Single-nucleus RNA sequencing and mRNA hybridization indicate key bud events and LcFT1 and LcTFL1-2 mRNA transportability during floral transition in litchi.

In flowering plants, floral induction signals intersect at the shoot apex to modulate meristem determinacy and growth form. Here, we report a single-nucleus RNA sequence analysis of litchi apical buds at different developmental stages. A total of 41 641 nuclei expressing 21 402 genes were analyzed, revealing 35 cell clusters corresponding to 12 broad populations. We identify genes associated with floral transition and propose a model that profiles the key events associated with litchi floral meristem identity by analyzing 567 identified floral meristem cells at single cell resolution. Interestingly, single-nucleus RNA-sequencing data indicated that all putative FT and TFL1 genes were not expressed in bud nuclei, but significant expression was detected in bud samples by RT-PCR. Based on the expression patterns and gene silencing results, we highlight the critical role of LcTFL1-2 in inhibiting flowering and propose that the LcFT1/LcTFL1-2 expression ratio may determine the success of floral transition. In addition, the transport of LcFT1 and LcTFL1-2 mRNA from the leaf to the shoot apical meristem is proposed based on in situ and dot-blot hybridization results. These findings allow a more comprehensive understanding of the molecular events during the litchi floral transition, as well as the identification of new regulators.

How Can Resource-Exhausted Cities Get Out of "The Valley of Death"? An Evaluation Index System and Obstacle Degree Analysis of Green Sustainable Development.

Resource-based cities are suffering from resource scarcity and environmental deterioration. Spirit, vitality and prosperity are disappearing and cities have moved towards "the valley of death" in terms of urban development. This typically appears in environments where it is difficult to maintain sustainable development. Based on empirical analysis, a qualitative analysis method for the selection of evaluation indicators, as well as a quantitative analysis method for index weighting and principal component extraction for constructing a three-level evaluation index system of green development for coal-resource-exhausted cities, was adopted. This study also discussed the life cycle at different development stages of resource-based cities, including mature resource-based and growing resource-based cities. We further argued that the obstacle degree can act as an evaluation basis and make recommendations accordingly to improve the green development of cities. Through star-standard divisions and statistical analysis, it can be explicated that the increase in green development in the first stage is greater than that in the later stage, which is more obvious in cities with lower stars. The results also show the evolution trend and stability coefficient. There is no end in sight for urban green development, and this study can provide a new perspective to relieve the declining trend and promote green sustainable development.

Comparison of different endometrial preparation protocols on frozen embryo transfer pregnancy outcome in patients with normal ovulation.

RESEARCH QUESTION: What is the effect of letrozole use in patients undergoing frozen embryo transfer (FET) with normal ovulation? Although the number of FETs is increasing, an optimal protocol for FET (particularly vitrified-warmed embryo transfer) is yet to be determined. The aim of this study was to evaluate letrozole use on patients with normal menstrual cycles compared with hormone replacement therapy (HRT) cycles and natural cycles. DESIGN: The study involved 2849 patients. Patients were divided into three groups: HRT cycle (n = 2115), letrozole cycle (n = 532) and natural cycle (n = 202). Inverse probability of treatment weighting aimed to equate each group according to measured baseline covariates to achieve a comparison with reduced selection bias and live birth rate as main pregnancy outcome was analysed. RESULTS: In the crude analysis, the letrozole group had a higher live birth rate compared with the HRT cycle (OR 1.18, 95% CI 1.06 to 1.33) and natural cycle (OR 1.24, 95% CI 1.11 to 1.41); after adjusting for confounding factors, live birth rate was consistently higher in the letrozole group. Moreover, the biochemical pregnancy, clinical pregnancy, ongoing pregnancy and full-term delivery rates were higher in the letrozole group. CONCLUSION: For infertile women with normal menstrual cycle undergoing FET, mildly stimulated cycles with letrozole present a relatively large advantage compared with HRT cycle and natural cycle, with higher live birth pregnancy, indicating that letrozole administration could improve pregnancy outcomes in this population.

Experiment and numerical investigation of inhalable particles and indoor environment with ventilation system.

After the outbreak of COVID-19, the indoor environment has become particularly important in closed spaces, being a common concern in environmental science and public health, and of great significance for the building environment. To improve the indoor air quality and control the spread of viruses, the analysis of inhalable particles in indoor environments is critical. In this research, we study standards focused on inhalable particles and indoor environmental quality, as well as analyzing the movement and diffusion of indoor particles. Based on our analysis, we conduct an experimental study to determine the distribution of indoor inhalable particles of different sizes before and after diffusion under the conditions of underfloor air distribution. Furthermore, the mathematical modeling method is adopted to simulate the indoor flow field, particle trajectories, and pollutant dispersion process. The k-ε two-equation model is applied as the turbulence model in the numerical simulation, while the Lagrangian discrete phase model is adopted to trace the motion of particles and analyze the distribution characteristics of indoor particles. The results demonstrate that fine particles (i.e., those with size less than 0.5 µm) have a significant impact on the indoor particle concentration, while coarse particles (i.e., with size above 2.5 µm) have a greater influence on the total mass concentration of indoor particles. Small-sized particles can easily follow the airflow and diffuse to upper parts of the room. Overall, the effects of indoor particles on indoor air quality, including the potential threat of aerosol transmission of respiratory infectious diseases, are non-negligible. Application of the presented research can contribute to improving the health-related aspects of the building environment.

Analysis of the spatio-temporal network of air pollution in the Yangtze River Delta urban agglomeration, China.

The complex correlation between regions caused by the externality of air pollution increases the difficulty of its governance. Therefore, analysis of the spatio-temporal network of air pollution (STN-AP) holds great significance for the cross-regional coordinated governance of air pollution. Although the spatio-temporal distribution of air pollution has been analyzed, the structural characteristics of the STN-AP still need to be clarified. The STN-AP in the Yangtze River Delta urban agglomeration (YRDUA) is constructed based on the improved gravity model and is visualized by UCINET with data from 2012 to 2019. Then, its overall-individual-clustering characteristics are analyzed through social network analysis (SNA) method. The results show that the STN-AP in the YRDUA was overall stable, and the correlation level gradually improved. The centrality of every individual city is different in the STN-AP, which reveals the different state of their interactive mechanism. The STN-AP could be subdivided into the receptive block, overflow block, bidirectional block and intermediary block. Shanghai, Suzhou, Hangzhou and Wuxi could be key cities with an all above degree centrality, betweenness centrality and closeness centrality and located in the overflow block of the STN-AP. This showed that these cities had a greater impact on the STN-AP and caused a more pronounced air pollution spillovers. The influencing factors of the spatial correlation of air pollution are further determined through the quadratic assignment procedure (QAP) method. Among all factors, geographical proximity has the strongest impact and deserves to be paid attention in order to prevent the cross-regional overflow of air pollution. Furthermore, several suggestions are proposed to promote coordinated governance of air pollution in the YRDUA.

Dietary fruit and vegetable intake, gut microbiota, and type 2 diabetes: results from two large human cohort studies.

BACKGROUND: Little is known about the inter-relationship among fruit and vegetable intake, gut microbiota and metabolites, and type 2 diabetes (T2D) in human prospective cohort study. The aim of the present study was to investigate the prospective association of fruit and vegetable intake with human gut microbiota and to examine the relationship between fruit and vegetable-related gut microbiota and their related metabolites with type 2 diabetes (T2D) risk. METHODS: This study included 1879 middle-age elderly Chinese adults from Guangzhou Nutrition and Health Study (GNHS). Baseline dietary information was collected using a validated food frequency questionnaire (2008-2013). Fecal samples were collected at follow-up (2015-2019) and analyzed for 16S rRNA sequencing and targeted fecal metabolomics. Blood samples were collected and analyzed for glucose, insulin, and glycated hemoglobin. We used multivariable linear regression and logistic regression models to investigate the prospective associations of fruit and vegetable intake with gut microbiota and the association of the identified gut microbiota (fruit/vegetable-microbiota index) and their related fecal metabolites with T2D risk, respectively. Replications were performed in an independent cohort involving 6626 participants. RESULTS: In the GNHS, dietary fruit intake, but not vegetable, was prospectively associated with gut microbiota diversity and composition. The fruit-microbiota index (FMI, created from 31 identified microbial features) was positively associated with fruit intake (p < 0.001) and inversely associated with T2D risk (odds ratio (OR) 0.83, 95%CI 0.71-0.97). The FMI-fruit association (p = 0.003) and the FMI-T2D association (OR 0.90, 95%CI 0.84-0.97) were both successfully replicated in the independent cohort. The FMI-positive associated metabolite sebacic acid was inversely associated with T2D risk (OR 0.67, 95%CI 0.51-0.86). The FMI-negative associated metabolites cholic acid (OR 1.35, 95%CI 1.13-1.62), 3-dehydrocholic acid (OR 1.30, 95%CI 1.09-1.54), oleylcarnitine (OR 1.77, 95%CI 1.45-2.20), linoleylcarnitine (OR 1.66, 95%CI 1.37-2.05), palmitoylcarnitine (OR 1.62, 95%CI 1.33-2.02), and 2-hydroglutaric acid (OR 1.47, 95%CI 1.25-1.72) were positively associated with T2D risk. CONCLUSIONS: Higher fruit intake-associated gut microbiota and metabolic alteration were associated with a lower risk of T2D, supporting the public dietary recommendation of adopting high fruit intake for the T2D prevention.

Highly Efficient Mesoporous Core-Shell Structured Ag@SiO2 Nanosphere as an Environmentally Friendly Catalyst for Hydrogenation of Nitrobenzene.

The size-uniformed mesoporous Ag@SiO2 nanospheres' catalysts were prepared in one-pot step via reducing AgNO3 by different types of aldehyde, which could control the size of Ag@SiO2 NPs and exhibit excellent catalytic activity for the hydrogenation of nitrobenzene. The results showed that the Ag core size, monitored by different aldehydes with different reducing abilities, together with the ideal monodisperse core-shell mesoporous structure, was quite important to affect its superior catalytic performances. Moreover, the stability of Ag fixed in the core during reaction for 6 h under 2.0 MPa, 140 °C made this type of Ag@SiO2 catalyst separable and environmentally friendly compared with those conventional homogeneous catalysts and metal NPs catalysts. The best catalyst with smaller Ag cores was prepared by strong reducing agents such as CH2O. The conversion of nitrobenzene can reach 99.9%, the selectivity was 100% and the catalyst maintained its activity after several cycles, and thus, it is a useful novel candidate for the production of aniline.

Mannose-Modified Multi-Walled Carbon Nanotubes as a Delivery Nanovector Optimizing the Antigen Presentation of Dendritic Cells.

Dendritic cells (DCs) based cancer immunotherapy is largely dependent on adequate antigen delivery and efficient induction of DCs maturation to produce sufficient antigen presentation and ultimately lead to substantial activation of tumor-specific CD8+ T cells. Carbon nanotubes (CNTs) have attracted great attention in biomedicine because of their unique physicochemical properties. In order to effectively deliver tumor antigens to DCs and trigger a strong anti-tumor immune response, herein, a specific DCs target delivery system was assembled by using multi-walled carbon nanotubes modified with mannose which can specifically bind to the mannose receptor on DCs membrane. Ovalbumin (OVA) as a model antigen, could be adsorbed on the surface of mannose modified multi-walled carbon nanotubes (Man-MWCNTs) with a large drug loading content. This nanotube-antigen complex showed low cytotoxicity to DCs and was efficiently engulfed by DCs to induce DCs maturation and cytokine release in vitro, indicating that it could be a potent antigen-adjuvant nanovector of efficient antigen delivery for therapeutic purpose.

MiR-483-3p regulates oxaliplatin resistance by targeting FAM171B in human colorectal cancer cells.

Oxaliplatin resistance limits the efficiency of treatment for colorectal cancer (CRC). Studies have shown that abnormal expression of microRNAs (miRNAs) were associated with tumorigenesis, cancer development and chemoresistance. The purpose of this study was to identify potential miRNAs related to oxaliplatin resistance in CRC cells. In this work, using small RNA sequencing (small RNA-Seq) and transcriptome sequencing (RNA-Seq), we found that down-regulated miR-483-3p was concurrent with up-regulated FAM171B in oxaliplatin-resistant colorectal cancer cell line HCT116/L as compared with its parental cell line HCT116. Transient transfection of miR-483-3p mimics markedly decreased the levels of FAM171B and restored oxaliplatin responsiveness of HCT116/L cells, and this alteration enhanced cell apoptosis and weakened cell migration. Whereas miR-483-3p inhibitor dramatically promoted the expression of FAM171B and enhanced oxaliplatin resistance of HCT116 cells by repressing cell apoptosis. Furthermore, knockdown of FAM171B in HCT116/L cells could also sensitize its reaction of the treatment with oxaliplatin, which was verified by the reduced cell migration. These findings demonstrate that FAM171B is a functional target of miR-483-3p in the regulation of oxaliplatin resistance in human CRC cells.

Dishevelled 1, a pivotal positive regulator of the Wnt signalling pathway, mediates 5-fluorouracil resistance in HepG2 cells.

Acquired resistance to 5-fluorouracil (5-FU) frequently occurs in patients with hepatocellular carcinoma (HCC), the underlying molecular mechanisms of which are poorly understood. The aim of this study was to identify candidate genes and associated signalling pathways that may play a role in developing drug resistance following repeated 5-FU treatments. In this work, we established 5-FU-resistant cells (HepG2/5-FU) using stepwise increasing concentrations of 5-FU in parental HepG2 cells. Using transcriptome sequencing, we found that the expressions of the Wnt signalling genes, including negative regulators (DKK1, DKK3, ZNRF3, RNF43 and APC2) and positive regulators (FZD10 and DVL1), were significantly downregulated and upregulated in HepG2/5-FU cells, respectively, resulting in increased Wnt signalling. Dishevelled-1 (DVL1) is an essential Wnt signalling pathway component that stabilizes ß-catenin and mediates the Wnt pathway. Silencing DVL1 using siDVL1 or other small molecular inhibitors in HepG2/5-FU cells could restore 5-FU responsiveness via reduced cell proliferation and migration, and increased apoptosis. Moreover, DVL1 was found to be upregulated in BEL-7402/5-FU cells when compared to the parental BEL-7402 cells. Collectively, our results provide the first clue towards understanding the contribution of DVL1-mediated acquired resistance to 5-FU in HepG2/5-FU cells, suggesting a promising therapeutic strategy for liver cancer resistant to 5-FU.

Concurrent Hypermethylation of SFRP2 and DKK2 Activates the Wnt/ß-Catenin Pathway and Is Associated with Poor Prognosis in Patients with Gastric Cancer.

Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of ß-catenin, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was considered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient's age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.

The allele frequency of CYP2A6*4 in four ethnic groups of China.

The CYP2A6*4 allele, characterized as the whole deletion of this gene, is closely associated with nicotine dependence, cancer susceptibility, and drug responsiveness. The frequency of this molecular variant differs across populations. Although genetic polymorphisms of CYP2A6*4 and its functional results have been reported in Chinese Han population, the allele frequency of CYP2A6*4 was largely unknown in other Chinese ethnic population. In this study, we investigated the allele frequency of CYP2A6*4 in four main ethnic groups of China based on our newly developed quantitative real-time PCR assay. The frequencies of the CYP2A6*4 allele were 7.9%, 15%, 0% and 2% in Han (N=120), Uighur (N=100), Bouyei (N=100) and Tibetan (N=100) (P<0.0001), respectively. This work greatly expanded our understanding of the distribution of CYP2A6*4 in Chinese population and provided more information of different ethnic population's smoking behavior and also in disease susceptibility and drug response.