MindDial: Belief Dynamics Tracking with Theory-of-Mind Modeling for Situated Neural Dialogue Generation

Humans talk in free-form while negotiating the expressed meanings or common ground. Despite the impressive conversational abilities of the large generative language models, they do not consider the individual differences in contextual understanding in a shared situated environment. In this work, we propose MindDial, a novel conversational framework that can generate situated free-form responses to negotiate common ground. We design an explicit mind module that can track three-level beliefs -- the speaker's belief, the speaker's prediction of the listener's belief, and the common belief based on the gap between the first two. Then the speaking act classification head will decide to continue to talk, end this turn, or take task-related action. We augment a common ground alignment dataset MutualFriend with belief dynamics annotation, of which the goal is to find a single mutual friend based on the free chat between two agents. Experiments show that our model with mental state modeling can resemble human responses when aligning common ground meanwhile mimic the natural human conversation flow. The ablation study further validates the third-level common belief can aggregate information of the first and second-order beliefs and align common ground more efficiently

Identification of random amplified polymorphic DNA (RAPD) marker of Ph-3 gene for late blight resistance in tomato

Late blight is a highly destructive disease of tomato worldwide. Host resistance is the most effective method for disease control. The application of molecular markers is an efficient way to identify host resistance for breeding programs. In this study, bulked segregant analysis (BSA) was used to search for random amplified polymorphic DNA (RAPD) markers linked to the late blight resistance gene Ph-3, using an F2 population (147 individuals) derived from a cross of tomato lines CLN2037 (resistant) and T2-03 (susceptible). Two hundred and thirty decamer primers with arbitrary sequences were chosen for polymerase chain reaction amplification. One RAPD marker CCPB272-03740 (primer sequence GGTCGATCTG) was found to be tightly linked to the resistance gene Ph-3 and was located 5.8 cm from the resistance gene. Marker CCPB272-03740 is the first marker of gene Ph-3 based on PCR reaction.Key words: Tomato, late blight, random amplified polymorphic DNA (RAPD) marker, gene Ph-3

Clinical Characteristics and Short-Term Prognosis of Autoimmune Encephalitis: A Single-Center Cohort Study in Changsha, China

Background and Purpose: The incidence and prevalence of autoimmune encephalitis is gradually increasing. This retrospective observational study primarily aimed to analyze the clinical characteristics of autoimmune encephalitis patients in the Second Xiangya Hospital and report patient prognoses after immunotherapy.Methods: The clinical data of 86 patients who were diagnosed with autoimmune encephalitis from October 2014 to September 2018 were collected, and their corresponding clinical characteristics, laboratory examination, treatment, and outcome data analyzed.Results: In our study, 72 patients (83.7%) were positive for anti-NMDAR (N-methyl-D-aspartate receptor) antibody; 5 patients (6%) for anti-GABABR (γ-aminobutyric acid receptor-A); 4 patients (4.7%) for anti-LGI1 (leucine-rich, glioma inactivated 1); 3 patients (3.5%) for anti-Caspr2 (contactin-associated protein-like 2) (1 patient was positive for both anti-LGI1 and anti-Caspr2 antibodies); and 3 patients (3.5%) for onconeural antibodies. Among the 86 patients diagnosed as having autoimmune encephalitis, 50% showed acute disease onset (≤2 weeks). The most common inducing factor was fever or cold (17/86, 19.8%). The main clinical symptoms included, among others, psychiatric disturbances (82.5%), epilepsy (60.5%), autonomic dysfunction (58.1%), sleep disorders (45.3%), consciousness disorders (45.3%), and speech disorders (46.5%). No significant correlation between ICU admission rates and CSF or serum antibody scores was observed. However, CSF antibody scores of (+ + +) and (++) were associated with longer lengths of hospitalization (p < 0.05) and a higher CSF WBC count when compared with CSF antibody scores of (+) in patients with anti-NMDAR encephalitis (p < 0.05). Additionally, there was no significant correlation between mRS score difference on admission and discharge (after immunotherapy) and age, sex, and choice of immune treatment, while immune therapy taken within 15 days from onset was more inclined to be associated with an mRS score difference ≥2 after immunotherapy in patients with anti-NMDAR encephalitis (p = 0.006).Conclusions: Autoimmune encephalitis has an acute or sub-acute onset and presents with psychotic symptoms, epilepsy, and autonomic dysfunction. The sex ratio in anti-NMDAR encephalitis was nearly balanced. Infection was a major factor inducing anti-NMDAR encephalitis, and the CSF antibody scores could be helpful in determining its prognosis since these scores showed associations with hospitalization duration and CSF WBC counts

Synthesis and Biological Activities of a 3′-Azido Analogue of Doxorubicin Against Drug-Resistant Cancer Cells

Doxorubicin (DOX), an anthracycline antibiotic, is one of the most active anticancer chemotherapeutic agents. The clinical use of DOX, however, is limited by the dose-dependant P-glycoprotein (P-gp)-mediated resistance. Herein, a 3′-azido analogue of DOX (ADOX) was prepared from daunorubicin (DNR). ADOX exhibited potent antitumor activities in drug-sensitive (MCF-7 and K562) and drug-resistant cell lines (MCF-7/DNR, K562/DOX), respectively. The drug resistance index (DRI) values of ADOX were much lower than that of DOX. The cytotoxicity experiments of ADOX or DOX against K562/DOX, with or without P-gp inhibitor, indicated that ADOX circumvents resistance by abolishing the P-gp recognition. This conclusion was further supported by drug influx/efflux flow cytometry experiments, as well as by molecular docking of ADOX to P-gp. In vivo animal tests, ADOX exhibited higher activity and less toxicity than DOX. The current data warranted ADOX for additional pre-clinical evaluations for new drug development

Interleukin-17 Contributes to the Pathogenesis of Autoimmune Hepatitis through Inducing Hepatic Interleukin-6 Expression

T helper cells that produce IL-17 (Th17 cells) have recently been identified as the third distinct subset of effector T cells. Emerging data suggests that Th17 cells play an important role in the pathogenesis of many liver diseases by regulating innate immunity, adaptive immunity, and autoimmunity. In this study, we examine the role and mechanism of Th17 cells in the pathogenesis of autoimmune hepatitis (AIH). The serum levels of IL-17 and IL-23, as well as the frequency of IL-17+ cells in the liver, were significantly elevated in patients with AIH, compared to other chronic hepatitis and healthy controls. The hepatic expressions of IL-17, IL-23, ROR-γt, IL-6 and IL-1β in patients with AIH were also significantly increased and were associated with increased inflammation and fibrosis. IL-17 induces IL-6 expression via the MAPK signaling pathway in hepatocytes, which, in turn, may further stimulate Th17 cells and forms a positive feedback loop. In conclusion, Th17 cells are key effector T cells that regulate the pathogenesis of AIH, via induction of MAPK dependent hepatic IL-6 expression. Blocking the signaling pathway and interrupting the positive feedback loop are potential therapeutic targets for autoimmune hepatitis

Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study

IntroductionObservational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation.MethodsFor Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments.ResultsOur results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34–4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32–3.43]), benign neoplasm of the larynx (2.01 [1.36–2.96]), melanoma (1.74 [1.17–2.59]), follicular lymphoma (1.50 [1.06–2.11]), autoimmune thyroiditis (2.47 [1.49–4.08]), and autoimmune hyperthyroidism (1.93 [1.17–3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland.ConclusionCasting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported

“Smart ” Materials Based on Cellulose: A Review of the Preparations, Properties, and Applications

material

Enhancement of the Controlled-Release Properties of Chitosan Membranes by Crosslinking with Suberoyl Chloride

A novel crosslinking agent, suberoyl chloride, was used to crosslink N-phthaloyl acylated chitosan and improves the properties of chitosan membranes. Membranes with different crosslinking degrees were synthesized. The derivatives were characterized by Fourier transform infrared spectroscopy and 13C solid state nuclear magnetic resonance spectroscopy, which indicated that the crosslinking degrees ranged from 0 to 7.4%. The permeabilities of various plant nutrients, including macroelements (N, P, K), microelements (Zn2+ and Cu2+), and a plant growth regulator (naphthylacetic acid), were varied by moderate changes in crosslinking degree, indicating that the controlled-release properties can be regulated in this way. The film-forming ability of native chitosan was maintained, whilst mechanical properties, hydrophobicity and controlled permeability were improved. These dramatic improvements occurred with a small amount of added suberoyl chloride; excessive crosslinking led to membranes with unwanted poor permeability. Thus, both the mechanical properties and permeability of the crosslinked membrane can be optimized