Developmental stage related patterns of codon usage and genomic GC content: searching for evolutionary fingerprints with models of stem cell differentiation

Developmental-stage-related patterns of gene expression correlate with codon usage and genomic GC content in stem cell hierarchies

H-TSP: Hierarchically Solving the Large-Scale Travelling Salesman Problem

We propose an end-to-end learning framework based on hierarchical reinforcement learning, called H-TSP, for addressing the large-scale Travelling Salesman Problem (TSP). The proposed H-TSP constructs a solution of a TSP instance starting from the scratch relying on two components: the upper-level policy chooses a small subset of nodes (up to 200 in our experiment) from all nodes that are to be traversed, while the lower-level policy takes the chosen nodes as input and outputs a tour connecting them to the existing partial route (initially only containing the depot). After jointly training the upper-level and lower-level policies, our approach can directly generate solutions for the given TSP instances without relying on any time-consuming search procedures. To demonstrate effectiveness of the proposed approach, we have conducted extensive experiments on randomly generated TSP instances with different numbers of nodes. We show that H-TSP can achieve comparable results (gap 3.42% vs. 7.32%) as SOTA search-based approaches, and more importantly, we reduce the time consumption up to two orders of magnitude (3.32s vs. 395.85s). To the best of our knowledge, H-TSP is the first end-to-end deep reinforcement learning approach that can scale to TSP instances of up to 10000 nodes. Although there are still gaps to SOTA results with respect to solution quality, we believe that H-TSP will be useful for practical applications, particularly those that are time-sensitive e.g., on-call routing and ride hailing service.Comment: Accepted by AAAI 2023, February 202

PL - 034 Impact of PM2.5 Exposures and Pre-exercise on Pulmonary Function and Leukocyte Count in Aged Rats

Objective Exposure of PM2.5 has been associated with adverse respiratory and the risk of inflammation. While regular physical activity (PA) reduces the risk of many adverse health effects. This study aimed to examine the protection of pre-exercise on adverse health effects of Pulmonary Function and inflammatory induced by PM2.5 exposures in aged rats. Methods 24 male wistar rats, aged 16 months, were randomly divided into 4 groups: Sedentary (S), Exercise (E), Sedentary+ PM2.5 exposures (S+PM), and Exercise+ PM2.5 exposures (E+PM). The rats in all E-related groups went through an aerobic treadmill exercise protocol (15m/min, 30 min) at every other day. The PM-related groups of aged rats were exposed to concentrated ambient particles of less than 2.5 μm (PM2.5) or filtered air (FA) in Beijing, for 4 hours per day, 7 days per week for a total of 2 weeks. After 2-week PM Exposure, blood was taken to measure the count of white blood cell (WC), neutrophil (NE), lymphocytes (LY), monocyte (MO), eosinophils (EO) and basophil (BA), and pulmonary function examined by whole body plethysmography. Results After 2-week PM exposure, compared with E group, S+PM group’ s percentage of NE decreased significantly (p＜0.05), while the decline of NE% in E+PM group was small. Meanwhile, the obviously rise of BA% occurred in S+PM and E+PM group compared with sedentary group (p＜0.05). 2) Compared with E group, the Index of constriction (Penh and PAU) were increased evidently in S+PM group after PM exposure (p＜0.05), while the value of Penh were significantly improved in E+PM group (p＜0.05). 3) Compared with E group, the rejection index (RinX) (p＜0.01) and duration of pause before inspiration (TP) (p＜0.05) were appeared a clearly inclined in S+PM group, as well as several up-regulated of RinX and TP showed in E+PM group. Conclusions 2-week PM2.5 exposures led to an increased susceptibility of infections, index of constriction and susceptibility of pulmonary function in aged rats. Moderate pre-exercise has beneficial effects on pulmonary function and immune function

Derivation and Characterization of Hepatic Progenitor Cells from Human Embryonic Stem Cells

The derivation of hepatic progenitor cells from human embryonic stem (hES) cells is of value both in the study of early human liver organogenesis and in the creation of an unlimited source of donor cells for hepatocyte transplantation therapy. Here, we report for the first time the generation of hepatic progenitor cells derived from hES cells. Hepatic endoderm cells were generated by activating FGF and BMP pathways and were then purified by fluorescence activated cell sorting using a newly identified surface marker, N-cadherin. After co-culture with STO feeder cells, these purified hepatic endoderm cells yielded hepatic progenitor colonies, which possessed the proliferation potential to be cultured for an extended period of more than 100 days. With extensive expansion, they co-expressed the hepatic marker AFP and the biliary lineage marker KRT7 and maintained bipotential differentiation capacity. They were able to differentiate into hepatocyte-like cells, which expressed ALB and AAT, and into cholangiocyte-like cells, which formed duct-like cyst structures, expressed KRT19 and KRT7, and acquired epithelial polarity. In conclusion, this is the first report of the generation of proliferative and bipotential hepatic progenitor cells from hES cells. These hES cell–derived hepatic progenitor cells could be effectively used as an in vitro model for studying the mechanisms of hepatic stem/progenitor cell origin, self-renewal and differentiation

PO-181 The Comparative Study on the Maximum Oxygen Uptake Test of 10- Month Old Wistar Rats: There is no full text article associated with this abstract

Objective The maximum oxygen uptake (VO2max) is an ideal index to objectively evaluate the cardiopulmonary function, as well as the basic to define exercise intensity. In the field of sports science, laboratory animals are often used to explore the effect and mechanism of exercise intervention. Therefore, it is very important to design optimal VO2max test protocol and to ensure the accuracy of VO2max according to the characteristics of the experimental animal itself. In this study, Wistar rats were selected, and various VO2max test protocols were designed and analyzed to screen out the optimal VO2max test protocol for the 10-month old wistar rats. Methods  20 SPF Wistar rats (male, 10 month old) were tested for maximal oxygen uptake by a four channel metabolic monitoring system and running treadmill. Five different test protocols were executed. Each rat completed five test protocols in random order with 3 days’ interval. The exercise performance (coordination degree, exhaustion state), oxygen uptake platform, finish time, VO2max and RER value were recorded during the test of each program, and the performance and test data were compared. Results  1) 12 rats completed all 5 test protocols of VO2max. The induction ratio of VO2max of P1 was only 58%, and P2 and P4 were 75%. While, the induction rate of P3 and P5 were both 83%. 2) For the Bedford improvement protocol (P1), due to the intense increased exercise load, the rats showed more intense stress, the less coordination degree, injured even death, and lower induction rate of VO2max. 3) The VO2max and RER values induced by the P5 are significantly higher than that of P1 (p<0.05). The finish time of P3 is significantly higher than that of P1 (p<0.01) and P5 (p<0.05). Conclusions For the VO2max test for middle aged rats, with the suitable speed of the running treadmill, the change of gradient should be as the main way of increasing load, or increasing the gradient of the slope firstly, which can obtained optimal VO2max, meanwhile reduce the stress response and the risk of injury and serious damage

Acupuncture for chronic, stable angina pectoris and an investigation of the characteristics of acupoint specificity: study protocol for a multicenter randomized controlled trial

BACKGROUND: Chronic stable angina pectoris (CSAP) is a common cardiovascular condition that endangers a patient’s life quality and longevity. As demonstrated in several clinical trials, acupuncture is attested to be effective for CSAP. Current trials are not adequate enough to provide high-quality evidence for clinical decision making, as a result of inadequate methodology design and small sample size. Notably, stark controversy toward acupoint specificity also exists in the clinical acupuncture trials for CSAP. Therefore, we designed the present study as a randomized controlled trial primarily to investigate the effectiveness of acupuncture in addition to routine care among patients with CSAP. Meanwhile, we examined whether acupoint on the disease-affected meridian (DAM) is superior to either acupoint on the non-affected meridian (NAM) or non-acupoint (NA), to further investigate the meridian-based characteristics of acupoint specificity. METHODS/DESIGN: This study was a multicenter, assessor and statistician blinded, randomized controlled trial in China. In this study, 404 participants in sum will be randomly assigned to four groups through central randomization in a 1:1:1:1 ratio. The whole study period is 20 weeks including a 4-week baseline period, a 4-week treatment period and a 12-week follow-up. Participants in the DAM group receive acupuncture stimulation at acupoints on the disease-affected meridian, and three different control groups will undergo acupuncture stimulation at the NAM, the non-acupoint and no intervention respectively, in addition to basic treatment. Participants in the acupuncture groups will receive 12 sessions of acupuncture treatment over 4 weeks, while the wait-listed (WL) group would receive free acupuncture treatment after the completion of the study. The outcome measures in this trial include the frequency of angina attack during 4 weeks as the primary outcome and eight other secondary outcomes. DISCUSSION: This trial will provide new and relatively high-quality evidence in acupuncture treatment for CSAP. Moreover, this trial may further validate the meridian-based characteristics of acupoint specificity by comparing the strength of acupoints on the disease-affected meridian versus that of the non-affected meridian, to further inspire optimization of acupuncture therapy for CSAP. TRIAL REGISTRATION: Clinical Trials.gov NCT0168623

Undergraduates' perceptions on emergency remote learning in ecology in the post‐pandemic era

The COVID-19 pandemic has strongly disrupted academic activities, particularly in disciplines with a strong empirical component among other reasons by limiting our mobility. It is thus essential to assess emergency remote teaching plans by surveying learners’ opinions and perceptions during these unusual circumstances. To achieve this aim, we conducted a survey during the spring semester of 2021 in an environmental science program to ascertain learners’ perceptions on online and onsite learning activities in ecology-based modules. We were particularly interested not only in comparing the performance of these two types of activities but also in understanding the role played by learners’ perceptions about nature in shaping this pattern. Environmental science programs are rather heterogeneous from a conceptual point of view and, thus, learners may also be more diverse than in traditional ecology programs, which may affect their interest for ecology-based modules. We assessed connectedness to nature by computing the reduced version of the Nature Relatedness Scale. Here, we found that online activities systematically obtained significantly lower scores than onsite activities regardless of the wording employed, and that altruistic behaviors were prevalent among learners. Interestingly, scores for both onsite and online activities were strongly influenced by learners’ connectedness to nature, as learners with a stronger connection to nature gave higher scores to both types of activities. Our results suggest that an effort to improve the efficacy of remote learning activities should be the focus of research about teaching methodologies in predominantly empirical scientific disciplines

Safety and efficacy of lentinan nasal drops in patients infected with the variant of COVID-19: a randomized, placebo-controlled trial

Objective: Lentinan has antiviral, anti-tumor, immunomodulatory, stimulating interferon production, and other pharmacological effects. Previous animal experiments have shown that lentinan nasal drops can assist [Corona Virus Disease 2019) COVID-19] vaccine to induce high levels of neutralizing antibodies and can effectively resist the invasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the safety and efficacy of lentinan nasal drops in patients infected with Omicron (SARS-CoV-2 variant) through a dose-escalation study and a placebo-controlled trial.Methods: A randomized, placebo-controlled trial. The study was divided into two phases: Phase I: a dose escalation trial in which 24 COVID-19 patients were enrolled, that is, 12 in the escalation dose group (50, 75, and 100 µg/day) and 12 in the standard treatment group. The aim was to evaluate the safety and tolerance of lentinan nasal drops. The second stage was a placebo-controlled study. The optimal dose group of the first stage was used as the therapeutic dose, and the sample size was expanded to verify the anti-COVID-19 efficacy of lentinan nasal drops.Results: In the dose-increasing study, lentinan nasal drops showed good safety, and no serious adverse reactions occurred. The virus shedding time of the 100 µg dose group was significantly shorter than that in the control group (7.75 ± 1.71 VS 13.41 ± 3.8 days) (p = 0.01), and the 100 µg/day lentinan nasal drops were tolerated well. The results of the placebo-controlled study showed that compared with that in the placebo group, the time for COVID-19 antigen to turn negative was significantly shorter in the 100 µg lentinan nasal drop group (p = 0.0298), but no significant difference was observed in symptom improvement between the two groups. In the placebo-controlled study, two patients experienced mild nasal discomfort with nasal drops, but the symptoms relieved themselves.Conclusion: Lentinan nasal drops are tolerated well and can shorten the time of virus clearance

A prognostic estimation model based on mRNA-sequence data for patients with oligodendroglioma

BackgroundThe diagnosis of oligodendroglioma based on the latest World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS 5) criteria requires the codeletion of chromosome arms 1p and 19q and isocitrate dehydrogenase gene (IDH) mutation (mut). Previously identified prognostic indicators may not be completely suitable for patients with oligodendroglioma based on the new diagnostic criteria. To find potential prognostic indicators for oligodendroglioma, we analyzed the expression of mRNAs of oligodendrogliomas in Chinese Glioma Genome Atlas (CGGA).MethodsWe collected 165 CGGA oligodendroglioma mRNA-sequence datasets and divided them into two cohorts. Patients in the two cohorts were further classified into long-survival and short-survival subgroups. The most predictive mRNAs were filtered out of differentially expressed mRNAs (DE mRNAs) between long-survival and short-survival patients in the training cohort by least absolute shrinkage and selection operator (LASSO), and risk scores of patients were calculated. Univariate and multivariate analyses were performed to screen factors associated with survival and establish the prognostic model. qRT-PCR was used to validate the expression differences of mRNAs.ResultsA total of 88 DE mRNAs were identified between the long-survival and the short-survival groups in the training cohort. Seven RNAs were selected to calculate risk scores. Univariate analysis showed that risk level, age, and primary-or-recurrent status (PRS) type were statistically correlated with survival and were used as factors to establish a prognostic model for patients with oligodendroglioma. The model showed an optimal predictive accuracy with a C-index of 0.912 (95% CI, 0.679–0.981) and harbored a good agreement between the predictions and observations in both training and validation cohorts.ConclusionWe established a prognostic model based on mRNA-sequence data for patients with oligodendroglioma. The predictive ability of this model was validated in a validation cohort, which demonstrated optimal accuracy. The 7 mRNAs included in the model would help predict the prognosis of patients and guide personalized treatment