Bulk RNA Sequencing With Integrated Single-Cell RNA Sequencing Identifies BCL2A1 as a Potential Diagnostic and Prognostic Biomarker for Sepsis.

Background: Sepsis is one of the leading causes of morbidity and mortality worldwide in the intensive care unit (ICU). The prognosis of the disease strongly depends on rapid diagnosis and appropriate treatment. Thus, some new and accurate sepsis-related biomarkers are pressing needed and their efficiency should be carefully demonstrated. Methods: Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were applied to detect sepsis and monocyte/macrophage-related genes. Least absolute shrinkage and selection operator (LASSO) and random forest regression analyses were used in combination to screen out prognostic genes. Single-cell RNA sequence profiling was utilized to further verify the expression of these genes on a single cell level. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were also applied to verify the diagnostic value of the target biomarkers. Results: The intersections of the genes detected by differential expression and WGCNA analyses identified 141 overlapping candidate genes that were closely related to sepsis and macrophages. The LASSO and random forest regression analyses further screened out 17 prognostic genes. Single-cell RNA sequencing analysis detected that FCGR1A and BCL2A1 might be potential biomarkers for sepsis diagnosis and the diagnostic efficacy of BCL2A1 was further validated by ROC curve and DCA. Conclusions: It was revealed that BCL2A1 had good diagnostic and prognostic value for sepsis, and that it can be applied as a potential and novel biomarker for the management of the disease.

Genomic and biological characterization of vB_PvuS_Pm34, a novel lytic bacteriophage that infects Proteus vulgaris.

Proteus phage vB_PvuS_Pm34 (Pm34) isolated from the sewage, is a novel virus specific to Proteus vulgaris. Pm34 belonged to the family Siphovirodae with an icosahedron capsid head and a non-contractile tail. Its genome was 39,558 bp in length with a G + C content of 41.4%. Similarity analysis showed that Pm34 shared low identities of 27.6%-38.4% with any other Proteus phages, but had the 96% high identity with Proteus mirabilis AOUC-001. In the genome of Pm34, 70 open reading frames was deduced and 32 had putative functions including integrase and host lysis proteins. No tRNAs, antibiotic resistance and virulence genes were detected. Pm 34 presented a broad pH (4-8) and good temperature tolerance (<40 °C). This is the first report of the bacteriophage specific to P. vulgaris, which can enrich the knowledge of bacteriophages of Prouteus bacteria and provide the possibility for the alternative treatment of P. vulgaris infection.

A Self-Assembled Nanoindicator from Alizarin Red S-Borono-Peptide for Potential Imaging of Cellular Copper(II) Ions.

Recently, smart nanomaterials from peptide self-assembly have received extensive attention in the field of biological and medical applications. Through rationally designing the molecular structure, we constructed a borono-peptide that self-assembled into well-defined nanofibers. Relying on the specific recognition between the vicinal diol compound and boronic acid, a novel alizarin red S (ARS)-borono-peptide (BP) spherical nanoindicator was fabricated, accompanying with the emission of strong fluorescent signal. The fluorescent nanoindicator displayed an intense response to copper(II) ions and underwent the fluorescent "turn-off" due to the strong binding-induced displacement. Originating from the high selectivity toward copper(II) ions, good biocompatibility and cancer cell targeting, the nanoindicator offered the opportunity to image copper(II) ions in cancer cells via fluorescent change.

Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China.

Leprosy is a chronic infectious and neurological disease caused by Mycobacterium leprae, an unculturable pathogen with massive genomic decay and dependence on host metabolism. We hypothesized that mitochondrial genes PARL and PINK1 would confer risk to leprosy. Thirteen tag SNPs of PARL and PINK1 were analyzed in 3620 individuals with or without leprosy from China. We also sequenced the entire exons of PARL, PINK1 and PARK2 in 80 patients with a family history of leprosy by using the next generation sequencing technology (NGS). We found that PARL SNP rs12631031 conferred a risk to leprosy (Padjusted = 0.019) and multibacillary leprosy (MB, Padjusted = 0.020) at the allelic level. rs12631031 and rs7653061 in PARL were associated with leprosy and MB (dominant model, Padjusted < 0.05) at the genotypic level. PINK1 SNP rs4704 was associated with leprosy at the genotypic level (Padjusted = 0.004). We confirmed that common variants in PARL and PINK1 were associated with leprosy in patients underwent NGS. Furthermore, PARL and PINK1 could physically interact with each other and were involved in the highly connected network formed by reported leprosy susceptibility genes. Together, our results showed that PARL and PINK1 genetic variants are associated with leprosy.

Fine mapping of the GWAS loci identifies SLC35D1 and IL23R as potential risk genes for leprosy.

BACKGROUND: Previous genome-wide association study (GWAS) identified two new leprosy associated loci (1p31.3 [rs3762318] and 6q24.3 [rs2275606]). However, there were insufficient validations in independent populations. OBJECTIVE: To validate the association and to map the potentially causal variants/genes underlying the association between the confirmed GWAS hit and leprosy. METHODS: We genotyped 10 variants in the regions encompassing the two loci in 1110 Han Chinese subjects with and without leprosy, followed by expression quantitative trait loci (eQTL), mRNA expression profiling, and network analysis. We further sequenced the exon region of four genes that were located in the confirmed GWAS hit region in 80 leprosy patients and 99 individuals without leprosy. RESULTS: We validated the positive association of rs3762318 with multibacillary leprosy (P=7.5×10-4), whereas the association of rs2275606 could not be validated. eQTL analysis showed that both the GWAS locus rs3762318 and one surrounding positively associated SNP rs2144658 (P=1.8×10-3) significantly affected the mRNA expression of a nearby gene SLC35D1, which might be involved in metabolism. Moreover, SLC35D1 was differentially expressed in skin tissues of leprosy patients, and the differential expression pattern was consistent among leprosy subtypes. Rare damaging missense variants in IL23R were significantly enriched in leprosy patients. CONCLUSION: Our results supported the positive association between the GWAS reported rs3762318 and leprosy, and SLC35D1 and IL23R might be the causal genes.

No association of the LRRK2 genetic variants with Alzheimer's disease in Han Chinese individuals.

The leucine-rich repeat kinase-2 (LRRK2) gene has been regarded as 1 of the most common genetic causes of Parkinson's disease (PD). We hypothesized that LRRK2-susceptible allele(s) for PD might pose a risk for Alzheimer's disease (AD). In this study, we screened 12 LRRK2 gene variants in 2 independent cohorts from southwestern China (341 AD patients and 435 normal individuals) and eastern China (297 AD patients and 384 normal individuals), to discern the potential association between this gene and AD. No variant was identified to be associated with AD in either case-control sample. As both of the cohorts were of Han Chinese origin, we combined the LRRK2 variant data for the 2 sample sets together (a total of 638 AD patients and 819 normal individuals) and still found no association between the LRRK2 gene and AD, suggesting that LRRK2 gene variants may not affect the development of AD in Han Chinese individuals.

A mononuclear cobalt(II)-dithienylethene complex showing slow magnetic relaxation and photochromic behavior.

Mononuclear complex Co(hpbdti)2·3CH3OH (1) was synthesized [hpbdtiH = 2-(2-hydroxyphenyl)-4,5-bis(2,5-dimethyl(3-thienyl))-1H-imidazole], showing multiple-step field-induced slow magnetic relaxation behaviors, and photochromic properties in CH2Cl2-CH3CN solution.

Mononuclear lanthanide complexes incorporating an anthracene group: structural modification, slow magnetic relaxation and multicomponent fluorescence emissions in Dy compounds.

Four mononuclear lanthanide complexes, [Ln(hfac)3(depma)(H2O)] [Ln(III) = Dy (1), Gd (2)], [Dy(hfac)3(depma)2]2·H2O (3) and [Gd(hfac)3(depma)2]·2H2O (4), have been obtained (hfac = hexafluoroacetylacetonate, depma = 9-diethylphosphonomethyl anthracene) by using one (for 1 and 2) or two (for 3 and 4) depma molecules to substitute coordination water molecules of Ln(hfac)3(H2O)2. It was found that the number of introduced depma ligands can modify the coordination geometry of Ln(iii) ions, showing a distorted biscapped triangular prism geometry in isostructural 1 and 2 and a distorted square-antiprismatic geometry in 3 and 4. Magnetic studies reveal that both 1 and 3 show field-induced slow magnetic relaxation under the applied dc field of 1000 Oe. The solid-state fluorescence measurements indicate the presence of multicomponent emissions in 1 and 3, including ligand-centered (LC) emissions from hfac and depma, and yellow emission from Dy(III) ions and only ligand-centered (LC) emissions in 2 and 4.

Phosphonates containing 8-hydroxyquinoline moiety and their metal complexes: structures, fluorescent and magnetic properties.

Two kinds of solid-state structures of 5-phosphonomethyl-8-hydroxyquinoline (5pm8hqH3) have been obtained, namely 1·HCl·H2O and 1·H2O, involving different hydrogen bonds and/or aromatic stacking interactions. As a derivative of 5pm8hqH3, 5-phosphonomethyl-8-(carboxymethoxy)quinoline (5pm8cmoqH3) was synthesized. Based on 5pm8hqH3 and 5pm8cmoqH3, three new metal phosphonates have been hydrothermally prepared, including Zn(5pm8hqH)(H2O)·H2O (2), Cu(5pm8cmoqH)·2H2O (3) and Fe(5pm8cmoqH) (4), exhibiting layered structures for 2 and 4, and a three-dimensional open framework for 3. The 8-hydroxyquinoline moieties in 1·H2O and 2-4 exhibit three kinds of interesting aromatic stacking modes, including pyridine ring-pyridine ring stacking between a pair of moieties, double benzene ring-pyridine ring stacking between a pair of moieties and alternating benzene ring-benzene ring and pyridine ring-pyridine ring stacking among a number of moieties in the layered structure. The solid-state fluorescence measurements indicate the emissions of 1·HCl·H2O and 1·H2O are significantly different due to their distinct packing structures. Compound 2 exhibits both ligand-centered (LC) and ligand-to-metal charge transition (LMCT) emissions. Magnetic studies reveal dominant antiferromagnetic interactions in 3 and 4.

Genetic variants of the MRC1 gene and the IFNG gene are associated with leprosy in Han Chinese from Southwest China.

Leprosy is an ancient infectious disease, with over 200,000 affected people (mainly in Asia and Africa) being registered annually. Genetic factors may confer susceptibility to this disease. In the present study, we genotyped 12 genetic variants of the MRC1 gene and the IFNG gene in 527 Han Chinese with leprosy and 583 healthy individuals from Yunnan, China, to discern potential association of these two genes with leprosy. In particular, we aimed to validate the recently reported association of MRC1 variant rs1926736 (p.G396S) and IFNG variant rs2430561 (+874 T>A) with leprosy, which were initially observed in Vietnamese and Brazilian populations, respectively. Our results failed to confirm the reported association between variants rs1926736 and rs2430561 and leprosy in Han Chinese. However, we found that variants rs692527 (P = 0.022) and rs34856358 (P = 0.022) of the MRC1 gene were associated with paucibacillary leprosy, and rs3138557 of the IFNG gene was significantly associated with multibacillary leprosy. The exact role of the MRC1 gene and the IFNG gene in leprosy awaits future study.