Clinical profile of fatal familial insomnia: phenotypic variation in 129 polymorphisms and geographical regions.

Objective: Elucidate the core clinical and genetic characteristics and identify the phenotypic variation between different regions and genotypes of fatal familial insomnia (FFI).

Methods: A worldwide large sample of FFI patients from our case series and literature review diagnosed by genetic testing were collected. The prevalence of clinical symptoms and genetic profile were obtained, and then the phenotypic comparison between Asians versus non-Asians and 129Met/Met versus 129Met/Val were conducted.

Three novel mutations in Chinese patients with -related leukoencephalopathy.

Background: -related encephalopathy refers to adult-onset leukodystrophy with neuroaxonal spheroids and pigmented glia (ALSP) due to mutations, which is a rare autosomal dominant white matter disease including two pathological entities, hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD). The aim of this study was to identify additional causative mutations in the gene and clarify their pathogenic effects.

Methods: Whole-exome sequencing was conducted for nine Chinese patients diagnosed with possible ALSP based on clinical and neuroimaging findings from March 2014 to June 2020 at Xuanwu Hospital (Beijing, China).

Diastereoselective Construction of Cyclopropane-Fused Tetrahydroquinolines via a Sequential [4 + 2]/[2 + 1] Annulation Reaction.

A sequential [4 + 2]/[2 + 1] annulation of α-aryl vinylsulfoniums with 2-aminochalcones and 2-(2-aminobenzylidene)-1-indene-1,3(2)-dione is reported that affords a series of cyclopropane-fused tetrahydroquinolines. The salient features of this novel and practical transformation include high efficiency, transition-metal-free nature, operational simplicity, and outstanding functional group tolerance.

Asymmetric dearomatization of 2-nitrobenzofurans by organocatalyzed one-step Michael addition to access 3,3'-disubstituted oxindoles.

An efficient enantioselective dearomatization of 2-nitrobenzofurans was realized via an organocatalyzed one-step Michael addition process. This method provides a facile strategy to access a range of structurally diverse 3,3'-disubstituted oxindoles, which feature an intriguing combination of two privileged motifs including 3-pyrrolyl-substituted-oxindoles and 2,3-dihydrobenzofurans substructures, in excellent results.

Expression of FXR and HRG and their clinicopathological significance in benign and malignant pancreatic lesions.

Aims: The following study examines the FXR and HRG expression in benign and malignant lesions of the pancreas and evaluates the association between FXR and HRG expression with clinicopathological features and prognosis of pancreatic cancer.

Materials And Methods: Immunohistochemistry of FXR and HRG was performed with EnVision™ in 106 pancreatic ductal adenocarcinoma (PDAC) specimens, 35 paracancer samples (2 cm away from the tumor, when possible or available), 55 benign lesions and 13 normal tissue samples.

Results: The percentage of cases with positive FXR and negative HRG expression was significantly higher in PDAC compared to pericancerous tissues, benign lesions and normal tissues (P<0.

Coumarin-3-formylpyrazoles as 3-carbon synthons in cyclocondensation for the synthesis of spiro-fused pentacyclic spirooxindoles.

Coumarin-3-formylpyrazoles have been synthesized and applied as 3-carbon synthons in reaction with 3-hydroxyoxindoles by using DABCO as the catalyst. A range of structurally diverse spiro-fused pentacyclic spirooxindoles, bearing a spirooxindole-γ-lactone and a 3,4-dihydrocoumarin substructure, could be smoothly obtained in good to excellent yields (up to 99%) with excellent diastereoselectivities (all cases >20 : 1 dr). The asymmetric version of this tandem reaction was preliminarily investigated by using chiral organocatalysts.

Catalytic asymmetric [4+2] cycloaddition of 1-((2-aryl)vinyl)naphthalen-2-ols with in situ generated ortho-quinone methides for the synthesis of polysubstituted chromanes.

An efficient asymmetric [4+2] cycloaddition of 1-((2-aryl)vinyl)naphthalen-2-ols and in situ generated ortho-quinone methides with chiral phosphoric acid as the catalyst was developed. This reaction enables the highly enantioselective synthesis of chiral polysubstituted chromanes bearing multiple contiguous stereogenic centers in excellent yields and stereoselectivities (up to 99% yield, >95 : 5 dr and >99% ee).

Enantioselective synthesis of isoquinoline-1,3(2H,4H)-dione derivatives via a chiral phosphoric acid catalyzed aza-Friedel-Crafts reaction.

A highly enantioselective aza-Friedel-Crafts reaction of structurally new ketimines with indoles and pyrrole is developed by using a chiral phosphoric acid as the catalyst. This protocol enables the first enantioselective synthesis of isoquinoline-1,3(2H,4H)-dione derivatives in good to excellent yields (up to 99% yield) and excellent enantioselectivities (up to >99% ee).

Phosphine-catalyzed dearomative (3 + 2) annulation of 2-nitrobenzofurans and nitrobenzothiophenes with allenoates.

An efficient Ph2PMe-catalyzed dearomative (3 + 2) annulation of 2-nitrobenzofurans, 2-nitrobenzothiophenes, and 3-nitrobenzothiophenes with allenoates has been developed. With the developed protocol, a series of structurally important cyclopenta[b]benzofurans and cyclopenta[b]benzothiophenes were obtained in good to excellent yields (up to 98%) under mild conditions. In addition, preparative-scale experiments and transformations were conducted to exemplify the synthetic utility.

Inflammatory caspase-related pyroptosis: mechanism, regulation and therapeutic potential for inflammatory bowel disease.

As an essential part of programmed cell death, pyroptosis is an inflammatory response that is elicited upon infection by intracellular pathogens. Metabolic diseases, atherosclerosis and vital organ damage occur if pyroptosis is over-activated. Macrophages are the main cells that induce pyroptosis with the help of intracellular pattern-recognition receptors stimulated by danger signals and pathogenic microorganisms in the cytosol of host cells.

An organocatalytic asymmetric Mannich reaction of pyrazoleamides with cyclic trifluoromethyl ketimines: enantioselective access to dihydroquinazolinone skeletons.

An organocatalyzed asymmetric Mannich reaction of pyrazoleamides and cyclic trifluoromethyl ketimines with a chiral bifunctional amine-squaramide as the catalyst was developed. A wide range of trifluoromethyl dihydroquinazolinone derivatives bearing adjacent quaternary and tertiary stereogenic centers were readily obtained in good to excellent yields (up to 99%) with high diastereo- and enantioselectivities (up to 99% ee and >20 : 1 dr). The large scale experiment and transformation of the product have also been demonstrated.

A water-soluble and fast-response mitochondria-targeted fluorescent probe for colorimetric and ratiometric sensing of endogenously generated SO2 derivatives in living cells.

A novel water-soluble mitochondria-targeted ratiometric fluorescent probe (Cl-2) is presented. Cl-2 can respond selectively to SO2 derivatives within 1 min. Notably, Cl-2 can be used to monitor successfully the concentration change of endogenously generated SO2 derivatives in living cells.