Comparative Analysis of Water-Soluble Polysaccharides from <i>Dendrobium</i> Second Love ‘Tokimeki’ and <i>Dendrobium nobile</i> in Structure, Antioxidant, and Anti-Tumor Activity In Vitro

With potential anti-tumor and antioxidant properties, the polysaccharide content of D. nobile is relatively lower than that of the other medicinal Dendrobium. To find high-content polysaccharide resources, the polysaccharide (DHPP-Ⅰs) was prepared from D. Second Love ‘Tokimeki’ (a D. nobile hybrid) and compared with DNPP-Ⅰs from D. nobile. DHPP-Is (Mn 31.09 kDa) and DNPP-Is (Mn 46.65 kDa) were found to be O-acetylated glucomannans (-Glcp-(1,4) and O-acetylated-D-Manp-(1,4) backbones), analogous to other Dendrobium polysaccharides. DHPP-Ⅰs had higher glucose content (31.1%) and a lower degree (0.16) of acetylation than DNPP-Ⅰs (15.8%, 0.28). Meanwhile, DHPP-Ⅰs and DNPP-Ⅰs had the same ability in the radical scavenging assay, which was milder than the control of Vc. Both DHPP-Is and DNPP-Is inhibited SPC-A-1 cell proliferation in vitro, with obvious differences in dose concentrations (0.5–2.0 mg/mL) and treatment times (24–72 h). Therefore, the antioxidant activity of DHPP-Ⅰs and DNPP-Ⅰs is not associated with distinction in anti-proliferative activity. As a glucomannan derived from non-medicinal Dendrobium, DHPP-Ⅰs has similar bioactivity to other medicinal Dendrobium, and this could serve as a starting point for studying the conformational–bioactivity relationship of Dendrobium polysaccharides

Integrating sugarcane molasses into sequential cellulosic biofuel production based on SSF process of high solid loading

Abstract Background Sugarcane bagasse (SCB) is one of the most promising lignocellulosic biomasses for use in the production of biofuels. However, bioethanol production from pure SCB fermentation is still limited by its high process cost and low fermentation efficiency. Sugarcane molasses, as a carbohydrate-rich biomass, can provide fermentable sugars for ethanol production. Herein, to reduce high processing costs, molasses was integrated into lignocellulosic ethanol production in batch modes to improve the fermentation system and to boost the final ethanol concentration and yield. Results The co-fermentation of pretreated SCB and molasses at ratios of 3:1 (mixture A) and 1:1 (mixture B) were conducted at solid loadings of 12% to 32%, and the fermentation of pretreated SCB alone at the same solid loading was also compared. At a solid loading of 32%, the ethanol concentrations of 64.10 g/L, 74.69 g/L, and 75.64 g/L were obtained from pure SCB, mixture A, and mixture B, respectively. To further boost the ethanol concentration, the fermentation of mixture B (1:1), with higher solid loading from 36 to 48%, was also implemented. The highest ethanol concentration of 94.20 g/L was generated at a high solid loading of 44%, with an ethanol yield of 72.37%. In addition, after evaporation, the wastewater could be converted to biogas by anaerobic digestion. The final methane production of 312.14 mL/g volatile solids (VS) was obtained, and the final chemical oxygen demand removal and VS degradation efficiency was 85.9% and 95.9%, respectively. Conclusions Molasses could provide a good environment for the growth of yeast and inoculum. Integrating sugarcane molasses into sequential cellulosic biofuel production could improve the utilization of biomass resources

Assessing Distinct Cognitive Workload Levels Associated with Unambiguous and Ambiguous Pronoun Resolutions in Human–Machine Interactions

Pronoun resolution plays an important role in language comprehension. However, little is known about its recruited cognitive mechanisms. Our investigation aims to explore the cognitive mechanisms underlying various types of pronoun resolution in Chinese using an electroencephalograph (EEG). We used three convolutional neural networks (CNNs)—LeNeT-5, GoogleNet, and EffifcientNet—to discover high-level feature abstractions of the EEG spatial topologies. The output of the three models was then fused using different scales by principal component analysis (PCA) to achieve cognitive workload classification. Overall, the workload classification rate by fusing three deep networks can be achieved at 55–63% in a participant-specific manner. We provide evidence that both the behavioral indicator of reaction time and the neural indicator of cognitive workload collected during pronoun resolution vary depending on the type of the pronoun. We observed an increase in reaction time accompanied by a decrease of the theta power while participants were processing ambiguous pronoun resolution compared to unambiguous controls. We propose that ambiguous pronoun resolution involves a more time-consuming yet more flexible cognitive mechanism, consistent with the predictions of the decision-making framework from an influential pragmatic tradition. Our results extend previous research that the cognitive states of resolving ambiguous and unambiguous pronouns are differentiated, indicating that cognitive workload evaluated using the method of machine learning for analysis of EEG signals acts as a complementary indicator for studying pronoun resolution and serves as an important inspiration for human–machine interaction

The effect of methamphetamine abuse on dental caries and periodontal diseases in an Eastern China city

Abstract Background Dental diseases are among the most frequently reported health problems in drug abusers. However, few studies have been conducted on oral health of methamphetamine (meth) abusers in China. The aim of the present study was to investigate the caries and periodontal health profile of former meth abusers in Eastern China. Methods A cross-sectional study was conducted on 162 former meth abusers in the male Zhoushan Compulsory Detoxification Center. A standardized questionnaire, which collected information about age, drug-use duration / pattern, oral hygiene habit and systemic diseases, was administered. Then, a dental examination was performed to investigate the severity of dental caries and periodontal diseases. In evaluating dental caries, the prevalence of dental caries, the scores of decayed teeth (DT), missing teeth (MT), filled teeth (FT), and decayed, missing, filled teeth (DMFT) were recorded. In evaluating periodontal diseases, community periodontal index (CPI), and the prevalence of gingival bleeding, dental calculus, periodontal pocket and loose teeth, were recorded. Additionally, the non-parametric test was adopted to analyze the potential risk factors via SPSS. Results All the participants abused meth by inhalation. The mean scores of DT, MT, FT and DMFT in the former meth users were 2.72 ± 2.78, 3.07 ± 3.94, 0.33 ± 1.03 and 6.13 ± 5.20 respectively. The prevalence of gingival bleeding, dental calculus, periodontal pocket and loose teeth was 97.53%, 95.68%, 51.23% and 9.26% respectively. The DT, DMFT and CPI scores in those who had abused meth for longer than 4 years were significantly higher than those who abused for less than 4 years (P = 0.039, 0.045, P < 0.001, respectively). The DT score in those who brushed their teeth more than twice a day were significantly lower than those who brushed less (P = 0.018). Conclusions The status of caries and periodontal diseases among former male meth users in Eastern China was poor. Prolonged drug abuse and lower frequency of tooth brushing may be the risk factors of their poor status of caries and periodontal diseases

A Phase I/II Study of Chemotherapy Concurrent with Twice-daily Radiotherapy Schedules by Intensity Modulated Radiation Therapy Using Simultaneous Integrated Boost for Limited-stage Small Cell Lung Cancer

Background and objective Twice-daily radiation concurrent with chemotherapy is one of the standard methods for limited-stage small cell lung cancer. The study was to evaluate the feasibility of chemotherapy concurrent with dose-escalating twice-daily radiotherapy by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) approach in patients with limited-stage small cell lung cancer. Methods Patients with limited-stage small cell lung cancer were included, treated with twice-daily radiotherapy by SIB-IMRT concurrent with chemotherapy of etoposide plus cisplatin. Dose escalation was conducted by “classical” 3+3 methods with three patients enrolled in each dose level. The therapeutic gross tumor volume (GTV) was treated according to three consecutive dose levels i.e., 45 Gy at 1.5 Gy twice daily, 50 Gy at 1.67 Gy twice daily and 54 Gy at 1.8 Gy twice daily. The planning target volume (PTV) received a dose of 45 Gy delivered in 30 fractions of 1.5 Gy. The primary endpoints were acute toxicities. The secondary endpoints included overall survival (OS), progression-free survival (PFS) and loco-regional failure-free survival (LRFFS) at 1-year of follow-up. Results Twenty men and six women were included. The median age was 52 (30-68) months. 12 patients experienced grade 2 acute esophagitis, and 1 patient developed grade 3 acute esophagitis. Only 3 patients developed Grade 2 pneumonitis. Grade 3 or higher radiation-related pneumonia was not observed. None died of treatment-related causes. With median follow-up of 11.2 months (3.2-36.2 months), 1-year OS, PFS and LRFFS were 89.0%, 51.0% and 85.0%, respectively. Conclusion Dose escalation for twice-daily radiation concurrent with chemotherapy in LS-SCLC has been safely achieved up to 54 Gy for GTV using SIB-IMRT technique

Phase I Study of Etoposide and Cisplatin Chemotherapy Dose Escalation with Concurrent Twice-daily Radiotherapy for Patients with Limited-stage Small Cell Lung Cancer

Background and objective Concurrent twice-daily radiotherapy with chemotherapy of EP regimen is one of the current standard treatments for limited-stage small cell lung cancer. However, the safely tolerated dose of standard chemotherapy for Chinese patients is not decided. This study was to evaluate the toxicity and the maximum tolerated dose (MTD) of etoposide and cisplatin concurrent with thoracic radiation therapy for patients with limited-stage small cell lung cancer. Methods Patients with histologically proven limited-stage small cell lung cancer (LS-SCLC) were eligible. The patients underwent thoracic radiotherapy (45 Gy, 1.5 Gy bid, 30 fractions for 3 weeks) delivered concurrently with etoposide (100 mg/m2 iv, days 1-3) and cisplatin dose escalating from the two levels ( 70 mg/m2 and 75 mg/m2 on d1). The primary endpoints were hematologic toxicities during treatment. The secondary endpoints were non-hematologic toxicities, overall survival (OS) and progression-free survival (PFS). According to Common Terminology Criteria for Adverse Events 4.0 (CTC-AE 4.0), maximum tolerant dosage (MTD) was defined as the highest safely tolerated dose at which no more than one patient out of six experiences dose-limiting toxicity (Grades 4 hematologic), with the next higher dose having at least two out of six patients experience dose-limiting toxicity. Results From January 2013 to August 2016, 20 patients were enrolled in this study. The median age was 49.5 (30-68). After the first 6 patients were enrolled in Arm 1 (70 mg/m2 on d1), one patient had Grade 4 neutropenia. Another 14 patients were enrolled in Arm 2 (75 mg/m2 on d1), one patient had Grade 4 neutropenia. The MTD was determined to be etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1). 4 patients had ≥Grade 3 neutropenia and 1 patients had ≥Grade 3 acute esophagitis in Arm 1. 10 patients had ≥Grade 3 neutropenia and no patient had ≥Grade 3 acute esophagitis in Arm 2. All patients with a median follow-up time was 9.0 months, median OS and PFS were not achieved, 1-year OS and PFS were 91% and 61%, respectively. Conclusion The MTD of RT with concurrent chemotherapy of EP regimen for patients with LS-SCLC was etoposide (100 mg/m2 iv, d1-d3) and cisplatin dose (75 mg/m2 on d1)

PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, produces an antitumor effect in B16-F10 melanoma-bearing mice.

The increased PD-L1 expression induces poorer prognosis in melanoma. The small molecule inhibitors of PD-1/PD-L1 pathways have been an encouraging drug development strategy because of good affinity and oral bioavailability without immunogenicity and immunotoxicities of PD-1/PD-L1 antibodies. In this study, we studied the effects of PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, on PD-1/PD-L1 binding and the cytokines secretion in human CD3+ cells in vitro. We also investigated the antitumor and immunomodulatory activity of PCC0208025 and the pharmacokinetics properties in B16-F10 melanoma-bearing mice. The results showed that PCC0208025 inhibited the PD-1/PD-L1 proteins binding, and rescued PD-L1-mediated inhibition of IFN-γ production in human CD3+ T cells in vitro. Furthermore, in B16-F10 melanoma-bearing mice, PCC0208025 presented the antitumor effects, enhanced IFN-γ levels in plasma, increased the frequency of CD3+CD8+ T and CD8+IFN-γ+ T and the ratios of CD8+/Treg, and deceased the CD4+CD25+CD127low/- (Treg) number in tumor. Pharmacokinetics study found that PCC0208025 was absorbed and distributed into the tumors with much higher concentrations than those of the blockade against PD-1/PD-L1 binding. Our work suggests that PCC0208025 exhibited anti-tumor effects through inhibiting Treg expansion and increasing cytotoxic activity of tumor-infiltrating CD8+ T cells by the blockade of PD-1/PD-L1 binding, which may provide the pharmacological basis to develop small molecule inhibitors of PD-1/PD-L1 binding for PCC0208025 as a lead compound