Experimental and computational models to investigate intestinal drug permeability and metabolism.

Oral administration is the preferred route for drug administration that leads to better therapy compliance. The intestine plays a key role in the absorption and metabolism of oral drugs, therefore, new intestinal models are being continuously proposed, which contribute to the study of intestinal physiology, drug screening, drug side effects, and drug-drug interactions.Advances in pharmaceutical processes have produced more drug formulations, causing challenges for intestinal models. To adapt to the rapid evolution of pharmaceuticals, more intestinal models have been created. However, because of the complexity of the intestine, few models can take all aspects of the intestine into account, and some functions must be sacrificed to investigate other areas. Therefore, investigators need to choose appropriate models according to the experimental stage and other requirements to obtain the desired results.To help researchers achieve this goal, this review summarised the advantages and disadvantages of current commonly used intestinal models and discusses possible future directions, providing a better understanding of intestinal models.

Case report: Bilateral sudden deafness in acute middle cerebellar peduncle infarction: central or peripheral?

Background: The middle cerebellar peduncle (MCP) is the most common site associated with hearing impairment in acute ischaemic stroke. Narrowing or occlusion of the vertebrobasilar artery due to atherosclerosis is thought to be the main pathogenesis of MCP infarction. Most previous reports of MCP infarction have not been clear whether the patient's hearing impairment is localized to the center or periphery. Case presentation: We report 44-year-old man with vertigo, tinnitus, and bilateral sudden sensorineural hearing loss (SSNHL) as the first symptoms. Pure Tone Audiogram revealed complete hearing loss in both ears. Acute bilateral MCP infarction was diagnosed by repeated brain magnetic resonance imaging (MRI). The brainstem auditory evoked potential (BAEP) and the electrocochleography were normal. The otoacoustic emissions showed binaural cochlear dysfunctions. After the antiplatelet, lipid-lowering, steroids and hyperbaric oxygen therapy, the pure-tone average (PTA) showed a clear improvement with 67 decibels (dB) on the right and 73 dB on the left at the 3-month follow-up. Conclusion: Vertebrobasilar diseases due to atherosclerosis should be routinely considered in middle-aged and elderly patients with vascular risk factors and bilateral hearing loss. Bilateral SSNHL can be a prodrome of acute MCP infarction and it can be peripheral. Brain MRI, brain magnetic resonance angiogram (MRA), brain and neck computed tomography angiography (CTA), BAEP, otoacoustic emissions, and Pure Tone Audiogram help to localize and qualify the diagnosis. Bilateral SSNHL localized to the periphery usually improves better and has a good prognosis. Early detection of hearing loss and intervention can help patients recover.

Exposure to parks through the lens of urban mobility.

This work presents a portable framework to estimate potential park demand and park exposure through bipartite weighted networks. We use mobility information and open spatial information. Mobility information comes in the form of daily activities sampled from a model based on Call Detail Records (CDR). Spatial information comprise parks represented through OpenStreetMaps polygons and census tracts from the 2010 decennial US Census. The framework summarizes each city's information into one bipartite weighted network with the link weights representing the number of potential visits to a park from each census tract on an average weekday. We compare park exposure and park demand in Greater Los Angeles and Greater Boston in a pre-pandemic scenario. The park exposure of a census tract is calculated as the number of parks surrounding the daily activities of its inhabitants. The demand of a park is calculated as the number of daily activities surrounding it. We find that both cities' distribution of park exposure have similar shape with Boston having a higher average. On the other hand, the distribution of park demand is very similar in both cities, although their park spatial distributions are different. We include racial/ethnic information from the Census to explore how the park exposure connects tracts of different racial/ethnic groups. We associate parks to racial/ethnic groups based on the number of visitors from each group. Parks within minorities' tracts are mostly used by majority groups. Finally, through detecting communities in the network, we find that park exposure connects the cities locally, linking parks to their tracts nearby. Furthermore, we find a significant spatial correlation between network communities and different racial/ethnic composition in Los Angeles. This way, patterns of park exposure reproduce the separation among demographic groups of the city. Supplementary Information: The online version contains supplementary material available at 10.1140/epjds/s13688-022-00351-9.

Total synthesis of conosilane A via a site-selective C-H functionalization strategy.

The first total synthesis of conosilane A, a densely oxygenated nonisoprenoid sesquiterpene, has been achieved through stereoselective intramolecular radical cyclization and double utilization of site-selective C-H functionalization as key steps, thus simplifying the synthetic endeavors in natural product synthesis.

Palladium-Promoted Neutral 1,4-Brook Rearrangement/Intramolecular Allylic Cyclization Cascade Reaction: A Strategy for the Construction of Vinyl Cyclobutanols.

A cascade reaction to build vinyl cyclobutanol rings through activation of vinyl epoxides by palladium, followed by 1,4-Brook rearrangement and intramolecular cyclization with a palladium complex of the resulting carbon anion, is described. Through this cascade reaction, several highly substituted cyclobutanol substrates were achieved in good yields with high stereoselectivities.

Bioinspired Collective Syntheses of Iboga-Type Indole Alkaloids.

We present the application of a bioinspired collective synthesis strategy in the total syntheses of seven iboga-type indole alkaloids: (±)-tabertinggine, (±)-ibogamine, (±)-ibogaine, (±)-ibogaine hydroxyindolenine, (±)-3-oxoibogaine hydroxyindolenine, (±)-iboluteine, and (±)-ervaoffines D. In particular, tabertinggine and its congeners serve as iboga precursors for the subsequent biomimetic transformations into other iboga-type alkaloids.

Domino intramolecular Diels-Alder reactions to construct a 6/6/5/5 fused tetracyclic framework.

Domino intramolecular Diels-Alder (IMDA) reactions towards the 6/6/5/5 fused tetracyclic natural products were developed in satisfactory yield and high stereoselectivity. Four rings, six contiguous stereocenters and four C-C bonds were formed in a single operation. 4-epi-Hydromitchellene B was also synthesised efficiently via this strategy.

Diels-Alder/oxidative aromatization approach towards the all-carbon DEF tricyclic skeleton of daphenylline.

Daphenylline is a recently isolated Daphniphyllum alkaloid with an unprecedented novel hexacyclic scaffold. In this study, the synthesis of the fused all-carbon DEF tricyclic skeleton of daphenylline has been accomplished. Key steps of the reported sequence involve Evans asymmetric allylation, aldol condensation, Diels-Alder reaction, and oxidative aromatization reactions. The developed strategy might lead to the total synthesis of daphenylline.