An Investigation of Darwiche and Pearl's Postulates for Iterated Belief Update

Belief revision and update, two significant types of belief change, both focus on how an agent modify her beliefs in presence of new information. The most striking difference between them is that the former studies the change of beliefs in a static world while the latter concentrates on a dynamically-changing world. The famous AGM and KM postulates were proposed to capture rational belief revision and update, respectively. However, both of them are too permissive to exclude some unreasonable changes in the iteration. In response to this weakness, the DP postulates and its extensions for iterated belief revision were presented. Furthermore, Rodrigues integrated these postulates in belief update. Unfortunately, his approach does not meet the basic requirement of iterated belief update. This paper is intended to solve this problem of Rodrigues's approach. Firstly, we present a modification of the original KM postulates based on belief states. Subsequently, we migrate several well-known postulates for iterated belief revision to iterated belief update. Moreover, we provide the exact semantic characterizations based on partial preorders for each of the proposed postulates. Finally, we analyze the compatibility between the above iterated postulates and the KM postulates for belief update

Gut microbiome-derived hydrolases—an underrated target of natural product metabolism

In recent years, there has been increasing interest in studying gut microbiome-derived hydrolases in relation to oral drug metabolism, particularly focusing on natural product drugs. Despite the significance of natural product drugs in the field of oral medications, there is a lack of research on the regulatory interplay between gut microbiome-derived hydrolases and these drugs. This review delves into the interaction between intestinal microbiome-derived hydrolases and natural product drugs metabolism from three key perspectives. Firstly, it examines the impact of glycoside hydrolases, amide hydrolases, carboxylesterase, bile salt hydrolases, and epoxide hydrolase on the structure of natural products. Secondly, it explores how natural product drugs influence microbiome-derived hydrolases. Lastly, it analyzes the impact of interactions between hydrolases and natural products on disease development and the challenges in developing microbial-derived enzymes. The overarching goal of this review is to lay a solid theoretical foundation for the advancement of research and development in new natural product drugs and personalized treatment

Efficacy and safety of tigecycline monotherapy vs. imipenem/cilastatin in Chinese patients with complicated intra-abdominal infections: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Tigecycline, a first-in-class broad-spectrum glycylcycline antibiotic, has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections (cIAIs), including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria. In the current trial, tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs.</p> <p>Methods</p> <p>In this phase 3, multicenter, open-label study, patients were randomly assigned to receive IV tigecycline or imipenem/cilastatin for ≤2 weeks. The primary efficacy endpoints were clinical response at the test-of-cure visit (12-37 days after therapy) for the microbiologic modified intent-to-treat and microbiologically evaluable populations. Because the study was not powered to demonstrate non-inferiority between tigecycline and imipenem/cilastatin, no formal statistical analysis was performed. Two-sided 95% confidence intervals (CIs) were calculated for the response rates in each treatment group and for differences between treatment groups for descriptive purposes.</p> <p>Results</p> <p>One hundred ninety-nine patients received ≥1 dose of study drug and comprised the modified intent-to-treat population. In the microbiologically evaluable population, 86.5% (45 of 52) of tigecycline- and 97.9% (47 of 48) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment (12-37 days after therapy); in the microbiologic modified intent-to-treat population, cure rates were 81.7% (49 of 60) and 90.9% (50 of 55), respectively. The overall incidence of treatment-emergent adverse events was 80.4% for tigecycline vs. 53.9% after imipenem/cilastatin therapy (<it>P </it>< 0.001), primarily due to gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; <it>P </it>< 0.001) and vomiting (12.4% vs. 2.0%; <it>P </it>= 0.005).</p> <p>Conclusions</p> <p>Clinical cure rates for tigecycline were consistent with those found in global cIAI studies. The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI, as well as that observed in analyses of Chinese patients in those studies; no novel trends were observed.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00136201</p

Monitoring the Process and Characterizing Symptoms of Suckling Mouse Inoculation Promote Isolating Viruses from Ticks

Suckling mouse inoculation is an important method that has been used for years to isolate viruses from ticks; however, this method has usually been briefly described in the literature on a case-by-case basis upon successful isolation rather than providing extensive details. This study describes the procedure from preparation of tick homogenates to identification of virus isolation using the suckling mouse inoculation method. The transient and persistent features were characterized and the incidence of manifestations that developed in the suckling mice, especially in mice from which viruses were isolated, is reported. We identified 22 symptoms that developed in mice, including 13 transient symptoms that recovered by the end of the observation period and 7 persistent symptoms that the mice suffered from throughout the observation period. Persistent symptoms (lateral positioning and dead) and transient symptoms (malaise, emaciation, and difficulty turning over) were the main symptoms based on the high overall incidence. Moreover, we showed that mice from which viruses were isolated had a concentrated period and advanced days of disease onset. This study provides detailed information necessary for better use of suckling mouse inoculation to isolate viruses from ticks, which may benefit optimization of this method to identify, discover, and acquire tick-borne viruses

Coupling diversity across human behavior spaces

The heterogeneous nature of human behaviors contributes to the complexity of human-activated systems. Empirical observations and theoretical models reveal the temporal and spatial heterogeneity of many aspects of human behaviors, including social connections and geographic movements, while little is known whether and how human individual's behavioral diversities are correlated across different aspects. With statistical analysis on large-scale data of aligned online and offline human behaviors, we show that behavior spaces are coupled, independent from the specific choice of measurements. The coupling further expands to individual's direct and indirect social contacts. This finding provides insight into understanding homophily in different social systems and further improving the predictability of human online and offline behaviors

Comparison on the complete plastome genome between the wild and cultivated Angelica sinensis (Apiaceae), a famous Chinese medicinal herb

Angelica sinensis is one of the most widely used Chinese medicinal herb. It has been cultivated for over 900 years, and the wild resource has been on the verge of extinction owing to over-exploitation. In the present study, we assembled and characterized the complete chloroplast (cp) genomes of two wild and one cultivated individuals of A. sinensis for future genetic studies. These plastome genomes varied from 142,484 to 142,529 bp in size, and overall GC contents were about 37.5%. Phylogenetic analysis and comparison on the cp genome structure reveal that the wild A. sinensis sampled should not be the wild ancestor, but the escape of the cultivated

Rigid Body Brownian Dynamics as a Tool for Studying Ion Channel Blockers

Using a novel rigid body Brownian dynamics algorithm, we investigate how a spherically asymmetrical polyamine molecule, a branched analogue of spermine, interacts with the external vestibule of the voltage-gated potassium channel, Kv1.2. Simulations reveal that the blocker, with a charge of +4e, inserts one of its charged amine groups into the selectivity filter, while another forms a salt bridge with an aspartate residue located just outside the entrance of the pore. This binding mode mimics features of the binding of polypeptides such as the scorpion venom charybdotoxin to the channel. The potential of mean force constructed with Brownian dynamics is a reasonable match to that obtained from molecular dynamics simulations, with dissociation constants of 4.7 and 22 μM, respectively. The current-voltage relationships obtained with and without a blocker in the external reservoir show that the inward current is severely attenuated by the presence of the blocker, whereas the outward current is only moderately reduced. The computational molecular modeling technique we introduce here can provide detailed insights into ligand-channel interactions and can be used for rapidly screening potential blocker molecules