Background
Grain size is a key determinant of grain weight and a trait having critical influence on grain quality in rice. While increasing evidences are shown for the importance of minor-effect QTL ...in controlling complex traits, the attention has not been given to grain size until recently. In previous studies, five QTL having small effects for grain size were resolved on the long arm of chromosome 1 using populations derived from
indica
rice cross Zhenshan 97///Zhenshan 97//Zhenshan 97/Milyang 46. One of them,
qTGW1.2c
that was located in a 2.1-Mb region, was targeted for fine-mapping in the present study.
Results
Firstly, the
qTGW1.2c
region was narrowed down into 1.1 Mb by determining genotypes of the cross-over regions using polymorphic markers newly developed. Then, one BC
2
F
9
plant that was only heterozygous in the updated QTL region was identified. A total of 12 populations in generations from BC
2
F
11:12
to BC
2
F
15:16
were derived and used for QTL mapping. Two QTL linked in a 460-kb region were separated. The
qGS1-35.2
was delimited into a 57.7-kb region, containing six annotated genes of which five showed nucleotide polymorphisms between the two parental lines. Quantitative real-time PCR detected expression differences between near isogenic lines for
qGS1-35.2
at three of the six annotated genes. This QTL affected grain length and width with opposite allelic directions, exhibiting significant effect on ratio of grain length to width but showing little influence on yield traits. The other QTL,
qGW1-35.5
, was located within a 125.5-kb region and found to primarily control grain width and consequently affect grain weight.
Conclusions
Our work lays a foundation for cloning of two minor QTL for grain size that have potential application in rice breeding. The
qGS1-35.2
could be used to modify grain appearance quality without yield penalty because it affects grain shape but hardly influences grain yield, while
qGW1-35.5
offers a new gene recourse for enhancing grain yield since it contributes to grain size and grain weight simultaneously.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We achieved chemoselective synthesis of α-alkylated arylacetonitriles and acetamides by combining Ir complex-catalysed direct coupling of alcohols and nitriles by a simple adjustment of the base. ...Methanol and ethanol performed well as the alkylating reagents. This method of acetonitrile alkylation provided a novel approach for carbon chain extension.
Cp*IrCl
2
2
with a phosphine-free ligand α,α,α-terpyridine shows high catalytic performance in chemodivergent synthesis of α-alkylated arylacetonitriles in the presence of K
2
CO
3
and α-alkylated acetamides in the presence of
t
BuOK, respectively.
The direct asymmetric Mannich reaction of glycine Schiff bases with N‐tosylimines has been developed with the tetrakis(acetonitrile)copper(I) tetrafluoroborate Cu(CH3CN)4BF4/TF‐BiphamPhos complex. ...This catalytic system performs well over a broad range of substrates, furnishing anti‐adducts of various α,β‐diamino acid esters in good yields with up to 94:6 diastereoselectivity and 97% enantioselectivity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Oral hygiene and the alteration of the oral microbiome have been linked to nasopharyngeal carcinoma (NPC). This study aimed to investigate whether the oral microbiome plays a mediating role in the ...relationship between oral hygiene and NPC, and identify differential microbial taxonomies that potentially mediated this association. We conducted a case-control study that involved 218 NPC patients and 192 healthy controls. The 16S rRNA gene sequencing of the V4 region was performed to evaluate the composition of the oral microbiome. Mediation analysis was applied to explore the relationship among oral hygiene, the oral microbiome and NPC. We found that dental fillings and poor oral hygiene score were associated with increased risks of NPC (OR = 2.51 (1.52-4.25) and OR = 1.54 (1.02-2.33)). Mediation analysis indicated that dental fillings increased the risk of NPC by altering the abundance of
,
,
and
. In addition,
also mediated the association between oral hygiene score and the risk of NPC. Our study confirmed that poor oral hygiene increased the risk of NPC, which was partly mediated by the oral microbiome. These findings might help us to understand the potential mechanism of oral hygiene influencing the risk of NPC via the microbiome.
Flexible thermoelectric materials are presented with potential applications in electronic devices and energy conversion due to their convenient preparation, good flexibility, and various forms. ...However, as ductility is rarely observed in inorganic semiconductors and ceramic insulators, reports on applications of inorganic oxide materials in flexible thermoelectric materials are sparse. Here, we report a new method for the synthesis of a flexible Na1.4Co2O4 thermoelectric material based on Na1.4Co2O4 bulk materials, which are prepared by a self-flux method and painted on print paper. Seebeck coefficient and power factor of the obtained thermoelectric material are 78–102 μVK-1 and 159–223 μWm−1K−2, respectively, in a temperature range of 303–522 K, which are superior to those values of other conductive polymers and their compounds. More interestingly, the n-type Na1.4Co2O4 flexible material is obtained in the painting process at higher pressure with Seebeck coefficients of −109 to −183 μVK−1 in a temperature range of 303–522 K. The convenient preparation method of these novel flexible thermoelectric materials may be expanded to the synthesis of other flexible thermoelectric materials, which will be the focus of future work.
Display omitted
•A flexible Na1.4Co2O4 thermoelectric material was obtained by novel method.•High thermoelectric performance was achieved in the flexible Na1.4Co2O4.•The n-type NaxCo2O4 flexible thermoelectric material is first discovered.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aberrant expression of the RON receptor tyrosine kinase is a pathogenic feature and a validated drug target in various types of cancers. Currently, therapeutic antibodies targeting RON for cancer ...therapy are under intensive evaluation. Here we report the development and validation of a novel humanized anti-RON antibody-drug conjugate for cancer therapy.
Antibody humanization was achieved by grafting sequences of complementarity-determining regions from mouse monoclonal antibody Zt/g4 into human IgG1/κ acceptor frameworks. The selected humanized Zt/g4 subclone H1L3 was conjugated with monomethyl auristatin E using a dipeptide linker to form H-Zt/g4-MMAE. Pharmacokinetic analysis of H-Zt/g4-MMAE was determined using hydrophobic interaction chromatography and a MMAE ADC ELISA kit. Biochemical and biological assays were used for measuring RON expression, internalization, cell viability and death. Therapeutic efficacies of H-Zt/g4-MMAE were validated in vivo using three pancreatic cancer xenograft models. Toxicological activities of H-Zt/g4-MMAE were determined in mouse and cynomolgus monkey.
H-Zt/g4-MMAE had a drug to antibody ratio of 3.77:1 and was highly stable in human plasma with a dissociation rate less than 5% within a 20 day period. H-Zt/g4-MMAE displayed a favorable pharmacokinetic profile in both mouse and cynomolgus monkey. In vitro, H-Zt/g4-MMAE induced RON internalization, which results in killing of pancreatic cancer cells with IC
values at 10-20 nM. In vivo, H-Zt/g4-MMAE inhibited pancreatic cancer xenograft growth with tumoristatic concentrations at 1~3 mg/kg bodyweight. Significantly, H-Zt/g4-MMAE eradicated tumors across multiple xenograft models regardless their chemoresistant and metastatic statuses. Moreover, H-Zt/g4-MMAE inhibited and eradicated xenografts mediated by pancreatic cancer stem-like cells and by primary cells from patient-derived tumors. Toxicologically, H-Zt/g4-MMAE is well tolerated in mice up to 60 mg/kg. In cynomolgus monkey, H-Zt/g4-MMAE up to 30 mg/kg had a manageable and reversible toxicity profile.
H-Zt/g4-MMAE is superior in eradication of pancreatic cancer xenografts with favorable pharmacokinetic profiles and manageable toxicological activities. These findings warrant the transition of H-Zt/g4-MMAE into clinical trials in the future.
Chemoradiation-induced hearing loss (CRIHL) is one of the most devasting side effects for nasopharyngeal carcinoma (NPC) patients, which seriously affects survivors’ long-term quality of life. ...However, few studies have comprehensively characterized the risk factors for CRIHL. In this study, we found that age at diagnosis, tumor stage, and concurrent cisplatin dose were positively associated with chemoradiation-induced hearing loss. We performed a genome-wide association study (GWAS) in 777 NPC patients and identified rs1050851 (within the exon 2 of
NFKBIA
), a variant with a high deleteriousness score, to be significantly associated with hearing loss risk (HR = 5.46, 95% CI 2.93–10.18,
P
= 9.51 × 10
–08
). The risk genotype of rs1050851 was associated with higher
NFKBIA
expression, which was correlated with lower cellular tolerance to cisplatin. According to permutation-based enrichment analysis, the variants mapping to 149 hereditary deafness genes were significantly enriched among GWAS top signals, which indicated the genetic similarity between hereditary deafness and CRIHL. Pathway analysis suggested that synaptic signaling was involved in the development of CRIHL. Additionally, the risk score integrating genetic and clinical factors can predict the risk of hearing loss with a relatively good performance in the test set. Collectively, this study shed new light on the etiology of chemoradiation-induced hearing loss, which facilitates high-risk individuals’ identification for personalized prevention and treatment.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Trifluoromethylated pyrrolidines have been synthesized via catalytic asymmetric 1,3-dipolar cycloaddition with excellent stereoselectivity for the first time. Epimerization of the endo-pyrrolidines ...obtained from cis-4,4,4-trifluorocrotonate into the exo-pyrrolidines was also revealed.
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