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A major and stable QTL cQSGR.sau.3D, which can explain 33.25% of the phenotypic variation in SGR, was mapped and validated, and cQSGR.sau.3D was found to be independent of GI. In this study, a recombinant inbred line (RIL) population containing 304 lines derived from the cross of Chuan-nong17 (CN17) and Chuan-nong11 (CN11) was genotyped using the Wheat55K single-nucleotide polymorphism array. A high-density genetic map consisting of 8329 markers spanning 4131.54 cM and distributed across 21 wheat chromosomes was constructed. QTLs for whole spike germination rate (SGR) were identified in multiple years. Six and fourteen QTLs were identified using the Inclusive Composite Interval Mapping-Biparental Populations and Multi-Environment Trial methods, respectively. A total of 106 digenic epistatic QTLs were also detected in this study. One of the additive QTLs, cQSGR.sau.3D, which was mapped in the region from 3.5 to 4.5 cM from linkage group 3D-2 on chromosome 3D, can explain 33.25% of the phenotypic variation in SGR and be considered a major and stable QTL for SGR. This QTL was independent of the seeds' germination traits, such as germination index. One Kompetitive Allele-Specific PCR (KASP) marker, KASP-AX-110772653, which is tightly linked to cQSGR.sau.3D, was developed. The genetic effect of cQSGR.sau.3D on SGR in the RIL and natural populations was successfully confirmed. Furthermore, within the interval in which cQSGR.sau.3D is located in Chinese Spring reference genomes, thirty-seven genes were found. cQSGR.sau.3D may provide new resources for pre-harvest sprouting resistance breeding of wheat in the future.

The efficient palladium-catalyzed synthesis of esters from readily available arenes has been developed. These C-H bond esterifications were achieved relying on the regioselective thianthrenation to generate the aryl-TT salts, which were treated as reactive electrophilic substrates to couple with phenol formate and

The coronavirus disease 2019 (COVID-19) pandemic and the measures taken by authorities to control its spread had altered human behavior and mobility patterns in an unprecedented way. However, it remains unclear whether the population response to a COVID-19 outbreak varies within a city or among demographic groups. Here we utilized passively recorded cellular signaling data at a spatial resolution of 1km × 1km for over 5 million users and epidemiological surveillance data collected during the SARS-CoV-2 Omicron BA.2 outbreak from February to June 2022 in Shanghai, China, to investigate the heterogeneous response of different segments of the population at the within-city level and examine its relationship with the actual risk of infection. Changes in behavior were spatially heterogenous within the city and population groups, and associated with both the infection incidence and adopted interventions. We also found that males and individuals aged 30-59 years old traveled more frequently, traveled longer distances, and their communities were more connected; the same groups were also associated with the highest SARS-CoV-2 incidence. Our results highlight the heterogeneous behavioral change of the Shanghai population to the SARS-CoV-2 Omicron BA.2 outbreak and the its effect on the heterogenous spread of COVID-19, both spatially and demographically. These findings could be instrumental for the design of targeted interventions for the control and mitigation of future outbreaks of COVID-19 and, more broadly, of respiratory pathogens.Significance StatementOur study utilized passively recorded cellular signaling data and epidemiological surveillance data to investigate the changes human mobility to a COVID-19 outbreak at an unprecedented within-city level and examine its relationship with the actual risk of infection. Our findings highlight the heterogeneous behavioral change of the Shanghai population to the 2022 SARS-CoV-2 Omicron BA.2 outbreak and its heterogenous effect on the SARS-CoV-2 spread, both spatially and demographically. The implications of our findings could be instrumental to inform spatially targeted interventions at the within-city scale to mitigate possible new surges of COVID-19 cases as well as fostering preparedness for future respiratory infections disease outbreaks.

We report a general, scalable, and convenient photochemical process for diversities of distal oxygenated nitriles from corresponding less-strained ketoxime esters allowing one-step introductions of ether and cyano groups, which avoids the utilization of toxic cyanide reagents. A wide range of ketoxime esters involving five-membered to eight-membered cycloketoxime esters and linear ketoxime esters participate smoothly under operately simple and mild conditions, affording structurally variable ring-opening products.

A copper-catalysed three-component reaction utilizing readily available feedstocks was investigated, providing an operationally simple and practical route to trifluoromethyl allenes under mild and environmentally friendly conditions.

Functional molecules bearing polychlorinated moieties usually play versatile roles in organic synthesis and biochemistry. A copper-catalyzed multicomponent polychloro-carboalkynylation of alkenes presents an efficient and operationally simple approach for the synthesis of β-polychlorinated alkynes. Mechanistic experiments were conducted demonstrating that an

We have developed a modular, convenient and practical copper-catalyzed platform for the preparation of alkene nitriles from corresponding cycloketoxime esters via radical-mediated C–C bond cleavage. A broad scope of cycloketoxime esters (4-membered to 8-membered) and some complex substrates derived from natural product derivatives performed well, affording corresponding ring opening products in the presence of copper salts. Moreover, the etherification, oxidation and alkynylation of cycloketoxime esters could also be achieved under variable copper-catalyzed conditions.

It is attractive to establish an efficient and practical platform affording functional compounds using readily available feedstocks as starting materials under mild conditions. We describe a direct copper-catalyzed fluorocarboalkynylation of the readily available alkynes with excellent regio- and stereoselectivity. A wide range of conjugated trifluoromethyl 1,3-enynes were obtained in good yields by this operationally simple strategy. The mechanistic experiments and DFT calculation revealed that a radical-mediated process was involved in the catalytic cycle.

Correction for ‘Copper-catalysed synthesis of trifluoromethyl allenes via fluoro-carboalkynylation of alkenes’ by Mengning Wang et al., Org. Chem. Front., 2022, 9, 1844–1849, https://doi.org/10.1039/D1QO01823J.

2020 was an unprecedented year, with rapid and drastic changes in human mobility due to the COVID-19 pandemic. To understand the variation in commuting patterns among the Chinese population across stable and unstable periods, we used nationwide mobility data from 318 million mobile phone users in China to examine the extreme fluctuations of population movements in 2020, ranging from the Lunar New Year travel season (chunyun), to the exceptional calm of COVID-19 lockdown, and then to the recovery period. We observed that cross-city movements, which increased substantially in chunyun and then dropped sharply during the lockdown, are primarily dependent on travel distance and the socio-economic development of cities. Following the Lunar New Year holiday, national mobility remained low until mid-February, and COVID-19 interventions delayed more than 72.89 million people returning to large cities. Mobility network analysis revealed clusters of highly connected cities, conforming to the social-economic division of urban agglomerations in China. While the mass migration back to large cities was delayed, smaller cities connected more densely to form new clusters. During the recovery period after travel restrictions were lifted, the netflows of over 55% city pairs reversed in direction compared to before the lockdown. These findings offer the most comprehensive picture of Chinese mobility at fine resolution across various scenarios in China and are of critical importance for decision making regarding future public-health-emergency response, transportation planning and regional economic development, among others., This article gives an overview of commuting patterns in China in 2020, offering the most comprehensive understanding on national mobility at fine resolution across various scenarios in China.

Polymorphic HLAs form the primary immune barrier to cell therapy. In addition, innate immune surveillance impacts cell engraftment, yet a strategy to control both, adaptive and innate immunity, is lacking. Here we employed multiplex genome editing to specifically ablate the expression of the highly polymorphic HLA-A/-B/-C and HLA class II in human pluripotent stem cells. Furthermore, to prevent innate immune rejection and further suppress adaptive immune responses, we expressed the immunomodulatory factors PD-L1, HLA-G, and the macrophage “don’t-eat me” signal CD47 from the AAVS1 safe harbor locus. Utilizing in vitro and in vivo immunoassays, we found that T cell responses were blunted. Moreover, NK cell killing and macrophage engulfment of our engineered cells were minimal. Our results describe an approach that effectively targets adaptive as well as innate immune responses and may therefore enable cell therapy on a broader scale.

Adult acute myeloid leukemia (AML) clinically is a disparate disease that requires intensive treatments ranging from chemotherapy alone to allogeneic hematopoietic cell transplantation (allo-HCT). Historically, cytogenetic analysis has been a useful prognostic tool to classify patients into favorable, intermediate, and unfavorable prognostic risk groups. However, the intermediate-risk group, consisting predominantly of cytogenetically normal AML (CN-AML), itself exhibits diverse clinical outcomes and requires further characterization to allow for more optimal treatment decision-making. The recent advances in clinical genomics have led to the recategorization of CN-AML into favorable or unfavorable subgroups. The relapsing nature of AML is thought to be due to clonal heterogeneity that includes founder or driver mutations present in the leukemic stem cell population. In this article, we summarize the clinical outcomes of relevant molecular mutations and their cooccurrences in CN-AML, includingNPM1,FLT3ITD,DNMT3A,NRAS,TET2,RUNX1,MLLPTD,ASXL1,BCOR,PHF6,CEBPAbiallelic,IDH1,IDH2R140, andIDH2R170, with an emphasis on their relevance to the leukemic stem cell compartment. We have reviewed the available literature and TCGA AML databases (2013) to highlight the potential role of stem cell regulating factor mutations on outcome within newly defined AML molecular subgroups.

Nacre has achieved an excellent combination of strength and toughness through its unique brick-and-mortar structure of layered aragonite platelets bonded with biopolymers. Mimicking nacre has been considered as a practical way for the development of high-performance structural composites. Over the past years, many techniques have been developed to fabricate multifunctional nacre-mimetic materials, including freeze casting, layer-by-layer assembly, vacuum filtration, 3D printing and so on. Among them, freeze casting, especially bidirectional freeze casting, as an environmentally friendly and scalable method, has attracted extensive attention recently. In this review, we begin with the introduction and discussion of various fabrication techniques comparing their advantages and disadvantages, focusing on the most recent advances of the bidirectional freeze casting technique. Then, we summarize representative examples of applying the bidirectional freeze casting technique to assemble various building blocks into multifunctional nacre-mimetic materials and their wide applications. At the end, we discuss the future direction of using bidirectional freeze casting to make nacre-mimetic materials.

Glioma is a complex disease with limited treatment options. Recent advances have identified isocitrate dehydrogenase (IDH) mutations in up to 80% lower grade gliomas (LGG) and in 76% secondary glioblastomas (GBM). IDH mutations are also seen in 10%-20% of acute myeloid leukemia (AML). In AML, it was determined that mutations of IDH and other genes involving epigenetic regulations are early events, emerging in the pre-leukemic stem cells (pre-LSCs) stage, whereas mutations in genes propagating oncogenic signal are late events in leukemia. IDH mutations are also early events in glioma, occurring before TP53 mutation, 1p/19q deletion, etc. Despite these advances in glioma research, studies into other molecular alterations have lagged considerably. In this study, we analyzed currently available databases. We identified EZH2, KMT2C, and CHD4 as important genes in glioma in addition to the known gene IDH1/2. We also showed that genomic alterations of PIK3CA, CDKN2A, CDK4, FIP1L1, or FUBP1 collaborate with IDH mutations to negatively affect patients' survival in LGG. In LGG patients with TP53 mutations or IDH1/2 mutations, additional genomic alterations of EZH2, KMC2C, and CHD4 individually or in combination were associated with a markedly decreased disease-free survival than patients without such alterations. Alterations of EZH2, KMT2C, and CHD4 at genetic level or protein level could perturb epigenetic program, leading to malignant transformation in glioma. By reviewing current literature on both AML and glioma and performing bioinformatics analysis on available datasets, we developed a hypothetical model on the tumorigenesis from premalignant stem cells to glioma.