD123 was not significantly different (P>0.05). After 2 courses of chemotherapy, the complete remission (CR) rate in patients with positive expression of Tim-3, CD96 and CD123 was significantly lower than that in patients with negative expression of Tim-3, CD96 and CD123 (P<0.05), the comparison of OS time in patients with positive and negative expression of Tim-3 and CD96 showed the statistical difference (P>0.05), while the difference of OS time in patients with positive and negative expression of CD123 was not significant (P>0.05). CONCLUSION: The expression levels of Tim-3, CD96 and CD123 in newly diagnosed AML (except M3) sybtype patients are not significantly different form those in total patients. The high WBC count ocours more easily in patients with positive expression of Tim-3, CD96 and CD123. After 2 course of chemotherapy, the CR rate in patients with positive expression of Tim-3, CD96 and CD123 was significantly lower than that in patients with negative expression. The proportion of chromsome karyotype with poor prognosis detected in patients with positive expression of Tim-3 and CD96 is high, moreover, OS time in patients with positive expression of Tim-3 and CD96 is shorter than that in patients with negative expression.

Correlation between Histone Deacetylase 9 and Regulatory T Cell in Patients with Chronic Heart Failure.

Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide. Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are reduced in HF patients and properly expanding Tregs attenuates HF progression. Histone deacetylase (HDAC) 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases. Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs. Thus, we aim to investigate the expression of HDAC 9 in patients with chronic heart failure (CHF) and the relationship among HDAC9, Tregs and CHF. Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients. Patients with CHF were divided into two groups by heart function grade of New York Heart Association (NYHA), we found that the HDAC9 mRNA expression level in NYHA grade II-III group were lower than that in NYHA grade IV group. More importantly, the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction (LVEF), whereas positively correlated to larger left ventricular end-diastolic dimension (LVEDD) and B-type natriuretic peptide (BNP) in patients with CHF. The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF. Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.

[Transcription Factor Pax5 Promotes B-lymphomagenesis in a Promoter-Independent Manner].

OBJECTIVE: To determine whether B lymphocyte-specific transcription factor Pax5 regulates B-lympho-magenesis without direct binding to promoter. METHODS: Mouse B-lymphoma cell line myc3 and 38B9 were infected with GFP- tagged retrovirus that encodes wide type or various mutant pax5 genes. After viral infection for 48 hours, the percentage of GFP positive lymphoma cells was determined by flow cytomety. The percentage of GFP positive tumor cells was further monitored every 3 days in vitro or once the tumor was formed in vivo. Both cell cycle and apoptic cell number of GFP positive lymphoma cells were analyzed using flow cytometry. RESULTS: Similar to the infection with wild type Pax5 retrovirus, infection with Pax5 mt 1-357 and Pax5 mt 304-358 that lacks of DNA binding motif can strongly increase the percentage of GFP+ B-lymphoma cells both in vitro and in vivo (P<0.01), while infection with empty viral vector migR-GFP and Pax5 mt 1-143 containing only DNA binding motif failed to increase the percentage of GFP positive tumor cells (P>0.05). Moreover, the analysis of flow cytometry demonstrated that more B-lymphoma cells infected with wild type Pax5, Pax5 mt 1-357 and Pax5 mt 304-358 retroviruses entered S and G2/M phases in comparison with those infected with empty viral vector migR-GFP and Pax5 mt 1-143. Apoptotic rates among different groups were not significantly changed. CONCLUSION: Pax5 can promote B-lymphoma cell growth both in vitro and in vivo in a promoter-independent manner. This is mainly due to the accelerating of cell cycle rather than decreasing apoptosis. Our studies provide potential theory for restraing B-lymphomagenesis by targeting the specific Pax5 domains.

lncRNA co-expression network model for the prognostic analysis of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy with great variability of prognostic behaviors. Previous studies have reported that long non-coding RNAs (lncRNAs) play an important role in AML and may thus be used as potential prognostic biomarkers. However, thus use of lncRNAs as prognostic biomarkers in AML and their detailed mechanisms of action in this disease have not yet been well characterized. For this purpose, in the present study, the expression levels of lncRNAs and mRNAs were calculated using the RNA-seq V2 data for AML, following which a lncRNA­lncRNA co-expression network (LLCN) was constructed. This revealed a total of 8 AML prognosis­related lncRNA modules were identified, which displayed a significant correlation with patient survival (p≤0.05). Subsequently, a prognosis-related lncRNA module pathway network was constructed to interpret the functional mechanism of the prognostic modules in AML. The results indicated that these prognostic modules were involved in the AML pathway, chemokine signaling pathway and WNT signaling pathway, all of which play important roles in AML. Furthermore, the investigation of lncRNAs in these prognostic modules suggested that an lncRNA (ZNF571-AS1) may be involved in AML via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway by regulating KIT and STAT5. The results of the present study not only provide potential lncRNA modules as prognostic biomarkers, but also provide further insight into the molecular mechanisms of action of lncRNAs.

Application of Rose and Wright's algorithm in the diagnosis of lacrimal gland masses: a study of 93 cases.

OBJECTIVE: To investigate the application of Rose and Wright's algorithm in diagnosing lacrimal gland masses. DESIGN: Retrospective observational cases series. PARTICIPANTS: A total of 93 consecutive patients with primary masses within the orbital lobe of the lacrimal gland were reviewed. METHODS: Before treatment, patients' detailed history was collected verbally and all patients underwent image examination (computed tomography and magnetic resonance imaging). The clinical and radiological features of every patient were evaluated by experienced orbital surgeons. Based on Rose and Wright's criteria, patients were scored and then treated using surgery with radiotherapy and/or chemotherapy. The final diagnoses were based on the histopathologic results. Based on the histopathologic diagnosis, the data from Rose and Wright's algorithm were evaluated. RESULTS: The accuracy of Rose and Wright's algorithm for benign and malignant tumour diagnoses was 75% and 50%, respectively. The diagnostic sensitivity, specificity, and accuracy of Rose and Wright's algorithm were 64%, 93%, and 86%, respectively. The algorithm demonstrated significant accuracy in the clinicoradiological criterion in differentiating between benign tumours and malignant tumours (p < 0.05). CONCLUSIONS: Rose and Wright's algorithm has great advantages in distinguishing benign from malignant tumours within the orbital lobe of the lacrimal gland. However, the algorithm should be used with great caution because of its low diagnostic sensitivity for malignant tumours.

[The effect of rat dental papilla cells on macrophage secretion of cytokines though paracrine mechanism].

PURPOSE: To investigate the immunomodulatory effects of rat dental papilla cells (RDPCs) on lipopolysaccharide(LPS)-induced macrophages. METHODS: Dental papilla tissues from SD rats were isolated and cultured. Cells were passaged and purified using different digesting method. After osteogenic differentiation of rat dental papilla cells, mineralized nodules were assessed by Alizarin red S staining. Oil red-O staining was used to observe the lipid after adipogenic differentiation of rat dental papilla cells. The effect of rat dental papilla cells conditioned medium (RDPC-CM) on macrophages proliferation was assessed using a cell counting kit-8 (CCK-8). LPS-stimulated macrophages were treated with RDPC-CM and the level of IL-1ß, TNF-α, IL-6 and nitric oxide (NO) in the supernatants were evaluated by enzyme-linked immunosorbent assay (ELISA) and Greiss reagent. The results were analyzed by using SPSS 13.0 software package. RESULTS: RDPCs were found around dental papilla piece after 24h of cultures, the cells could be purified using different digesting methods. Aliarin red staining and Oil red-O staining certified the presence of mineralized nodules and lipid in rat dental papilla cells, respectively. CCK-8 assay results showed that the proliferation of macrophages was not affected by RDPC-CM. ELISA and Griess reagent assay revealed a significantly decreased level of TNF-α in the supernatants of LPS-stimulated macrophages upon RDPC-CM treatment compared with the control, but not the levels of IL-6, IL-1ß and NO. CONCLUSIONS: RDPC-CM inhibited the expression of TNF-α in LPS-treated macrophages, indicating that rat dental papilla cells may play a role in immunomodulatory effects.

6,7-Dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives as selective inhibitors of PI3Kα.

Twenty eight 6,7-dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives were synthesized and evaluated their biological activities as PI3K inhibitors. Biological evaluation against four human tumor cell lines revealed that most target compounds showed impressively better antiproliferative activities than that of LY294002. Among these compounds, compound 25 exhibited the most potent and selective activity for PI3Kα, with the IC50 value of 0.016µM, an approximately 30-fold increase in comparison with LY294002, it also has an increased potency of approximately 11-fold for PI3Kß. It indicated the potential of developing 6,7-dihydrobenzo[f]benzo[4,5]imidazo[1,2-d][1,4]oxazepine derivatives as the new PI3Kα selective inhibitors for tumor treatment.

Synthesis, biological evaluation and molecular modeling of 1,3,4-thiadiazol-2-amide derivatives as novel antitubulin agents.

A series of 1,3,4-thiadiazol-2-amide derivatives (6a-w) were designed and synthesized as potential inhibitors of tubulin polymerization and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 6f exhibited the most potent anticancer activity against A549, MCF-7 and HepG2 cancer cell lines with IC50 values of 0.03 µM, 0.06 µM and 0.05 µM, respectively. Compound 6f also exhibited significant tubulin polymerization inhibitory activity (IC50=1.73 µM), which was superior to the positive control. The obtained results, along with a 3D-QSAR study and molecular docking that were used for investigating the probable binding mode, could provide an important basis for further optimization of compound 6f as a novel anticancer agent.