Identification of ferroptosis-related gene signature for tuberculosis diagnosis and therapy efficacy.

Diagnosis of tuberculosis remains a challenge when microbiological tests are negative. Immune cell atlas of patients with tuberculosis and healthy controls were established by single-cell transcriptome. Through integrated analysis of scRNA-seq with microarray and bulk RNA sequencing data, a ferroptosis-related gene signature containing ACSL4, CTSB, and TLR4 genes that were associated with tuberculosis disease was identified. Four gene expression datasets from blood samples of patients with tuberculosis, latent tuberculosis infection, and healthy controls were used to assess the diagnostic value of the gene signature. The areas under the ROC curve for the combined gene signature were 1.000, 0.866, 0.912, and 0.786, respectively, in differentiating active tuberculosis from latent infection. During anti-tuberculosis treatment, the expression of the gene signature decreased significantly in cured patients with tuberculosis. In conclusion, the ferroptosis-related gene signature was associated with tuberculosis treatment efficacy and was a promising biomarker for differentiating active tuberculosis from latent infection.

Disseminated tuberculosis is associated with impaired T cell immunity mediated by non-canonical NF-κB pathway.

OBJECTIVES: The mechanism that leads to disseminated tuberculosis in HIV-negative patients is still largely unknown. T cell subsets and signaling pathways that were associated with disseminated tuberculosis were investigated. METHODS: Single-cell profiling of whole T cells was performed to identify T cell subsets and enriched signaling pathways that were associated with disseminated tuberculosis. Flow cytometrical analysis and blocking experiment were used to investigate the findings obtained by transcriptome sequencing. RESULTS: Patients with disseminated tuberculosis had depleted Th1, Tc1 and Tc17 cell subsets, and IFNG was the most down-regulated gene in both CD4 and CD8 T cells. Gene Ontology analysis showed that non-canonical NF-κB signaling pathway, including NFKB2 and RELB genes, were significantly down-regulated and were probably associated with disseminated tuberculosis. Expression of several TNF superfamily ligands and receptors, such as LTA and TNF genes, were suppressed in patients with disseminated tuberculosis. Blocking of TNF-α and soluble LTα showed that TNF-α was involved in IFN-γ production and LTα influenced TNF-α expression in T cells. CONCLUSIONS: Impaired T cell IFN-γ response mediated by suppression of TNF and non-canonical NF-κB signaling pathways might be responsible for disseminated tuberculosis.

Natural variation in a CENTRORADIALIS homolog contributed to cluster fruiting and early maturity in cotton.

BACKGROUND: Plant architecture and the vegetative-reproductive transition have major impacts on the agronomic success of crop plants, but genetic mechanisms underlying these traits in cotton (Gossypium spp.) have not been identified. RESULTS: We identify four natural mutations in GoCEN-Dt associated with cluster fruiting (cl) and early maturity. The situ hybridization shows that GhCEN is preferentially expressed in cotton shoot apical meristems (SAM) of the main stem and axillary buds. Constitutive GhCEN-Dt overexpression suppresses the transition of the cotton vegetative apex to a reproductive shoot. Silencing GoCEN leads to early flowering and determinate growth, and in tetraploids causes the main stem to terminate in a floral bud, a novel phenotype that exemplifies co-adaptation of polyploid subgenomes and suggests new research and/or crop improvement approaches. Natural cl variations are enriched in cottons adapted to high latitudes with short frost-free periods, indicating that mutants of GoCEN have been strongly selected for early maturity. CONCLUSION: We show that the cotton gene GoCEN-Dt, a homolog of Antirrhinum CENTRORADIALIS, is responsible for determinate growth habit and cluster fruiting. Insight into the genetic control of branch and flower differentiation offers new approaches to develop early maturing cultivars of cotton and other crops with plant architecture appropriate for mechanical harvesting.

Enriching an intraspecific genetic map and identifying QTL for fiber quality and yield component traits across multiple environments in Upland cotton (Gossypium hirsutum L.).

Cotton is a significant commercial crop that plays an indispensable role in many domains. Constructing high-density genetic maps and identifying stable quantitative trait locus (QTL) controlling agronomic traits are necessary prerequisites for marker-assisted selection (MAS). A total of 14,899 SSR primer pairs designed from the genome sequence of G. raimondii were screened for polymorphic markers between mapping parents CCRI 35 and Yumian 1, and 712 SSR markers showing polymorphism were used to genotype 180 lines from a (CCRI 35 × Yumian 1) recombinant inbred line (RIL) population. Genetic linkage analysis was conducted on 726 loci obtained from the 712 polymorphic SSR markers, along with 1379 SSR loci obtained in our previous study, and a high-density genetic map with 2051 loci was constructed, which spanned 3508.29 cM with an average distance of 1.71 cM between adjacent markers. Marker orders on the linkage map are highly consistent with the corresponding physical orders on a G. hirsutum genome sequence. Based on fiber quality and yield component trait data collected from six environments, 113 QTLs were identified through two analytical methods. Among these 113 QTLs, 50 were considered stable (detected in multiple environments or for which phenotypic variance explained by additive effect was greater than environment effect), and 18 of these 50 were identified with stability by both methods. These 18 QTLs, including eleven for fiber quality and seven for yield component traits, could be priorities for MAS.

Synthesis and optoelectronic properties of a carbazole-modified platinum(II) complex in polymer light-emitting devices.

To improve opto-electronic properties and efficiently suppress excimer emission, a phenylpyridine (ppy)-based platinum(II) complex (C(16)OCz-ppy)Pt(acac) was synthesized and characterized, where C(16)OCz-ppy is a 2-phenylpyridine derivative appending a carbazole moiety and three hexadecyloxy methyl units in the parent phenylpyridine, and acac is acetylacetone. This carbazole-modified platinum(II) complex exhibited good thermal stability and three times higher photoluminescent quantum yield than its parent (2-phenylpyridine-C(2),N)(2,4-pentanedionato-O,O)platinum(II) complex [(ppy)Pt(acac)]. Single-emissive-layer polymer light-emitting devices using (C(16)OC(Z)-ppy)Pt(acac) as dopant and a blend of poly(N-vinylcarbazole) and 2-(4-biphenyl)-5-(4-tert-butylphenyl)-1,3,4-oxadiazole as host matrix presented a maximum current efficiency of 1.51 cd A(-1), which was 1.5 times higher than that from the (ppy)Pt(acac)-doped device with the same device structure. Little excimer emission and minor aggregation emission were observed in the (C(16)OC(Z)-ppy)Pt(acac)-doped PLEDs at different dopant concentrations and applied voltages. This work indicates that introducing a carbazole and three hexadecyloxy methyl groups into the planar platinum(II) complex can reduce molecular aggregation and excimer emissions, thus resulting in high luminance and stable EL spectra in comparison with the parent (ppy)Pt(acac).