A Nationwide Nitrogen Deposition Monitoring Network (NNDMN) containing 43 monitoring sites was established in China to measure gaseous NH3, NO2, and HNO3 and particulate NH4+ and NO3− in air and/or ...precipitation from 2010 to 2014. Wet/bulk deposition fluxes of Nr species were collected by precipitation gauge method and measured by continuous-flow analyzer; dry deposition fluxes were estimated using airborne concentration measurements and inferential models. Our observations reveal large spatial variations of atmospheric Nr concentrations and dry and wet/bulk Nr deposition. On a national basis, the annual average concentrations (1.3–47.0 μg N m−3) and dry plus wet/bulk deposition fluxes (2.9–83.3 kg N ha−1 yr−1) of inorganic Nr species are ranked by land use as urban > rural > background sites and by regions as north China > southeast China > southwest China > northeast China > northwest China > Tibetan Plateau, reflecting the impact of anthropogenic Nr emission. Average dry and wet/bulk N deposition fluxes were 20.6 ± 11.2 (mean ± standard deviation) and 19.3 ± 9.2 kg N ha−1 yr−1 across China, with reduced N deposition dominating both dry and wet/bulk deposition. Our results suggest atmospheric dry N deposition is equally important to wet/bulk N deposition at the national scale. Therefore, both deposition forms should be included when considering the impacts of N deposition on environment and ecosystem health.
We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China ...Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.
MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid ...leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French-American-British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1. The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy.
We present results on light weakly interacting massive particle (WIMP) searches with annual modulation (AM) analysis on data from a 1-kg mass p-type point-contact germanium detector of the CDEX-1B ...experiment at the China Jinping Underground Laboratory. Datasets with a total live time of 3.2 yr within a 4.2-yr span are analyzed with analysis threshold of 250 eVee. Limits on WIMP-nucleus (χ-N) spin-independent cross sections as function of WIMP mass (m_{χ}) at 90% confidence level (C.L.) are derived using the dark matter halo model. Within the context of the standard halo model, the 90% C.L. allowed regions implied by the DAMA/LIBRA and CoGeNT AM-based analysis are excluded at >99.99% and 98% C.L., respectively. These results correspond to the best sensitivity at m_{χ}<6 GeV/c^{2} among WIMP AM measurements to date.
Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy ...workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses.
Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany.
Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells.
This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.
Since December 2019, the novel coronavirus disease 2019 (COVID-19) that emerged in Wuhan city has spread rapidly around the world. The risk for poor outcome dramatically increases once a patient ...progresses to the severe or critical stage. The present study aims to investigate the risk factors for disease progression in individuals with mild to moderate COVID-19.
We conducted a cohort study that included 1007 individuals with mild to moderate COVID-19 from three hospitals in Wuhan. Clinical characteristics and baseline laboratory findings were collected. Patients were followed up for 28 days for observation of disease progression. The end point was the progression to a more severe disease stage.
During a follow up of 28 days, 720 patients (71.50%) had recovered or were symptomatically stable, 222 patients (22.05%) had progressed to severe disease, 22 patients (2.18%) had progressed to the critically ill stage and 43 patients (4.27%) had died. Multivariate Cox proportional hazards models identified that increased age (hazard ratio (HR) 2.56, 95% CI 1.97–3.33), male sex (HR 1.79, 95% CI 1.41–2.28), presence of hypertension (HR 1.44, 95% CI 1.11–1.88), diabetes (HR 1.82, 95% CI 1.35–2.44), chronic obstructive pulmonary disease (HR 2.01, 95% CI 1.38–2.93) and coronary artery disease (HR 1.83, 95% CI 1.26–2.66) were risk factors for disease progression. History of smoking was protective against disease progression (HR 0.56, 95% CI 0.34–0.91). Elevated procalcitonin (HR 1.72, 95% CI 1.02–2.90), urea nitrogen (HR 1.72, 95% CI 1.21–2.43), α-hydroxybutyrate dehydrogenase (HR 3.02, 95% CI 1.26–7.21) and D-dimer (HR 2.01, 95% CI 1.12–3.58) at baseline were also associated with risk for disease progression.
This study identified a panel of risk factors for disease progression in individuals with mild to moderate COVID-19.
To verify whether the concentrations and integrity index of circulating cell-free DNA (ccf-DNA) in serum may be clinically useful for the diagnosis and progression monitoring of colorectal cancer ...(CRC) patients.
Serum samples were collected from 104 with primary CRC, 85 with operated CRC, 16 with recurrent/metastatic CRC, 63 patients with intestinal polyps and 110 normal controls. Long (247 bp) and short (115 bp) DNA fragments in serum were detected by real-time quantitative PCR by amplifying the ALU repeats (ALU-qPCR). Serum carcinoembryonic antigen (CEA) level was detected by ARCHITECT assay.
The median absolute serum ALU115 and ALU247/115 in primary CRC group was significantly higher than those in intestinal polyp and normal control groups (both P<0.0001), in recurrent/metastatic CRC was significantly higher compared with primary CRC (P=0.0021, P=0.0018) or operated CRC (P<0.0001, respectively) and during follow-up, ALU115 and ALU247/115 were increased before surgery and decreased significantly after surgery.
Combined detection of ALU115, ALU247/115 and CEA could improve the diagnostic efficiency for CRC. Serum DNA concentrations and integrity index may be valuable in early complementary diagnosis and monitoring of progression and prognosis of CRC.
The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This ...work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2
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years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.
Aims
Ansamycins are a family of macrolactams that are synthesized by type I polyketide synthase (PKS) using 3‐amino‐5‐hydroxybenzoic acid (AHBA) as the starter unit. Most members of the family have ...strong antimicrobial, antifungal, anticancer and/or antiviral activities. We aimed to discover new ansamycins and/or other AHBA‐containing natural products from actinobacteria.
Methods and Results
Through PCR screening of AHBA synthase gene, we identified 26 AHBA synthase gene–positive strains from 206 plant‐associated actinomycetes (five positives) and 688 marine‐derived actinomycetes (21 positives), representing a positive ratio of 2·4–3·1%. Twenty‐five ansamycins, including eight new compounds, were isolated from six AHBA synthase gene–positive strains through TLC‐guided fractionations followed by repeated column chromatography. To gain information about those potential ansamycin gene clusters whose products were unknown, seven strains with phylogenetically divergent AHBA synthase genes were subjected to fosmid library construction. Of the seven gene clusters we obtained, three show characteristics for typical ansamycin gene clusters, and other four, from Micromonospora spp., appear to lack the amide synthase gene, which is unusual for ansamycin biosynthesis. The gene composition of these four gene clusters suggests that they are involved in the biosynthesis of a new family of hybrid PK‐NRP compounds containing AHBA substructure.
Conclusions
PCR screening of AHBA synthase is an efficient approach to discover novel ansamycins and other AHBA‐containing natural products.
Significance and Impact of the Study
This work demonstrates that the AHBA‐based screening method is a useful approach for discovering novel ansamycins and other AHBA‐containing natural products from new microbial resources.
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