•The creative Fuzzy System is used to obtain the feature of WRFs’ outputs.•This system can reduce the NWP uncertainties and improve the forecasting accuracy.•The evolutionary algorithm, CS, can ...correct WRF’s forecasting values.•This novelty model outperforms other approaches in different wind farms.•The method is used for operational wind forecast within acceptable computations.
Accurate wind speed forecasting, which strongly influences the safe usage of wind resources, is still a critical issue and a huge challenge. At present, the single-valued deterministic NWP forecast is primarily adopted by wind farms; however, recent techniques cannot meet the actual needs of grid dispatch in many cases. This paper contributes to a new multi-step forecasting method for operational wind forecast, 96-steps of the next day, termed the CS-FS-WRF-E model, which is based on a Weather Research and Forecasting (WRF) ensemble forecast, a novel Fuzzy System, and a Cuckoo Search (CS) algorithm. First, the WRF ensemble, which considers three horizontal resolutions and four initial fields, using a 0.5° horizontal grid-spacing Global Forecast System (GFS) model output, is constructed as the basic forecasting results. Then, a novel fuzzy system, which can extract the features of these ensembles, is built under the concept of membership degrees. With the help of CS optimization, the final model is constructed using this evolutionary algorithm to adjust and correct the results obtained based on physical laws, yielding the best forecasting performance and outperforming individual ensemble members and all of the other models for comparison.
Triple-negative breast cancer (TNBC) is defined as a highly aggressive type of breast cancer which lacks specific biomarkers and drug targets. Damage-associated molecular pattern (DAMP)-induced ...immunogenic cell death (ICD) may influence the outcome of immunotherapy for TNBC patients. This study aims to develop a DAMPs gene signature to classify TNBC patients and to further predict their prognosis and immunotherapy outcome.
We identified the DAMPs-associated subtypes of 330 TNBCs using K-means analysis. Differences in immune status, genomic alterations, and predicted immunotherapy outcome were compared among each subtype.
A total of 330 TNBCs were divided into three subtypes according to DAMPs gene expression: the nuclear DAMPs subtype, featuring the upregulation of nuclear DAMPs; the inflammatory DAMPs subtype, characterized by the gene set enrichment of the adaptive immune system and cytokine signaling in the immune system; and the DAMPs-suppressed subtype, having the lowest level of ICD-associated DAMPs. Among them, the inflammatory subtype patients had the most favorable survival, while the DAMPs-suppressed subtype was associated with the worst prognosis. The DAMPs subtyping system was successfully validated in the TCGA cohort. Furthermore, we systemically revealed the genomic alterations among the three DAMPs subtypes. The inflammatory DAMPs subtype was predicted to have the highest response rate to immunotherapy, suggesting that the constructed DAMPs clustering had potential for immunotherapy efficacy prediction.
We established a novel ICD-associated DAMPs subtyping system in TNBC, and DAMPs expression might be a valuable biomarker for immunotherapy strategies. Our work could be helpful to the development of new immunomodulators and may contribute to the development of precision immunotherapy for TNBC.
The resistance of Helicobacter pylori (
H. pylori
) to antibiotics has been increasing worldwide and varies across different geographic areas and times. Limited studies reported the prevalence of ...antibiotic resistance and its related gene mutations in children in Chongqing, a city located in southwest China. We collected 112
H. pylori
strains isolated from gastric biopsies of 156 children at Children’s Hospital of Chongqing Medical University and calculated resistance rates of these strains to six antibiotics. The A2143G and A2142G mutations in 23S rRNA gene, which are related to clarithromycin resistance, and Asn87 and Asp91 mutations in gyrA gene, which are related to levofloxacin resistance, were investigated in 102 strains. The resistance rates to clarithromycin, metronidazole, and levofloxacin were 47.3% (53/112), 88.4% (99/112), and 18.8% (21/112), respectively. No resistance to amoxicillin, tetracycline, and furazolidone was observed. Dual and triple resistance percentages were 37.5% (42/112) and 10.7% (12/112), respectively. The detection rate of A2143G mutation in 23S rRNA gene was 83.3% (40/48). The detection rates of mutations of Asn87 and Asp91 in gyrA gene were 52.6% (10/19) and 36.8% (7/19), respectively.
Conclusion
: The prevalence of
H. pylori
resistance to clarithromycin, metronidazole, and levofloxacin was high in children in Chongqing, China. The A2143G mutation was detected in most clarithromycin-resistant strains, and Asn87 and Asp91 of gyrA mutation points were common in levofloxacin-resistant strains. In clinical practice, anti-
H. pylori
therapy should be individualized based on a susceptibility test.
What is Known:
• The resistance of H. pylori to antibiotics changes with the geographic areas and that in Asia the resistance rate is high.
• Mutation plays a vital role in antibiotics resistance of H. pylori.
What is New:
• High resistance rates to single and multiple antibiotics in children of Chongqing, a city located in southwest China, were observed.
• Molecular assays showed good conformance with susceptibility test results to direct antibiotic resistance of H. pylori.
In recent years, the sugarcane streak mosaic virus (SCSMV) has been the primary pathogen of sugarcane mosaic disease in southern China. In this study, the complete genome of a sugarcane mosaic sample ...(named YN-21) from Kaiyuan City, Yunnan Province, was amplified and sequenced. By comparing the amino acid sequences of YN-21 and 15 other SCSMV isolates from the NCBI database, the protease recognition site of SCSMV was determined. YN-21 had the highest nucleotide and amino acid identities of 97.66% and 99.30%, respectively, in comparison with the SCSMV isolate (JF488066). The P1 had the highest variability of 83.38–99.72% in the amino acid sequence, and 6K2 was the most conserved, with 97.92–100% amino acid sequence identity. A phylogenetic analysis of nucleotide and amino acid sequences clustered the 16 SCSMV isolates into two groups. All the Chinese isolates were clustered into the same group, and YN-21 was closely related to the Yunnan and Hainan isolates in China. Recombination analysis showed no major recombination sites in YN-21. Selective pressure analysis showed that the dN/dS values of 11 proteins of SCSMV were less than 1, all of which were undergoing negative selection. These results can provide practical guidance for monitoring SCSMV epidemics and genetics.
Objective To evaluate the effects of periodontal intervention on inflammatory cytokines, adiponectin, insulin resistance (IR), and metabolic control and to investigate the relationship between type 2 ...diabetes mellitus (T2DM) and moderately poor glycemic control and chronic periodontitis. Methods and Patients A total of 190 moderately poorly controlled (HbA1c between 7.5% and 9.5%) T2DM patients with periodontitis were randomly divided into two groups according to whether they underwent periodontal intervention: T2DM-NT and T2DM-T group. The levels of serum adiponectin, C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), lipid profile, glucose, insulin, homeostasis model of assessment - insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were measured at baseline and after 3 months. Results The levels of clinical periodontal variables, the probing depth, attachment loss, bleeding index, and plaque index were improved significantly in T2DM-T group after 3 months compared to T2DM-NT group (all p<0.01). After 3 months, the serum levels of hsCRP, TNF-α, IL-6, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS) and HOMA-IR index decreased, and adiponectin was significantly increased in T2DM-T group compared to those in the T2DM-NT group (p<0.05 or p<0.01). Conclusion Periodontal intervention can improve glycemic control, lipid profile and IR, reduce serum inflammatory cytokine levels and increase serum adiponectin levels in moderately poorly controlled T2DM patients.
We present an investigation of a coronal cavity observed above the western limb in the coronal red line Fe x 6374 using a telescope of Peking University and in the green line Fe xiv 5303 using a ...telescope of Yunnan Observatories, Chinese Academy of Sciences, during the total solar eclipse on 2017 August 21. A series of magnetic field models is constructed based on the magnetograms taken by the Helioseismic and Magnetic Imager on board the Solar Dynamics Observatory (SDO) one week before the eclipse. The model field lines are then compared with coronal structures seen in images taken by the Atmospheric Imaging Assembly on board SDO and in our coronal red line images. The best-fit model consists of a flux rope with a twist angle of 3.1π, which is consistent with the most probable value of the total twist angle of interplanetary flux ropes observed at 1 au. Linear polarization of the Fe xiii 10747 line calculated from this model shows a "lagomorphic" signature that is also observed by the Coronal Multichannel Polarimeter of the High Altitude Observatory. We also find a ring-shaped structure in the line-of-sight velocity of Fe xiii 10747 , which implies hot plasma flows along a helical magnetic field structure, in the cavity. These results suggest that the magnetic structure of the cavity is a highly twisted flux rope, which may erupt eventually. The temperature structure of the cavity has also been investigated using the intensity ratio of Fe xiii 10747 and Fe x 6374 .
Snow properties and their changes are crucial to better understanding of hydrological processes, soil thermal regimes, and surface energy balances. Reliable data and information on snow depth and ...snow water equivalent (SWE) are also crucial for water resource assessments and socio-economic development at local and regional scales. However, these data are extremely limited and unreliable in northern Xinjiang, China. This study thus aims to investigate spatial variations of snow depth, SWE, and snow density based on winter snowfield surveys during 2015 through 2017 in the Altai Mountains, northwestern China. The results indicated that snow depth (25–114 cm) and SWE (40–290 mm) were greater in the alpine Kanas-Hemu region, and shallow snow accumulated (9–42 cm for snow depth, 26–106 mm for SWE) on the piedmont sloping plain. While there was no remarkable regional difference in the distribution of snow density. Snow property distributions were strongly controlled by topography and vegetation. Elevation and latitude were the most important factors affecting snow depth and SWE, while snow density was strongly affected by longitude across the Altai Mountains in China. The influence of topography on snow property distributions was spatially heterogenous. Mean snow depth increased from 13.7 to 31.2 cm and SWE from 28.5 to 79.9 mm, respectively, with elevation increased from 400 to 1000 m a.s.l. on the piedmont sloping plain. Snow depth decreased to about 15.1 cm and SWE to about 28.5 mm from 1000 to 1800 m a.s.l., then again increased to about 98.1 cm and 271.7 mm on peaks (∼2000 m a.s.l.) in the alpine Kanas-Hemu. Leeward slopes were easier to accumulate snow cover, especially on north-, east-, and southeast-facing slopes. Canopy interception was also the cause of the difference in snow distribution. Snow depth, SWE, and snow density in forests were reduced by 8%–53%, 2%–67% and −4% to +48%, respectively, compared with surrounding open areas. Especially when snow depth was less than 40 cm, snow depth and SWE differences in forests were more exaggerated. This study provides a basic data set of spatial distributions and variations of snow depth, SWE and snow density in the Altai Mountains, which can be used as an input parameter in climate or hydrological models. These first-hand observations will help to better understand the relationship between snow, topography and climate in mountainous regions across northern China and other high-mountain Asian regions.
The effects of grape-tobacco intercropping patterns on populations of grape phylloxera, Daktulosphaira vitifoliae Fitch, as well as on the growth and development of the infested vines were evaluated ...in the field and the impact of an aqueous tobacco root extract on grape phylloxera was evaluated using a laboratory bioassay. The aqueous tobacco root extract exhibited biological activity against this pest. The egg mortality, nymph mortality, development period, life span and female fecundity were significantly affected. In the field trial, grape phylloxera populations were clearly lower as compared to the monoculture pattern. However, the rates of newly developed roots and newly infested grape roots were significantly higher and lower, in intercropping patterns than in the vine monoculture, respectively. The grape phylloxera population number on the grape roots decreased each year, and the vine trees gradually renewed upon continuous intercropping with tobacco over three years. These results confirmed that intercropping grapes with tobacco can effectively control grape phylloxera in an infested vineyard. The results also indicated that additional crops could be intercropped with grapes and are effective against grape phylloxera, which should be explored as an integrated approach for controlling the pest.
Polycomb repressive complex 1 (PRC1) is an essential epigenetic regulator that mainly controls histone H2A Lys119 mono‐ubiquitination (H2AK119ub). B cell‐specific Moloney murine leukemia virus ...Integration site 1 (BMI1) and really interesting new gene 1B (RING1B) are PRC1 core components and play critical roles in the development of various cancers. However, therapeutic agents targeting PRC1 are very limited. In this study, MS147, the first degrader of PRC1 core components, BMI1 and RING1B, is discovered via a novel protein complex degradation strategy that utilizes the target protein's interacting partner protein (embryonic ectoderm development (EED)). MS147, which comprises an EED small‐molecule binder linked to a ligand of the E3 ligase von Hippel‐Lindau (VHL), degrades BMI1/RING1B in an EED‐, VHL‐, ubiquitination‐, and time‐dependent manner. MS147 preferentially degrades BMI1/RING1B over polycomb repressive complex 2 (PRC2) core components. Consequently, MS147 effectively reduces H2AK119ub, but not histone H3 Lys27 tri‐methylation (H3K27me3), which is catalyzed by PRC2. Furthermore, MS147 effectively inhibits the proliferation of cancer cell lines that are insensitive to PRC2 inhibitors/degraders. Overall, this study provides a novel BMI1/RING1B degrader, which is a useful chemical tool to further investigate the roles of PRC1 in cancer, and a novel protein complex degradation strategy, which can potentially expand the degradable human proteome.
The first degrader of BMI1 and RING1B is achieved via a novel protein complex degrader strategy, which utilizes an EED small‐molecule binder linked to a ligand of the E3 ligase von Hippel‐Lindau to preferentially degrade PRC1 components, BMI1 and RING1B, over EED, by hijacking the ubiquitin‐proteasome system.
Unbound plasma concentrations may not reflect those in target tissues, and there is a need for methods to predict tissue partitioning. Here, we investigate the unbound liver partitioning (Kpu,u) of ...rosuvastatin, a substrate of hepatic organic anion transporting peptides, in cynomolgus monkeys and compare it with that determined using hepatocytes in vitro. Rosuvastatin (3 mg/kg) was administered orally to monkeys and plasma and liver (by ultrasound-guided biopsy) collected over time. Uptake into monkey hepatocytes was evaluated up to steady state. Binding in monkey plasma, liver, and hepatocytes was determined using equilibrium dialysis. Mean in vivo Kpu,u was 118 after correcting total liver partitioning by plasma and liver binding. In vitro uptake data were analyzed by compartmental modeling to determine active uptake clearance, passive diffusion, the intracellular unbound fraction, and Kpu,u. In vitro Kpu,u underpredicted that in vivo, resulting in the need for an empirical in vitro to in vivo scaling factor of 10. Adjusting model parameters using hypothetical scaling factors for transporter expression and surface area or assuming no effect of protein binding on active transport increased partitioning values by 1.1-, 6-, and 9-fold, respectively. In conclusion, in vivo rosuvastatin unbound liver partitioning in monkeys was underpredicted using hepatocytes in vitro. Modeling approaches that allow integrating corrections from passive diffusion or protein binding on active uptake could improve the estimation of in vivo intracellular partitioning of this organic anion transporting peptide substrate. A similar assessment of other active hepatic transport mechanisms could confirm and determine the extent to which limited accumulation in isolated hepatocytes needs to be considered in drug development.
PDF
