Spatial multi-omics at subcellular resolution via high-throughput in situ pairwise sequencing.

Technology for spatial multi-omics aids the discovery of new insights into cellular functions and disease mechanisms. Here we report the development and applicability of multi-omics in situ pairwise sequencing (MiP-seq), a method for the simultaneous detection of DNAs, RNAs, proteins and biomolecules at subcellular resolution. Compared with other in situ sequencing methods, MiP-seq enhances decoding capacity and reduces sequencing and imaging costs while maintaining the efficacy of detection of gene mutations, allele-specific expression and RNA modifications. MiP-seq can be integrated with in vivo calcium imaging and Raman imaging, which enabled us to generate a spatial multi-omics atlas of mouse brain tissues and to correlate gene expression with neuronal activity and cellular biochemical fingerprints. We also report a sequential dilution strategy for resolving optically crowded signals during in situ sequencing. High-throughput in situ pairwise sequencing may facilitate the multidimensional analysis of molecular and functional maps of tissues.

Application of postmortem MRI for identification of medulla oblongata contusion as a cause of death: a case report.

Whiplash injury is common in traffic accidents, and severe whiplash is characterized by cervical spinal cord injuries with cervical dislocation or fracture, that can be diagnosed by postmortem computed tomography (PMCT), postmortem magnetic resonance (PMMR), or conventional autopsy. However, for cervical spinal cord injury without fracture and dislocation, PMMR can be more informative because it provides higher resolution of soft tissues. We report the case of a 29-year-old male who died immediately following a traffic accident, in which the vehicle hit an obstacle at a high speed, causing deformation of the bumper and severe damage of the vehicle body. PMCT indicated no significant injuries or diseases related to death, but PMMR showed patchy abnormal signals in the medulla oblongata, and the lower edge of the cerebellar tonsil was herniated out of the foramen magnum. The subsequent pathological and histological results confirmed that death was caused by medulla oblongata contusion combined with cerebellar tonsillar herniation. Our description of this case of a rare but fatal whiplash injury in which there was no fracture or dislocation provides a better understanding of the potentially fatal consequences of cervical spinal cord whiplash injury without fracture or dislocation and of the underlying lethal mechanisms. Compared with PMCT, PMMR provides important diagnostic information in forensic practice for the identification of soft tissue injuries, and is therefore an important imaging modality for diagnosis of whiplash injury when there is no fracture or dislocation.

Application of Targeted Coronary Angiography in the Diagnosis of Sudden Cardiac Death.

OBJECTIVES: To diagnose coronary artery stenosis by using the postmortem computed tomography angiography (PMCTA), and to explore the diagnostic value of PMCTA in sudden cardiac death. METHODS: Six death cases were selected, and the contrast medium iohexol was injected under high pressure through femoral artery approach with 5F pigtail catheter to obtain coronary image data and then the data was analyzed. The results of targeted coronary imaging and coronary artery calcium score (CaS) were compared with the results of conventional autopsy and histopathological examination. RESULTS: The autopsy and histopathological examination of cases with coronary artery stenosis obtained similar results in targeted coronary angiography, with a diagnostic concordance rate of 83.3%. Targeted coronary angiography could effectively show coronary artery diseases, and the CaS was consistent with the results of conventional autopsy and histopathological examination. CONCLUSIONS: Targeted coronary angiography can be used as an effective auxiliary method for conventional autopsy in cases of sudden cardiac death.

The Impact of PM2.5 on the Host Defense of Respiratory System.

The harm of fine particulate matter (PM2.5) to public health is the focus of attention around the world. The Global Burden of Disease (GBD) Study 2015 (GBD 2015 Risk Factors Collaborators, 2016) ranked PM2.5 as the fifth leading risk factor for death, which caused 4.2 million deaths and 103.1 million disability-adjusted life-years (DALYs) loss, representing 7.6% of total global deaths and 4.2% of global DALYs. Epidemiological studies have confirmed that exposure to PM2.5 increases the incidence and mortality of respiratory infections. The host defense dysfunction caused by PM2.5 exposure may be the key to the susceptibility of respiratory system infection. Thus, this review aims to assess the impact of PM2.5 on the host defense of respiratory system. Firstly, we elaborated the epidemiological evidence that exposure to PM2.5 increases the risk of respiratory infections. Secondly, we summarized the experimental evidence that PM2.5 exposure increases the susceptibility of different pathogens (including bacteria and viruses) in respiratory system. Furthermore, here we discussed the underlying host defense mechanisms by which PM2.5 exposure increases the risk of respiratory infections as well as future perspectives.

Synthesis of N-aryl ß-amino acid derivatives via Cu(ii)-catalyzed asymmetric 1,4-reduction in air.

In the presence of the inexpensive and stable stoichiometric reductant polymethylhydrosiloxane (PMHS) as well as certain amounts of appropriate alcohol and base additives, the non-precious metal copper-catalyzed asymmetric 1,4-hydrosilylation of ß-aryl or ß-alkyl-substituted N-aryl ß-enamino esters was well realized to afford a diverse range of N-aryl ß-amino acid esters in high yields and excellent enantioselectivities (26 examples, 90-98% ee). This approach tolerated the handling of both catalyst and reactants in air without special precautions. The chiral products obtained have been successfully converted to the corresponding enantiomerically enriched ß-lactam and unprotected ß-amino acid ester, which highlighted the synthetic utility of the developed catalytic procedure.

A supramolecularly tunable chiral diphosphine ligand: application to Rh and Ir-catalyzed enantioselective hydrogenation.

A supramolecularly tunable chiral bisphosphine ligand bearing two pyridyl-containing crown ethers, (-) or (+)-Xyl-P16C6-Phos, was fabricated and utilized in the Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid esters and Ir-catalyzed asymmetric hydrogenation of quinolines in high yields with excellent enantioselectivities (90-99% ee). Up to a 22% enhancement in enantioselectivity was achieved by the addition of certain amounts of alkali ions (Li+, Na+ or K+), which could be selectively recognized and effectively complexed by the crown ethers on the chiral Xyl-P16C6-Phos.

Copper(II)-catalyzed enantioselective hydrosilylation of halo-substituted alkyl aryl and heteroaryl ketones: asymmetric synthesis of (R)-fluoxetine and (S)-duloxetine.

A set of reaction conditions has been established to facilitate the non-precious copper-catalyzed enantioselective hydrosilylation of a number of structurally diverse ß-, γ- or ε-halo-substituted alkyl aryl ketones and α-, ß- or γ-halo-substituted alkyl heteroaryl ketones under air to afford a broad spectrum of halo alcohols in high yields and good to excellent enantioselectivities (up to 99% ee). The developed procedure has been successfully applied to the asymmetric synthesis of antidepressant drugs (R)-fluoxetine and (S)-duloxetine, which highlighted its synthetic utility.