Avermectins are major antiparasitic agents used commercially in animal health, agriculture and human infections. To improve the fermentation efficiency of avermectins, for the first time a plasma jet ...generated by a novel atmospheric pressure glow discharge (APGD) was employed to generate mutations in Streptomyces avermitilis. The APGD plasma jet, driven by a radio frequency (RF) power supply with water-cooled and bare-metallic electrodes, was used as a new mutation method to treat the spores of S. avermitilis. The plasma jet yielded high total (over 30%) and positive (about 21%) mutation rates on S. avermitilis, and a mutated strain, designated as G1-1 with high productivity of avermectin B1a and genetic stability, was obtained. Because of the low jet temperature, the high concentrations of the chemically reactive species and the flexibility of its operation, the RF APGD plasma jet has a strong mutagenic effect on S. avermitilis. This is a proof-of-concept study for the use of an RF APGD plasma jet for inducing mutations in microbes. We have shown that the RF APGD plasma jet could be developed as a promising and convenient mutation tool for the fermentation industry and for use in biotechnology research.
Summary
Chicken infectious anaemia (CIA) is a disease with a highly economic impact in the poultry industry. The infected chickens are characterized by aplastic anaemia and extreme immunosuppression, ...followed by the increased susceptibility to secondary infectious pathogens and suboptimal immune responses for vaccination. Commercially available CIA vaccines are routinely used in the breeders in Taiwan to protect their progeny with maternal‐derived antibodies. However, CIA cases still occur in the field and little is known about the genetic characteristics of Taiwanese chicken anaemia viruses (CAVs). In this study, CAV DNA was detected in 72 of 137 flocks collected during 2010–2015. Among the PCR‐positive samples, the coding regions of 51 CAVs were sequenced. Phylogenetic analysis of the VP1 gene revealed that, although most of Taiwanese CAVs belonged to genotypes II and III, some isolates were clustered into a novel genotype (genotype IV). Moreover, a Taiwanese isolate in this novel genotype IV appeared to be derived from a recombination event between genotypes II and III viruses. Five Taiwanese CAV isolates were highly similar to the vaccine strains, 26P4 or Del‐Ros. Taken together, these results indicate that the sequences of CAVs in Taiwan are variable, and inter‐genotypic recombination had occurred between viruses of different genotypes. Moreover, vaccine‐like strains might induce clinical signs of CIA in chickens. Our findings could be useful for understanding the evolution of CAVs and development of a better control strategy for CIA.
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.
An overview of Sun–Sky Radiometer Observation Network (SONET) measurements in China is presented. Based on observations at 16 distributed SONET sites in China, atmospheric aerosol parameters are ...acquired via standardization processes of operational measurement, maintenance, calibration, inversion, and quality control implemented since 2010. A climatology study is performed focusing on total columnar atmospheric aerosol characteristics, including optical (aerosol optical depth, ÅngstrÖm exponent, fine-mode fraction, single-scattering albedo), physical (volume particle size distribution), chemical composition (black carbon; brown carbon; fine-mode scattering component, coarse-mode component; and aerosol water), and radiative properties (aerosol radiative forcing and efficiency). Data analyses show that aerosol optical depth is low in the west but high in the east of China. Aerosol composition also shows significant spatial and temporal variations, leading to noticeable diversities in optical and physical property patterns. In west and north China, aerosols are generally affected by dust particles, while monsoon climate and human activities impose remarkable influences on aerosols in east and south China. Aerosols in China exhibit strong light-scattering capability and result in significant radiative cooling effects.
Hypoxia inducible factor 2α (HIF-2α) is critical for primordial germ cell (PGC) survival as knockout of HIF-2α (HIF-2α−/−) decreases both expression of Oct-4 and PGC number in genital ridge. Hypoxia ...is known to stabilize HIF-2α protein from proteasomal degradation. However, little is known about the hypoxia-associated endocrinal signaling in HIF-2α expression. The current work demonstrates a role for an endocrine insulin-like growth factor-I receptor (IGF-IR)-PI3K/Akt-mTOR-HIF-2α regulatory loop in the proliferation and Oct-4 maintenance of PGC-like alkaline phosphatase positive mouse germline stem cells (AP+GSCs). We found that hypoxia greatly increased the cell proliferation and the levels of nuclear Oct-4/HIF-2α protein of AP+GSCs. The hypoxic-AP+GSCs presented stronger stemness ability for germ cell differentiation than normoxic, with expressions of c-KIT (differentiation germ cell marker), VASA (differentiation germ cell marker) and SCP3 (meiotic marker) using a renal capsule transplantation assay. Meanwhile, hypoxia significantly increased the expression levels of secreted-IGF-I and IGF-IR. The IGF-I dose dependently increased the HIF-2α expression levels in AP+GSCs; and, the inhibition of IGF-IR by RNA interference (shIGF-IR) or LY294002 (PI3K inhibitor)/Rapamycin (mTOR inhibitor) effectively suppressed the IGF-I- and/or hypoxia-induced HIF-2α and Oct-4 expression, suggesting that the IGF-IR and its downstream Akt/mTOR signaling are involved in the IGF-I/hypoxia effects. Additionally, knockdown of HIF-2α dramatically suppressed Oct-4 and IGF-IR protein levels in AP+GSC cells. In conclusion, the present study demonstrates a regulatory loop of IGF-IR-PI3K/Akt-mTOR-HIF-2α in proliferation and Oct-4 maintenance of PGC-like AP+GSCs under hypoxia. This finding provides insights into the niche endocrinology underlying early germ cell development.
Abstract We present the first catalog of very-high-energy and ultra-high-energy gamma-ray sources detected by the Large High Altitude Air Shower Observatory. The catalog was compiled using 508 days ...of data collected by the Water Cherenkov Detector Array from 2021 March to 2022 September and 933 days of data recorded by the Kilometer Squared Array from 2020 January to 2022 September. This catalog represents the main result from the most sensitive large coverage gamma-ray survey of the sky above 1 TeV, covering decl. from −20° to 80°. In total, the catalog contains 90 sources with an extended size smaller than 2° and a significance of detection at >5 σ . Based on our source association criteria, 32 new TeV sources are proposed in this study. Among the 90 sources, 43 sources are detected with ultra-high energy ( E > 100 TeV) emission at >4 σ significance level. We provide the position, extension, and spectral characteristics of all the sources in this catalog.
The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray ...observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9} GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.
Intervertebral disc degeneration usually starts from the inner nucleus pulposus (NP). The majority of previous NP-related studies assessed the outcome by the expression of chondrogenic markers since ...NP cells are chondrocyte like. However, NP cells are unique from chondrocytes and such assessments may be inappropriate. Very recently, several investigators published their findings about the transcriptional differences between NP cells and other related cell types on a genomic scale. In this review we discuss these recent findings and summarize the molecules that may be utilized as NP-specific markers to distinguish normal NP cells from several cell types and as markers that indicate its degeneration. We will revisit markers that distinguish NP cells from the outer surrounding annulus fibrosus (AF) cells and articular chondrocytes so as to facilitate authentic NP cell engineering from stem cells. Our review indicated that N-cadherin and keratin 19 have the potential to serve as common NP markers, as they distinguish healthy NP cells from AF cells, articular cartilage cells and degenerated NP cells.
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