Identified novel heterozygous HTRA1 pathogenic variants in Chinese patients with HTRA1-associated dominant cerebral small vessel disease.

Background: Homozygous and compound heterozygous mutations in HTRA1 cause cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Recently, heterozygous pathogenic variants in HTRA1 were described in patients with autosomal dominant cerebral small vessel disease (CSVD). Here, we investigated the genetic variants in a cohort of Chinese patients with CSVD. Methods: A total of 95 Chinese index patients with typical characteristics of CSVD were collected. Whole exome sequencing was performed in the probands, followed by Sanger sequencing. Pathogenicity prediction software was applied to evaluate the pathogenicity of the identified variants. Results: We detected five heterozygous HTRA1 pathogenic variants in five index patients. These pathogenic variants included four known variants (c.543delT, c.854C>T, c.889G>A, and c.824C>T) and one novel variant (c.472 + 1G>A). Among them, c.854C>T, c.824C>T, and c.472 + 1G>A have never been reported in China and c.889G>A was once reported in homozygous but never in heterozygous. Three of them were distributed in exon 4, one in exon 2, and another splicing variant in intron 1. Four out of five probands presented typical features of CARASIL but less severe. The common clinical features included lacunar infarction, cognitive decline, alopecia, and spondylosis. All of them showed leukoencephalopathy, and the main involved cerebral area include periventricular and frontal area, centrum semiovale, thalamus, and corpus callosum. Anterior temporal lobes and external capsule involvement were also observed. Three probands had intracranial microbleeds. Conclusion: Our study expanded the mutation spectrum of HTRA1, especially in Chinese populations, and provided further evidence for "hot regions" in exon 1-4, especially in exon 4, in heterozygous HTRA1 pathogenic variants. Our work further supported that patients with heterozygous HTRA1 pathogenic variants presented with similar but less-severe features than CARASIL but in an autosomal dominantly inherited pattern.

Spastic paraplegia as the predominant phenotype in a cohort of Chinese patients with adrenoleukodystrophy.

BACKGROUND: X-linked adrenoleukodystrophy (ALD) is one of the most common peroxisomal disorders characterized by abnormal accumulation of very long-chain fatty acids (VLCFA) in plasma and tissues and caused by mutations within ABCD1. Clinically, ALD present with various phenotypes, ranging from asymptomatic type to rapidly progressive childhood cerebral form. However, no remarkable abnormality in cerebral white matter usually makes it difficult to distinguish adult ALD from hereditary spastic paraplegia (HSP). METHODS: We analyzed the features of seven Chinese ALD patients who had a primary phenotype of spastic paraplegia. Sequencing was performed in the probands and their familial members. Detailed clinical, VLCFAs test, hormone test, magnetic resonance imaging, and electromyogram are presented. RESULTS: We reported seven ALD patients from a Chinese cohort of 142 HSP patients. Genetic investigations revealed five known ABCD1 mutations (c.346G>C, c.521A>G, c.829G>T, c.1415_1416delAG, and c.1849C>T) and two novel mutations (c.454C>G, c.1452_1482del). Further auxiliary testing revealed that they had higher VLCFA and/or adrenal insufficiency. CONCLUSIONS: Our findings expand the mutation spectrum of ABCD1 and indicate that ALD represent a significant portion (4.9%, 7/142) of the spastic paraplegia entities. ALD should be considered in male patients with spastic paraplegia, even if there was no positive family history.

Clinical and genetic characterization of a cohort of Chinese patients with hereditary spastic paraplegia.

Pedigree chart of hereditary spastic paraplegia (HSP) patients and chromatogram of novel mutations. A. Pedigree chart of 12 Chinese HSP families with mutation. Squares indicate males; circles indicate females; the black symbols indicate affected individuals; arrows indicate the probands; and asterisks indicate the individual with mutation.B. Chromatogram of six novel mutations identified in our cohort. The upper panel in chromatogram depicts the reference sequence. The lower panel represents heterozygous mutated sequence.

Highly Efficient Organic Photocatalyst with Full Visible Light Spectrum through π-π Stacking of TCNQ-PTCDI.

Self-assembled TCNQ-PTCDI composite photocatalysts can not only degrade phenol at a rate of 0.154 h-1, which is 10.4 times higher than that of pure PTCDI, but also produce oxygen at a rate of ∼14 µmol·g-1·h-1 without cocatalysts. The π-π interactions between TCNQ and PTCDI result in fast transfer of carriers and reduced carrier recombination. The interaction lowers the valence band and narrows the band gap, thus leading to a stronger oxidizability and a broad spectral response (∼730 nm). Moreover, the presence of TCNQ stabilizes the composite to decrease the accumulation of negative charge, which results in an excellent stability of the composite. The high catalytic activity can potentially be utilized in the fields of environmental and energy applications.

Polyaniline/Carbon Nitride Nanosheets Composite Hydrogel: A Separation-Free and High-Efficient Photocatalyst with 3D Hierarchical Structure.

A polyaniline (PANI)/carbon nitride nanosheets (CNNS) composite hydrogel with 3D hierarchical nanostructure is synthesized via in situ polymerization. The 3D hierarchical structure is robust and stable, making the composite hydrogel separation-free and easy to recycling. It is highly excellent in removing organic pollutant for PANI/CNNS composite hydrogel on account of the cooperation of adsorptive preconcentration and the following photocatalytic oxidation. Pollutants are first adsorbed and concentrated into the 3D hierarchical nanostructure of the composite hydrogel. Then the pollutants are in situ oxidized via photocatalysis. The promoted photocatalytic performance can be mainly ascribed to the outstanding interfacial charge separation and photoelectrochemical performance. A new idea of the construction of 3D hierarchical photocatalysts is presented, which can be applied in the sustainability field.