With rapid urbanization in recent years, severe air pollution has emerged as a major issue for many regions of China, especially in some metropolises. A persistent pollution case during 6 December 2016–8 January 2017 was selected to investigate the relations between turbulent intermittency and frequent PM2.5 (particulate matters with diameter less than 2.5 μm) pollution events over the metropolitan region of Beijing, China. The accumulation of PM2.5 near the surface frequently occurred as a combined result of strong inversion layers, stagnant winds, high ambient humidity levels, and stable stratification during this case. Arbitrary-order Hilbert spectral analysis indicated that steep decreases in the PM2.5 concentration were simultaneous with the occurrence of intermittent turbulence and strong vertical mixing. A wind profiler observation revealed existence of low-level jets (LLJs) at the end of the polluted periods, suggesting that the upper-level turbulent mixing accompanied by the wind shear of LLJ was transported downward and enhanced the vertical mixing near the surface, which might have caused an abrupt reduction in PM2.5 and improvement in air conditions.
Abstract Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of the protein. This includes ZNF529 :p.K405X, which is associated with decreased low-density-lipoprotein (LDL) cholesterol (P = 1.3 × 10 −8 ) without being associated with liver enzymes or non-fasting blood glucose. Silencing of ZNF529 in human hepatoma cells results in upregulation of LDL receptor and increased LDL uptake in the cells. This suggests that inhibition of ZNF529 or its gene product should be prioritized as a novel candidate drug target for treating dyslipidemia and associated CVD.
Hydroquinone (HQ) is one of the major metabolites of benzene and can cause abnormal gene expression. It is a known carcinogen that alters cell cycle disruption and cell proliferation. However, its chemical mechanism remain a mystery. Circular RNAs (circRNAs) are a subtype of noncoding RNAs (ncRNAs) that play a variety of roles in biological processes. Hsa_circ_001944 expression was upregulated in 30 leukemia patients and HQ-induced malignant transformed TK6 cells. Hsa_circ_001944 silencing inhibited the growth of HQ-TK6 cells and halted the cell cycle. The silencing of hsa_circ_0001944 led to increased cell accumulation in G1 versus S phase, increased apoptosis in the sh1944 versus the shNC group, and increased levels of DNA damage (γ-H2AX), leading to cell cycle arrest. In summary, inhibition of hsa_circ_001944 restricted cell growth by inhibiting cell cycle arrest and induced growth of HQ-TK6 cells by modulating PARP1 expression. Hsa_circ_0001944 targeted HuR, which is a kind of RNA-binding protein, to control PARP1 expression via RNAinter, RBPmap, and RBPdb. Fluorescence in situ hybridization combined with immunofluorescent labeling and western blotting experiments showed that hsa_circ_001944 was able to dissociate HuR and PARP1 binding in HQ-TK6 cells, control PARP1 production, and ultimately alter the PARP1/H-Ras pathway.
Low-carbon management plays an important role in mitigating climate change and adapting to it. Localities should adopt differentiated low-carbon management policies according to the state of their environment. To help formulate specific and realistic low-carbon management policies, this paper took into account specific low-carbon management sectors. Likewise, it carefully considered the differences in various resource endowments and proposed a method for evaluating low-carbon management efficiency and potential. The method was applied to an empirical study from 2015 conducted on 1771 Chinese counties. Significant spatial heterogeneity was found during the research. The counties bordering central and Western China and the ones in the southeast coastal areas showed higher efficiency in the industrial sector. Southern and Northern China had higher efficiency in the housing and transportation sector, respectively. Moreover, counties in remote areas showed more potential in the industrial sector. Central China had higher potential in the housing sector, while counties bordering provinces had more potential in the transportation sector. Therefore, Chinese counties were divided into eight management zones where differentiated management strategies were identified to shape low-carbon management policies.
DNMT3B plays a crucial role in the generation of aberrant methylation during carcinogenesis. Polymorphisms in the DNMT3B gene may influence the DNA methylation enzymatic activity of DNMT3B, thereby modulating the susceptibility to AML. Thus, we investigated the association between SNPs in the DNMT3Bgene and their haplotypes with the risk of AML in the Chinese Han population. The DNMT3B genotype was determined by HRM in 317 de novo AML patients and 406 healthy control subjects matched for age and gender. Among the 5 SNPs investigated in this study, rs2424913 demonstrated no polymorphisms in the Chinese Han populations, rs1569686 and rs2424908 were significantly associated with AML risk. The GG genotype of rs1569686 was associated with increased AML risk (OR: 5.76; 95%CI: 2.60-12.73; P<0.01) compared with the TT genotype, and individuals with a G allele had a significantly increased risk (OR: 1.89; 95%CI: 1.41-2.52; P<0.01) for AML compared with those harboring a C allele, this polymorphism can predict the risk of AML in a minority of patients. While the CC genotype of rs2424908 appeared to reduce the AML risk (OR: 0.57; 95%CI: 0.36-0.91; P=0.01) compared with the TT genotype, individuals with a C allele were associated with a lower risk (OR: 0.79, 95%CI: 0.64-0.97, P=0.03) for developing AML compared with those harboring a T allele. The other 2 SNPs, rs6087990 and rs6119954, had no significant association with AML risk in the study population. The CGGT, CTAT, TGAT, and CGAT haplotypes of rs6087990, rs1569686, rs6119954, and rs2424908 appeared to significantly increase the AML risk, and the TTGC haplotype appeared to significantly reduce the risk. These results suggest that DNMT3B polymorphisms may contribute to the genetic susceptibility to AML; in particular, the G allele of rs1569686 serves as a risk factor for AML, whereas the C allele of rs2424908 represents a potential protective factor.
A new open-path methane analyzer (LI-7700) was adopted to measure methane (CH4) fluxes using eddy covariance method over irrigated rice fields in Yancheng, Jiangsu Province, China, throughout the 2016 growing season. A clear seasonal variation in the daily CH4 flux was observed. The CH4 flux started to increase 3 days after the fields were flooded. The peak CH4 flux was 0.37 gC m−2 d−1 and was reached during late vegetative stage (August 2). A distinct single-peak diurnal pattern of the CH4 flux was observed during the vegetative stages. The CH4 flux started to increase after sunrise and reached the peak at approximately 14:30 in the afternoon. Similar results were not observed during the reproductive and ripening stages. The diurnal patterns of soil temperature (Tsoil) and gross ecosystem photosynthesis (GEP) were consistent with that of the CH4 flux. The partial F tests showed that soil temperature and volumetric water content (VWC) were the most important factors controlling CH4 emissions from rice fields on seasonal timescale. The friction velocity (u*) was also found related to the CH4 emissions. Good agreements between the measured and modeled CH4 fluxes were obtained (R2 = 0.82, 0.86 and 0.86) using the models with different factors over the whole season. Including ambient pressure (P) and GEP in the model did not significantly improve the performance of the model. The best agreement between the measured and modeled CH4 fluxes was achieved by running the regression separately for each growth stage (R2 = 0.90). After the daily CH4 series was gap-filled, the total amount of CH4 emitted over the whole season was 19.20 ± 3.20 gC m−2.
Abstract Start-gain mutations can introduce novel start codons and generate novel coding sequences that may affect the function of genes. In this study, we systematically investigated the novel start codons that were either polymorphic or fixed in the human genomes. 829 polymorphic start-gain SNVs were identified in the human populations, and the novel start codons introduced by these SNVs have significantly higher activity in translation initiation. Some of these start-gain SNVs were reported to be associated with phenotypes and diseases in previous studies. By comparative genomic analysis, we found 26 human-specific start codons that were fixed after the divergence between the human and chimpanzee, and high-level translation initiation activity was observed on them. The negative selection signal was detected in the novel coding sequences introduced by these human-specific start codons, indicating the important function of these novel coding sequences.
We propose a simplified version of the inverse seesaw model, in which only two pairs of the gauge-singlet neutrinos are introduced, to interpret the observed neutrino mass hierarchy and lepton flavor mixing at or below the TeV scale. This minimal inverse seesaw scenario (MISS) is technically natural and experimentally testable. In particular, we show that the effective parameters describing the non-unitary neutrino mixing matrix are strongly correlated in the MISS, and thus, their upper bounds can be constrained by current experimental data in a more restrictive way. The Jarlskog invariants of non-unitary CP violation are calculated, and the discovery potential of such new CP-violating effects in the near detector of a neutrino factory is discussed.
Immunotherapy combined with chemotherapy has been demonstrated to be effective in early triple-negative breast cancer (TNBC). In this single-arm, phase II study with Simon's two-stage design, we investigated the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy in patients with early TNBC (NCT04213898). Eligible female patients aged 18 years or older with histologically confirmed treatment-naïve early TNBC were treated with camrelizumab (200 mg, on day 1), nab-paclitaxel (125 mg/m2, on days 1, 8, and 15), and epirubicin (75 mg/m2, on day 1) every three weeks for six cycles. The primary end point was the pathological complete response; secondary endpoints included safety, objective response rate, and long-term survival outcomes of event-free survival, disease-free survival, and distant disease-free survival. A total of 39 patients were enrolled between January 2020 and October 2021. Twenty-five patients achieved a pathological complete response (64.1%, 95%CI: 47.2, 78.8). The objective response rate was 89.7% (95%CI: 74.8, 96.7), including 35 patients with partial responses. Treatment-related adverse events of grade 3 or 4 occurred in 30 (76.9%) patients. In conclusion, the trial meets the prespecified endpoints showing promising efficacy and manageable safety of neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin chemotherapy in female patients with early TNBC. Long-term survival outcomes are still pending.
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