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The structural characteristics and immunoregulatory activities of neutral heteropolysaccharide (AVRP-N) separated from the roots of Apocynum venetum L. were extensively investigated. The results showed that the weight average molecular mass (Mw) of AVRP-N was 6.430 × 10

Background Whether hepatitis B virus (HBV) infection poses risk to patients with nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era remains unclear. Methods 953 patients with non-metastatic, newly diagnosed NPC who received detection of serologic hepatitis B surface antigen (HBsAg) and treated with IMRT were retrospectively reviewed. 171 patients had HBV infection (HBsAg seropositive). Propensity score matching method (PSM) and stabilized inverse probability of treatment weighting (IPTW) were used to address confounding. The survival rates were evaluated by Kaplan-Meier analysis and the survival curves were compared by Log-rank test. Prognostic factors were explored by multivariate analysis. Results No significant survival differences were observed between HBsAg-negative group and HBsAg-positive group [5-year overall survival (OS), 87.7% vs. 83.9%, P=0.181; locoregional recurrence-free survival (LRFS), 83.5% vs. 78.3%, P=0.109; distant metastasis-free survival (DMFS), 80.2% vs. 77.9%, P=0.446; progression-free survival (PFS), 77.4% vs. 71.4%, P=0.153], consistent with the results of PSM and IPTW analysis. Further analyses revealed that HBV infection was an independent prognostic factor for poor OS [multivariate analysis; hazard ratio (HR), 3.74; 95% confidence interval (CI), 1.45–9.68; P=0.006], LRFS (HR, 2.86; 95% CI, 1.37–5.95); P=0.005] in patients with stage N1, DMFS (HR, 2.65; 95% CI, 1.15–6.09; P=0.022) and PFS (HR, 2.63; 95% CI, 1.34–5.14; P=0.005). Among HBsAg-positive patients, liver protection improved OS (90.3% vs. 77.2%; P=0.022). Conclusions HBV infection is an independent risk factor for patients with stage N1 NPC in the IMRT era. Hepatic protection may benefit the survival of HBsAg-positive patients.

Epigenetic regulation plays a crucial part in the oncogenesis and treatment of diffuse large B-cell lymphoma (DLBCL). The H3K9me3-specific histone methyltransferase SUV39H1 is a significantly epigenetic gene that promotes the progression of a variety of malignancies. However, the roles of SUV39H1 in DLBCL remain unclear. By retrieving Oncomine, GEPIA, CCLE, UALCAN, and TCGA databases, we observed that the expression of SUV39H1 was higher in DLBCL tissues than in normal and other cancer tissues. Combined with immunohistochemical validation assay, we analysed clinical characteristics of DLBCL patients. The results showed that high expression of SUV39H1 was closely associated with age over 50 years old (P=0.014) and low albumin level (P=0.015). In the prognostic analyses, DLBCL patients in GEPIA database showed that the high SUV39H1 expression group had a lower disease-free survival (DFS) rate than the low SUV39H1 expression group (P=0.035). Finally, we discovered that expressions of CD86+ and CD163+ macrophages have high correlations with SUV39H1+ in DLBCL tissues(with P=0.037 and P=0.045,respectively). SUV39H1-associated macrophages may downregulate T lymphocyte subsets, especially Treg cells in DLBCL(P=0.003). In summary, SUV39H1 might be not only a potential target for the epigenetic therapy and immunotherapy of DLBCL, but also a clinical indicator for doctors to evaluate the trend of disease development.

Objective. To identify fatty acid metabolism-related biomarkers of aortic valve calcification (AVC) using bioinformatics and to research the role of immune cell infiltration for AVC. Methods. The AVC dataset was retrieved from the Gene Expression Omnibus database. R package is used for differential expression genes analysis and weighted gene coexpression analysis. The differentially coexpressed genes were identified by the Venn diagram, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially coexpressed genes. Functions closely related to AVC were identified by GO and KEGG enrichment analyses of differentially coexpressed genes. Genes related to fatty acid metabolism were retrieved from the Molecular Signatures Database (MSigDB) database. After removing duplicate genes, least absolute shrinkage and selection operator (LASSO) regression analysis, support vector machine recursive feature elimination (SVM-RFE), and random forest were applied to recognize biomarkers related to fatty acid metabolism in AVC. The CIBERSORT tool was used to analyze infiltration of immune cells in normal and AVC samples. Correlations between biomarkers and immune cells were calculated. Finally, HIBCH-related pathway was predicted by single-gene gene set enrichment analysis (GSEA). Results. 2416 differentially expressed genes and one coexpression module were identified. A total of 1473 differentially coexpressed genes were acquired. GO and KEGG enrichment analyses demonstrated that differentially coexpressed genes were closely related to fatty acid metabolism. LASSO regression analysis, SVM-REF, and random forest revealed that 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) was a biomarker of fatty acid metabolism-related genes in AVC. Significant high levels of memory B cells were found in AVC than normal samples, while activated natural killer (NK) cells were significantly low in AVC than normal samples. A significantly positive relevance was observed between HIBCH and activated NK cells, regulatory T cells, monocytes, naïve B cells, activated dendritic cells, resting memory CD4 T cells, resting NK cells, and CD8 T cells. A significantly negative relevance was observed between HIBCH and activated memory CD4 T cells, memory B cells, neutrophils, gamma delta T cells, M0 macrophages, and plasma cells. The single-gene GSEA results suggest that HIBCH may work through the inhibition of multiple immune-related pathways. Conclusion. HIBCH is closely relevant to immune cell infiltration in AVC and could be applied as a diagnostic marker for AVC.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy with a complex tumor ecosystem. How the interplay between tumor cells, EBV, and the microenvironment contributes to NPC progression and immune evasion remains unclear. Here we performed single-cell RNA sequencing on ~104,000 cells from 19 EBV(+) NPCs and 7 nonmalignant nasopharyngeal biopsies, simultaneously profiling the transcriptomes of malignant cells, EBV, stromal and immune cells. Overall, we identified global upregulation of interferon responses in the multicellular ecosystem of NPC. Notably, an epithelial–immune dual feature of malignant cells was discovered and associated with poor prognosis. Functional experiments revealed that tumor cells with this dual feature exhibited a higher capacity for tumorigenesis. Further characterization of the cellular components of the tumor microenvironment (TME) and their interactions with tumor cells revealed that the dual feature of tumor cells was positively correlated with the expression of co-inhibitory receptors on CD8(+) tumor-infiltrating T cells. In addition, tumor cells with the dual feature were found to repress IFN-γ production by T cells, demonstrating their capacity for immune suppression. Our results provide new insights into the multicellular ecosystem of NPC and offer important clinical implications.

Key Points Question What are the survival and toxicity outcomes associated with platinum plus low-dose, long-term fluorouracil compared with other chemotherapy regimens? Findings This cohort study of 1397 consecutive patients from 2006 to 2017 with metastatic nasopharyngeal carcinoma found that administration of platinum plus infusion of low-dose, long-term fluorouracil was associated with similar overall survival but better subsequent-line, treatment-free survival than other conventional chemotherapy regimens. Meaning Findings from this study suggest that platinum plus low-dose, long-term fluorouracil may be an optional treatment regimen to control disease progression for patients with metastatic nasopharyngeal carcinoma., Importance The treatment of metastatic nasopharyngeal carcinoma (mNPC) is a major challenge because of drug resistance and the toxic effects of chemotherapy. Objective To evaluate the survival and toxicity outcomes and safety associated with the use of a modified low-dose fluorouracil protocol compared with standard regimens recommended in current guidelines for treatment of mNPC. Design, Setting, and Participants This retrospective cohort study was based on data retrieved from electronic medical records from Sun Yat-sen University Cancer Center in China for 1397 patients with mNPC diagnosed from January 1, 2006, to December 31, 2017. Data analyses were conducted from October 1, 2020, to May 1, 2021. Exposures Patients received chemotherapy, including platinum plus low-dose, long-term fluorouracil (PFLL); cisplatin plus standard dose, short-term fluorouracil (PFSS); cisplatin plus gemcitabine (GP); cisplatin plus taxane (TP); and cisplatin plus taxane plus fluorouracil (TPF). Main Outcomes and Measures The main outcomes included overall survival (OS); subsequent-line, treatment-free survival (sTFS), defined as the period from metastasis to the date requiring subsequent-line treatment or death; and the survival to toxicity ratio (STR), defined as person-year rate of OS divided by person-year rate of severe hematologic toxic effects. Cox regression models were used to compare the outcomes of patients receiving PFLL vs other regimens, adjusting for baseline characteristics. Results Of 1397 patients with mNPC included in this study (1152 men; median age, 46 years [range, 18-70 years]) 134 received PFLL, 203 received GP, 330 received PFSS, 366 received TP, and 364 received TPF. A total of 764 patients died (75 in treatment group PFLL; 107 in group GP; 204 in group PFSS; 207 in group TP; and 171 in group TPF), and 979 patients had subsequent-line treatment or died, whichever occurred first (PFLL, 77; GP, 144; PFSS, 262; TP, 269; and TPF, 227). The median follow-up was 46.9 months (IQR, 25.4-82.4 months), and the 5-year OS rate among patients who received PFLL was 25.4% (95% CI, 16.7%-38.8%), which was not significantly different from that among patients who did not receive PFLL (30.2%; 95% CI, 27.1%-33.5%; P = .13) or who received GP (25.1%; 95% CI, 18.1%-35.0%; P = .81), PFSS (23.6%; 95% CI, 18.5%-30.0%; P = .80), or TP (28.1%; 95% CI, 22.8%-34.7%; P = .99) but was lower than that for patients who received TPF (40.4%; 95% CI, 34.7%-47.1%; P = .001). The 5-year sTFS among patients who received PFLL (24.1%; 95% CI, 15.4%-37.6%) was significantly higher than that among patients who did not receive PFLL (18.5%; 95% CI, 16.1%-21.3%; P = .005) or who received GP (14.3%; 95% CI, 9.1%-22.5%; P = .001) but similar to that for patients who received TPF (28.0%; 95% CI, 23.0%-34.0%; P = .74). The STR of PFLL was 0.81, substantially better than that of GP (0.41) and TPF (0.65). Conclusions and Relevance The results of this cohort study suggest that, compared with the use of standard treatment regimens, administration of PFLL was associated with similar OS but prolonged sTFS. PFLL also had better STR than other regimens, which could indicate less severe toxic effects. Thus, PFLL may be an option for first-line treatment of mNPC., This cohort study uses real-world evidence to assess the survival outcomes and hematologic toxic effects associated with the use of a low-dose, long-term infusion protocol for administration of fluorouracil vs standard regimens recommended in current guidelines for treatment of patients with metastatic nasopharyngeal carcinoma.

Natural killer/T-cell lymphoma (NKTCL) in children and adolescents is a rare type of T/NK cell neoplasms. The aim of the present study was to analyze the clinicopathological and genetic features of this rare entity of lymphoma. We evaluated the clinical, histopathological and molecular features of 22 young people with NKTCL, including 15 males and 7 females, with a median age of 15 years. The results revealed that the nasal site was the most involved region while non-nasal sites were observed in 27.3% out of all cases. The tumor cells were composed of small‑sized to large cells and 19 (86.4%) cases exhibited coagulative necrosis. The neoplastic cells in all patients were positive for CD3 and the cytotoxic markers. Nineteen (86.4%) cases were positive for CD56. Reduced expression of CD5 was observed in all available cases. CD30 was heterogeneously expressed in 15 (75.0%) cases. All 22 patients were EBV positive. Seven (36.8%) out of all the 19 patients during the follow-up died of the disease, and the median follow‑up period was 44 months. Moreover, patients treated with radiotherapy/chemotherapy showed significantly inferior OS compared with the untreated patients. High mutation frequencies were detected including KMT2C (5/5), MST1 (5/5), HLA-A (3/5) and BCL11A (3/5), which involved in modifications, tumor suppression and immune surveillance. These results suggest that NKTCL in children and adolescents exhibits histopathological and immunohistochemical features similar to the cases in adults. Active treatment is necessary after the diagnosis of NKTCL is confirmed. Furthermore, genetic analyse may provide a deep understanding of this rare disease.

This article studies the influence of physical interphase on magneto-electro-elastic (MEE) composites under far-field loading. The analytical solutions for the coupled transverse magnetoelectric field and axial displacement are given for fibrous composites with generalized plane strain assumption. The effect of interphase between fiber and matrix is considered through implementing the fiber-interphase and interphase-matrix continuities. Numerical results are used to verify that the axial stress, transverse electric and magnetic displacement distributions of composite materials with good agreement. The effect of interfacial thickness on the internal fields of fibrous composites is also investigated.

Purpose: To identify the association between ABO blood type and the survivals in nasopharyngeal carcinoma patients. Patients and methods: We retrospectively analyzed 2439 consecutive non-metastasis nasopharyngeal carcinoma patients between January 2001 and December 2004 at the Sun Yat-sen University Cancer Center. Survival outcomes were compared using Kaplan-Meier method. Univariate and multivariate analysis was performed by Cox regression model. Chi-square test was performed to compare categorical variables. Results: In the whole patients, compared with non-O blood type (A, B, and AB) patients, O blood type patients had significantly lower 5-year distant metastasis-free survival (DMFS) (adjusted hazard ratio (aHR)= 1.268, 95% CI 1.010-1.592, P=0.041). Moreover, we observed in female patients, O blood type patients had significantly lower 5-year overall survival (OS), disease-specific survival (DSS) and DMFS than those with non-O blood type (aHR=1.495, 95% CI 1.032-2.165, P=0.034 for OS; aHR=1.566, 95% CI 1.054-2.328, P=0.026 for DSS; aHR=1.779, 95% CI 1.056-2.998, P=0.030 for DMFS). In male patients, there was no significant difference observed between O blood type patients and non-O blood type patients in any survival endpoints. Conclusion: O blood type was associated with an unfavorable DMFS in female patients with nasopharyngeal carcinoma in epidemic area, which might contribute to unfavorable OS and DSS in female patients, even contribute to a lower DMFS in the whole patients. It might be beneficial to predict metastasis so as to guide the treatment in female patients with nasopharyngeal carcinoma in epidemic area.

Many porphyry and skarn Cu (Fe, Mo, Au, Zn) deposits have been discovered along the western Tianshan Orogenic Belt within the Central Asian Orogenic Belt. Generally, these Cu polymetallic deposits are considered to be linked to porphyries that formed in an arc setting, e.g., in a continental magmatic arc and island magmatic arc, but an agreement on their source region has not been reached. The Husite granitic complex and associated Kekesala skarn Fe-Cu deposit from the Boluokenu metallogenic belt provide significant insights into a comprehensive study of the ore-forming porphyries in Boluokenu. The ore-forming porphyries are mainly granodiorites and belong to calc-alkaline and high-K calc-alkaline series. LA-ICP-MS zircon U-Pb dating on the granodiorites yields ages of 368 Ma. The trace element compositions of the granodiorites are characterized by enrichment in large ion lithophile elements (LILE) and light rare earth elements (LREE), depletion in high field strength elements (HFSE) and heavy rare earth elements (HREE), and slightly negative Eu anomalies and are similar to rocks that form in a continental arc setting. These rocks also show large variations in their eHf (t) (+4.1 to +9.7) and Mg# (38–69) values, alongside low Ba/Th (4–230) and high Th/Yb (3.77–7.41) and Th/La (0.21–0.71) ratios, suggesting that the granodiorite magma originated from the partial melting of mafic lower crust with a mantle wedge component and involved signals of subduction-zone sediments and fluids. The Husite mafic microgranular enclaves (MMEs) exhibit high Mg# (50–62), MgO (3.25–6.93 wt%) and low SiO2 (48.8–59.5%) contents, with positive eHf(t) from +3.3 to +7.4. The zircon LA-ICP-MS U-Pb ages of the MMEs (373 Ma) indicate nearly coeval formation between the MMEs and HMPs during the Late Devonian. These features with the petrological and mineralogical characteristics (such as needle-like apatite and disequilibrium feldspar xenocrysts) suggest that the Husite MMEs formed from the mixing of felsic magma from the partial melting of mafic lower crust and mafic magma that was derived from mantle wedge, rather than restite, xenoliths or fractional crystallization of magma. Thus, the skarn Fe-Cu mineralization were probably related to hybrid intermediate-acid magma that is characterized by high water and oxygen contents and high sulfur fugacity. It can be inferred that the response to ongoing slab roll-back during the Junggar plate’s subduction beneath the Yili Block, including the underplating of mantle-derived mafic magmas from the metasomatism of subduction-zone melts, led to the partial melting of the mafic lower crust to form felsic magma. Then, the continuous reaction between the mafic and felsic magmas further increased the Fe-Cu concentrations and was closely related to the subsequent Fe-Cu mineralization.

BACKGROUND: The present study aimed to use magnetic resonance (MR) to explore the dynamic changes of the ischiofemoral space (IFS) under the triaxial motion of the hip joint and verify the clinical test mechanism for ischiofemoral impingement (IFI). METHODS: A prospective design was used to screen 37 patients with clinically confirmed IFI, which included a total of 67 lateral hips, and 39 healthy controls with a total of 69 lateral hips. A dynamic MR examination was performed in positions designed by a simulated IFI test (adduction, adduction with 30° external rotation, 30° internal rotation, supine with 30° flexion, and prone with 30° backward extension). The IFS (mm) and quadratus femoris space (QFS, mm) were measured in different positions. All the data were evaluated independently by three musculoskeletal radiologists. The differences between the two groups were compared using the two-tailed t-test. RESULTS: The IFS and QFS in the case group were smaller than those in the control group. The IFS and QFS were significantly reduced in the prone with backward extension and adduction with external rotation positions of the hip. The correlation coefficients of the IFI test and long-stride walking (LSW) test were –0.621 and –0.715 for IFS and –0.653 and –0.696 for QFS, respectively. CONCLUSIONS: In this study, the mechanism of the IFI-specific clinical examination (IFI and LSW tests) was verified by triaxial dynamic MR imaging of the hip joint, which provided a dynamic imaging basis for the clinical application of the IFI-specific impingement test. The IFI impingement test can be used as a specific clinical test for IFI screening.

To determine changes in clinical and radiologic findings associated with Coronavirus disease 2019 (COVID-19) from diagnosis to recovery, we retrospectively reviewed the diagnosis and treatment records of the first patient cured of COVID-19 in Guangzhou. A 55-year-old woman from Wuhan was admitted to the hospital isolation ward with the chief complaint of “cough for 11 days and once fever 8 days ago” on January 22, 2020. COVID-19 was laboratory confirmed by reverse transcription polymerase chain reaction (RT-PCR) assay, and she received conventional antiviral therapy, such as moxifloxacin, traditional Chinese medicine, and arbidol. Repeat chest-computed tomography (CT) scans were performed on days 13 and 19 of her illness. The former showed radiologic findings, including ground-glass opacities (GGOs), which revealed viral pneumonia; the latter revealed that the previous lesions had been significantly absorbed. The lesions on CT scans were consistent with the changes in the course of disease. Some drugs, such as traditional Chinese medicine and arbidol, might play an important role in the recovery of COVID-19 patients. This study provides some new insights into the formulation of a timely and effective diagnostic and therapeutic strategy to cure patients with COVID-19. Electronic supplementary material The online version of this article (10.1007/s42058-020-00045-z) contains supplementary material, which is available to authorized users.

The Boluokenu Range is one of the most important metallogenic belts in northwest China, and it contains numerous Fe, Cu, Mo, Au etc deposits. The Kendenggao’er Cu-Mo deposit is located in the eastern segment of the Boluokenu metallogenic belt within the Western Tianshan orogeny. Skarn and Cu-Mo orebodies occur as lamellae or lenses along the contacts between different units of the Upper Carboniferous Dongtujinhe Formation and the Aimujin granitic intrusions. Based on field investigations and petrographic observations, three main metallogenic stages of skarn formation and ore deposition have been distinguished: (1) The pre-ore stage is characterized by the formation of garnet, wollastonite and diopside and high-temperature, hypersaline hydrothermal fluids with oxygen isotopic compositions that are similar to those of magmatic fluids. These fluids were most likely generated by the separation of brine from the silicate melt due to the immiscibility of primary magmatic fluids that occurred at a depth of approximately 1 km with inferred lithostatic pressure conditions of 300 bars. (2) The main-ore stage coincides with the replacement of garnet and diopside by vesuvianite, epidote, sulfides and quartz. The hydrothermal fluids of this stage are represented by V-type (vapor-rich) fluid inclusions that coexist with L-type (liquid-rich) inclusions. The oxygen isotope (δ18OH2O) values of the main-ore stages are in a narrow range of 7.5–9.9‰, which indicates that the mineralization-related fluid is also of magmatic origin. Based on the fluid inclusion and stable isotopic data, it can be concluded that the ore-forming fluid evolved by the boiling of the magmatic fluids that likely occurred at a depth of ∼1 km and hydrostatic pressure of ∼100 bars, and that this was the predominant mechanism for the large-scale precipitation in the Kendenggao’er Cu-Mo deposit. (3) The post-ore stage is characterized by the development of calcite, quartz and chlorite. The fluids during this stage are represented by the L-type inclusions, which mainly show low-salinity and low-homogenization temperatures. These fluids yield the lowest δ18OH2O values (−2.8 to 3.7‰). The above data indicate that the post-ore stage fluids originated from the mixing of residual main-ore stage fluids with various proportions of external water (low salinity, low temperature). No boiling occurred at this stage at the low temperatures. The δ34S values of the sulfides range from −4.3 to 1.9‰, and the 206Pb/204Pb, 207Pb/204Pb and 208Pb/204Pb values of the sulfides range from 18.220 to 18.554, 15.608 to 15.812 and 38.080 to 39.055, respectively. The S and Pb isotopic compositions indicate that the ore materials were mainly derived from magmas. Taken together, these geologic, geochemical, and isotopic data confirm that Kendenggao’er is a typical skarn deposit.

The present study aimed to measure the expression of WNT1 in ameloblastoma (AB). Immunohistochemistry was used to observe changes in WNT1 expression in 80 AB samples, 10 keratocystic odontogenic tumor (KCOT) samples and 10 normal oral mucosa (NOM) samples. Western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to measure WNT1 protein and mRNA expression, respectively, in 30 AB samples, 5 KCOT samples, 5 NOM samples and 3 tooth germ samples. Ectopic cytoplasmic expression of WNT1 was detected in AB; 88.8% (71/80) of the samples were WNT1-positive. The western blotting results demonstrated that compared with NOM (0.57±0.05), WNT1 expression was significantly higher in AB tissue (1.74±0.36, P0.05). RT-qPCR revealed that the level of WNT1 gene expression in AB was increased 2.43-fold compared with normal mucosa, and 1.77-fold compared with tooth germ tissue. In conclusion, WNT1 protein and mRNA expression were increased in AB, and there was ectopic cytoplasmic expression. This indicates that WNT1 may serve an important role in AB occurrence and development.

Purpose: Investigating surrogate endpoints shortening the time of therapeutic evaluation in nasopharyngeal carcinoma (NPC) after radical treatment. Patients and Methods: We retrospectively analyzed 830 patients receiving intensity-modulated radiotherapy (IMRT) from 2008 to 2010 and being stratified by the 8th edition of UICC/AJCC staging system and the plasma Epstein-Barr virus DNA (EBV DNA). The annual rates of overall survival (OS), progression-free survival (PFS), loco-regional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were sequentially calculated using the life table and compared by the McNemar method. Results: The time of shortening therapeutic evaluation by surrogate endpoints: OS, PFS, LRFS and DMFS could be shortened to 1-year (100% vs 100%, P=1) in patients with stage I; OS, PFS, LRFS and DMFS could be shortened to 3-year (96.9% vs 96.1%, P = 1; 94.6% vs 92.2%, P = 0.125; 96.9% vs 95.3%, P = 0.5) and 4-year (92.2% vs 91.2%, P = 0.125) in stage II; In the high EBV DNA group , OS and DMFS could be shortened to 1-year (100% vs 100%, P = 1;100% vs 100%, P = 0.25) in stage II; OS and PFS could be shortened to 3-year (94.3% vs 91.4%, P = 1;82.9% vs 74.3%, P = 0.25) in stage III; OS could be shortened to 4-year (75% vs 72.7%, P = 1) in stage IVA. Conclusions: The time of therapeutic evaluation could be shortened to

Phenotypic flexibility in traits can allow organisms to cope with environmental challenges. However, the ecological consequences (e.g., growth) of SMR flexibility in fish are poorly understood. Juvenile qingbo (Spinibarbus sinensis) were reared individually with two levels of food resources (satiation or limited) with either continuous feeding (CF) or starvation-refeeding (SR). In the CF experiment, SMR increased when individuals were fed either the satiation or limited diets, but no difference was found in average specific growth rate somatic growth (SGR) between the two food availabilities. The relationship between flexibility in SMR and SGR, feeding efficiency (FE) and food intake (FI) was positive in the satiation group but not in the limited food group. In the SR experiment, the initial SMR of individuals was negatively correlated with the SGR during starvation. During refeeding, the starved individuals increased both body mass and SMR under both food availabilities. Individuals with a greater increase in SMR were fed more and also had greater SGR and FE under the satiation diet, but these results were not observed under the limited diet. The average FE under the limited diet was greater than that under the satiation diet, causing there to be no significant difference in final body mass between the diet treatments at the end of refeeding. Our study suggested that SMR flexibility can allow individuals to maximize their potential growth performance in an environment with changing food availability, and the benefits from greater flexibility in SMR could be offset by their maintenance metabolism under environmental stress.

Background Whether PD-L1/PD-1 expression plays a significant role in the prognosis of NPC is still controversial. The present study mainly aimed to investigate the prognostic significance of PD-L1/PD-1 expression in patients with NPC. Methods A systematical research was performed in the PubMed, Web of Science, EMBASE, and the Cochrane Library databases up to January 06, 2019. Eighteen studies met eligible criteria were included in the meta-analysis. Quality assessment of included articles was evaluated by Newcastle–Ottawa quality assessment scale (NOS). Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were used to elucidated the primary endpoint, overall survival (OS), and the secondary endpoints. Furthermore, the relationship between clinicopathological features of NPC and PD-L1/PD-1 expression was estimated by relative ratios (RRs) and 95% CIs. Results A total of 1836 patients from 15 included studies concerning PD-L1 and 678 patients from six studies regarding PD-1 were included in the meta-analysis. Pooled results revealed that PD-L1 expression in NPC did not correlate with OS (HR 1.34 95% CI 0.93–1.93, p = 0.11), DFS (HR 1.82, 95% CI 0.86–3.85, p = 0.12), PFS (HR 1.19, 95% CI 0.46–3.08, p = 0.72), and DMFS (HR 2.26, 95% CI 0.60–8.56, p = 0.23). Meanwhile, no statistically significant differences existed between the expression level of PD-1 in tumor infiltrating lymphocytes (TILs) and the OS in NPC, with the pooled HR 1.29 (95% CI 0.68–2.42, p = 0.44). In subgroup analysis, higher expression of PD-L1 in immune cells correlated with better OS in patients with NPC, with a pooled HR 0.68 (95% CI 0.47–0.99, p = 0.04). Among the clinicopathological features included in our study, we found that the positive expression of PD-L1 in NPC associated with the higher expression of PD-1 (RR 1.25, 95% CI 1.02–1.52, p = 0.03). Conclusions Our meta-analysis indicated that higher/positive expression of PD-L1/PD-1 may not serve as suitable biomarkers for the prognosis of NPC, which was not in consistent with some previous studies about the prognostic value of PD-L1/PD-1 in other types of tumors. Despite the positive results in subgroup analysis and study about clinicopathological features, it may still need corroboration of prospective and large-scale studies. Electronic supplementary material The online version of this article (10.1186/s12935-019-0863-5) contains supplementary material, which is available to authorized users.

Long noncoding RNAs (lncRNAs) have been implicated in colorectal cancer (CRC). And lncRNA RP11-138J23.1 (CRCAL-3) was previously reported as a candidate regulator of CRC development. But its regulating functions have not been fully elucidated. Here, we analyzed RNA sequencing data from the Cancer Genome Atlas (TCGA) and 253 CRC patients treated in our hospital to assess expression dysregulation of CRCAL-3, and the correlation between CRCAL-3 expression and disease progression. Further, polymerase chain reaction (PCR) assay on different cell lines and knockdown experiments by small interfering RNA were performed to assess functions of CRCAL-3 in proliferation and migration of CRC cells. As a result, analyses on TCGA datasets showed an upregulated CRCAL-3 expression in 14 solid tumors, including CRC. PCR assay on 253 cases of CRC tissue and 114 cases of normal adjacent tissue confirmed this expression upregulation. Also, CRCAL-3 expression was exhibited by survival analyses on the 253 CRC patients, to have a negative correlation with patients' overall and progression-free survivals. PCR assay on different cell lines showed that CRC cells expressed a higher level of CRCAL-3, compared with normal colonic epithelial cells. In vitro knockdown of CRCAL-3 resulted in an obvious retardation of proliferation and migration in two CRC cell lines (HCT116 and DLD-1). Moreover, CRCAL-3 knockdown was observed in xenograft models to repress cell proliferation and enhance cisplatin sensitivity. Taking these results together, CRCAL-3 emerged as a biomarker for early diagnosis, prognosis prediction, and individualized treatment of CRC.

It mainly solves the test lag, is not visual and the test efficiency is low, and relies on the test design of testers, and it cannot guarantee the quality of the test cases and cannot guarantee the quality of the test. According to the steps to establish the software data flow graph model to verify the model, the artificial point of the test items for planning. Finally fill in the contents of the test items and according to the algorithm to generate the corresponding test case collection, save to the database for management.

With the explosive growth of online news, adaptive news recommendation models based on social connections have developed as a result of the growth of online news websites. Several models have relayed better outcomes for users. Most of these models establish users' social connections according to their binary news rating scores. In various real systems, mainly based on a non-binary pattern, the rating score is often multigrade. In this paper, we introduce a new continuous ratings model for news recommendations. This model uses exponential distance to measure the similarities of users to increase its robustness to noise. Simulation results show that the proposed model has significantly improved the performance of personalized news recommendation.

Iminosugars have gained a remarkable importance as new therapeutic agents since 1966. In this study, compounds A and B, two iminosugar analogs synthesized previously, showed an inhibition of the growth of K562 cells. They allowed cell cycle arrested at the G0/G1 phase, promoted apoptotic activities and also lowered the mitochondrial membrane potential. Further exploration of the apoptosis mechanism revealed that compound B significantly suppressed the expression of Hsp70, which is a major anti-apoptotic molecular chaperone. Significant decrease was also found in the expression of Akt, a serine/threonine-specific protein kinase with anti-apoptosis activities also known as protein kinase B (PKB). At mitochondria level in comparison with compound A, compound B brought a better promotion in the expression of pro-apoptotic protein Bad in Bcl-2 family. As a result of the promotion, the expression of anti-apoptotic protein Bcl-xL was down-regulated. Cytochrome c was released, activating the intrinsic signaling pathways of caspase and resulting in the occurrence of cascade reaction. In addition, compound B stimulated autophagy effectively by up-regulating Beclin 1, thus causing the conversion of LC3-I to LC3-II through Akt/mTOR signaling pathway. In summary, these results indicated that compounds A and B induced cell death through multiple pathways. The disclosed results not only provide an evidence of antitumor activity of iminosugars as a foundation for further studies, but also may find potential applications in chronic myeloid leukemia therapy as new heat shock protein inhibitors and autophagy inducer.

Complementarity in lectin-glycan interactions in situ is assumed to involve spatial features in both the lectin and the glycan, giving a functional meaning to structural aspects of the lectin beyond its carbohydrate-binding site. In combining protein engineering with glycocluster synthesis, it is shown that the natural linker length of a tandem-repeat-type human lectin (galectin-4) determines binding properties in two binding assays (using surface-presented glycoprotein and cell surface assays). The types of glycocluster tested included bivalent lactosides based on tertiary amides of terephthalic, isophthalic, 2,6-naphthalic and oxalic acids as well as bivalent H(type 2) trisaccharides grafted on secondary/tertiary terephthalamides and two triazole-linker-containing cores. The presented data reveal a marked change in susceptibility to the test compounds when turning the tandem-repeat-type to a proto-type-like display. The testing of glycoclusters is suggested as a general strategy to help to delineate the significance of distinct structural features of lectins beyond their contact sites to the glycan. (C) 2014 Elsevier Ltd. All rights reserved. Science Foundation Ireland (08/SRC/B1393), the EC research/ITN programs GlycoHIT (contract no. 260600), COST (CM1102) and GLYCOPHARM (contract no. 217297) and the Verein zur Förderung des biologisch-technologischen Fortschritts in der Medizin e.V peer-reviewed 2016-05-07

Claspin is a critical mediator protein in the DNA replication checkpoint, responsible for ATR-dependent activation of the effector kinase Chk1. Cdc7, an essential kinase required for the initiation of DNA replication, can also interact with and phosphorylate Claspin. In this study we use small-molecule inhibitors of Cdc7 kinase to further understand the relationship between Cdc7, Claspin and Chk1 activation. We demonstrate that inhibition of Cdc7 kinase delays HU-induced phosphorylation of Chk1 but does not affect the maintenance of the replication checkpoint once it is established. We find that while chromatin association of Claspin is not affected by Cdc7 inhibition, Claspin phosphorylation is attenuated following HU treatment, which may be responsible for the altered kinetics of HU-induced Chk1 phosphorylation. We demonstrate that Claspin is an in vitro substrate of Cdc7 kinase, and using mass-spectrometry, we identify multiple phosphorylation sites that help to define a Cdc7 phosphorylation motif. Finally, we show that the interaction between Claspin and Cdc7 is not dependent on Cdc7 kinase activity, but Claspin interaction with the DNA helicase subunit Mcm2 is lost upon Cdc7 inhibition. We propose Cdc7-dependent phosphorylation regulates critical protein-protein interactions and modulates Claspin's function in the DNA replication checkpoint.

The glmS riboswitch is a ribozyme found in numerous Gram-positive bacteria and responds to the cellular concentrations of glucosamine 6-phosphate (GlcN6P). Given the importance of GlcN6P for cell wall biosynthesis, the glmS riboswitch has become a new drug target for the development of antibiotics. Herein, we describe the efficient synthesis of three GlcN6P analogues and their evaluation on inducing self-cleavage of the glmS riboswitch from Bacillus subtilis. Our results provide valuable information for further elucidation of the structure–activity relationships and drug design for glmS riboswitch antibiotics.

A series of N-substituted e-hexonolactams have been designed and prepared by a concise route with a tandem ring-expansion reaction as the key step. Some of the N-substituted e-hexonolactams show better enhancements to N370S mutant β-glucocerebrosidase activity than NB-DNJ and NN-DNJ. Both the experimental results and computational studies highlight the importance of the carbonyl group for stabilizing protein folds in the mutant enzyme. The structure–activity relationships are also discussed. These novel N-alkylated iminosugars are promising pharmacological chaperones for the treatment of N370S mutant Gaucher disease.

The relationship between alcohol drinking and the prognosis of nasopharyngeal carcinoma (NPC) is unknown. To investigate the prognostic value of alcohol drinking on NPC, this retrospective study was conducted on 1923 male NPC patients. Patients were classified as current, former and non-drinkers according to their drinking status. Furthermore, they were categorized as heavy drinkers and mild/none drinkers based on the intensity and duration of alcohol drinking. Survival outcomes were compared using Kaplan–Meier analysis and Cox proportional hazards model. We found that current drinkers had significantly lower overall survival (OS) rate (5-year OS: 70.2% vs. 76.4%, P P P = 0.022; HR = 1.38, 95% CI 1.09–1.75, P = 0.007). Stratified analyses further revealed that the negative impacts of alcohol were manifested mainly among older patients and among smokers. In conclusion, alcohol drinking is a useful predictor of prognosis in male NPC patients; drinkers, especially heavy drinkers have poorer prognosis.

A versatile and concise synthesis of N-alkylated 1,4-dideoxy-1,4-imino-D-arabinitol and 1,4-dideoxy-1,4-imino-L-xylitol derivatives is described. These were prepared using pseudohemiketal lactams as key intermediates, which in turn were obtained from sucrose. The key intermediates were prepared by a diastereospecific tandem reaction which facilitated the introduction of various substituents on the nitrogen atom of the iminosugars.

Highly potent N-substituted delta-lactams have been rationally designed and synthesized by a concise route with a one-pot tandem reaction as key step. These iminosugars show weak inhibition of wild-type beta-glucocerebrosidase but 3- to 6-fold increases in mutant enzyme activity (N370S).