Machine-assisted pathological recognition has been focused on supervised learning (SL) that suffers from a significant annotation bottleneck. We propose a semi-supervised learning (SSL) method based ...on the mean teacher architecture using 13,111 whole slide images of colorectal cancer from 8803 subjects from 13 independent centers. SSL (~3150 labeled, ~40,950 unlabeled; ~6300 labeled, ~37,800 unlabeled patches) performs significantly better than the SL. No significant difference is found between SSL (~6300 labeled, ~37,800 unlabeled) and SL (~44,100 labeled) at patch-level diagnoses (area under the curve (AUC): 0.980 ± 0.014 vs. 0.987 ± 0.008, P value = 0.134) and patient-level diagnoses (AUC: 0.974 ± 0.013 vs. 0.980 ± 0.010, P value = 0.117), which is close to human pathologists (average AUC: 0.969). The evaluation on 15,000 lung and 294,912 lymph node images also confirm SSL can achieve similar performance as that of SL with massive annotations. SSL dramatically reduces the annotations, which has great potential to effectively build expert-level pathological artificial intelligence platforms in practice.
Background and Aims
No effective treatments are available for liver fibrosis. Angiogenesis is deeply involved in liver fibrogenesis. However, current controversial results suggest it is difficult to ...treat liver fibrosis through vascular targeting. There are three different microvessels in liver: portal vessels, liver sinusoids, and central vessels. The changes and roles for each of the three different vessels during liver fibrogenesis are unclear. We propose that they play different roles during liver fibrogenesis, and a single vascular endothelial cell (EC) regulator is not enough to fully regulate these three vessels to treat liver fibrosis. Therefore, a combined regulation of multiple different EC regulatory signaling pathway may provide new strategies for the liver fibrosis therapy. Herein, we present a proof‐of‐concept strategy by combining the regulation of leukocyte cell‐derived chemotaxin 2 (LECT2)/tyrosine kinase with immunoglobulin‐like and epidermal growth factor–like domains 1 signaling with that of vascular endothelial growth factor (VEGF)/recombinant VEGF (rVEGF) signaling.
Approach and Results
The CCl4‐induced mouse liver fibrosis model and NASH model were both used. During fibrogenesis, vascular changes occurred at very early stage, and different liver vessels showed different changes and played different roles: decreased portal vessels, increased sinusoid capillarization and the increased central vessels the increase of portal vessels alleviates liver fibrosis, the increase of central vessels aggravates liver fibrosis, and the increase of sinusoid capillarization aggravates liver fibrosis. The combinational treatment of adeno‐associated viral vector serotype 9 (AAV9)–LECT2–short hairpin RNA (shRNA) and rVEGF showed improved therapeutic effects, but it led to serious side effects. The combination of AAV9‐LECT2‐shRNA and bevacizumab showed both improved therapeutic effects and decreased side effects.
Conclusions
Liver vascular changes occurred at very early stage of fibrogenesis. Different vessels play different roles in liver fibrosis. The combinational treatment of AAV9‐LECT2‐shRNA and bevacizumab could significantly improve the therapeutic effects on liver fibrosis.
Pyrometallurgy technique is usually applied as a pretreatment to enhance the leaching efficiencies in the hydrometallurgy process for recovering valuable metals from spent lithium‐ion batteries. ...However, traditional pyrometallurgy processes are energy and time consuming. Here, we report a carbothermal shock (CTS) method for reducing LiNi0.3Co0.2Mn0.5O2 (NCM325) cathode materials with uniform temperature distribution, high heating and cooling rates, high temperatures, and ultrafast reaction times. Li can be selectively leached through water leaching after CTS process with an efficiency of >90 %. Ni, Co, and Mn are recovered by dilute acid leaching with efficiencies >98 %. The CTS reduction strategy is feasible for various spent cathode materials, including NCM111, NCM523, NCM622, NCM811, LiCoO2, and LiMn2O4. The CTS process, with its low energy consumption and potential scale application, provides an efficient and environmentally friendly way for recovering spent lithium‐ion batteries.
Carbothermal shock (CTS) method with high heating and cooling rates, high temperatures (up to ≈2200 °C), and ultrafast reaction times of ≈20 s is utilized for recycling spent cathode materials. Li can be selectively leached through water leaching with an efficiency of >90 %. Ni, Co, and Mn are recovered by dilute acid leaching with efficiencies >98 %.
•LTM, industrial structure optimization and green TFP are integrated into a unified framework.•LTM, industrial structure rationalization and optimization all can improve green TFP, while their ...interactions would inhibit it in China.•There exist regional differences of the impact of LTM and industrial structure on green TFP across the regions in China.
Market-oriented allocation of land resources is one of the main economic reforms in China. However, the influence of land transfer marketization (LTM) on green total factor productivity (green TFP) and its mechanisms remain unknown. Based on panel data of 30 provincial administrative regions in China from 2004 to 2016, this study attempts to establish mechanism among LTM, industrial structure and green TFP, which is measured by the Slack Based Measure DEA (SBM-DEA) model containing undesirable output, and empirically estimates the impact of LTM, the rationalization and optimization of industrial structure and their interactions on green TFP further. The results show that: 1) LTM has a significant promoting effect on the improvement of green TFP in China, and the effect is also significant in the eastern, central and western regions as well, indicating that the application of land transfer policy to regulate regional economic development is widespread in China. 2) The rationalization of industrial structure has significantly promoted the development of green TFP in China, as well as at the regional levels, and the effect decreases from the western region to the central and eastern regions. The optimization of industrial structure also has a promoting effect on green TFP in China and all the regions, but the regional differences of the effect are contrary to that of the rationalization of industrial structure, with a decreasing trend from the eastern region to the central and western regions. 3) The interaction between LTM and the rationalization of industrial structure has significantly inhibited the improvement of green TFP in China, and the regional variations of the restraining effect are higher in the western region, followed by the central and eastern regions. The interaction between LTM and the optimization of industrial structure also has a negative effect on green TFP in China, and the regional variations of the effect showing the decreasing trend from the eastern region to the western and central regions. Therefore, China should continue to adhere to the market-oriented urban land transfer system reform, actively play the role of the government in the industrial upgrading and industrial transfer, and formulate a differentiated land transfer system and industrial development policies based on the economic development and industrial characteristics of various regions, so as to achieve the sustainable development of China’s economy and society.
The cereal endosperm is a major factor determining seed size and shape. However, the molecular mechanisms of endosperm development are not fully understood. Long noncoding RNAs (lncRNAs) function in ...various biological processes. Here we show a lncRNA, MISSEN, that plays an essential role in early endosperm development in rice (Oryza sativa). MISSEN is a parent-of-origin lncRNA expressed in endosperm, and negatively regulates endosperm development, leading to a prominent dent and bulge in the seed. Mechanistically, MISSEN functions through hijacking a helicase family protein (HeFP) to regulate tubulin function during endosperm nucleus division and endosperm cellularization, resulting in abnormal cytoskeletal polymerization. Finally, we revealed that the expression of MISSEN is inhibited by histone H3 lysine 27 trimethylation (H3K27me3) modification after pollination. Therefore, MISSEN is the first lncRNA identified as a regulator in endosperm development, highlighting the potential applications in rice breeding.
With advances in next-generation sequencing technologies, numerous novel transcripts in a large number of organisms have been identified. With the goal of fast, accurate assessment of the coding ...ability of RNA transcripts, we upgraded the coding potential calculator CPC1 to CPC2. CPC2 runs ∼1000 times faster than CPC1 and exhibits superior accuracy compared with CPC1, especially for long non-coding transcripts. Moreover, the model of CPC2 is species-neutral, making it feasible for ever-growing non-model organism transcriptomes. A mobile-friendly web server, as well as a downloadable standalone package, is freely available at http://cpc2.cbi.pku.edu.cn.
Melatonin (N‐acetyl‐5‐methoxytryptamine) plays important roles in plant defences against a variety of biotic and abiotic stresses, including UV‐B stress. Molecular mechanisms underlying functions of ...melatonin in plant UV‐B responses are poorly understood. Here, we show that melatonin effect on molecular signalling pathways, physiological changes and UV‐B stress resistance in Arabidopsis. Both exogenous and endogenous melatonin affected expression of UV‐B signal transduction pathway genes. Experiments using UV‐B signalling component mutants cop1‐4 and hy5‐215 revealed that melatonin not only acts as an antioxidant to promote UV‐B stress resistance, but also regulates expression of several key components of UV‐B signalling pathway, including ubiquitin‐degrading enzyme (COP1), transcription factors (HY5, HYH) and RUP1/2. Our findings indicate that melatonin delays and subsequently enhances expression of COP1, HY5, HYH and RUP1/2, which act as central effectors in UV‐B signalling pathway, thus regulating their effects on antioxidant systems to protect the plant from UV‐B stress.
Several studies have demonstrated that melatonin plays a role in UV‐B responses, however, the molecular mechanism whereby melatonin affects the UV‐B pathway was not clear. This study examined the function of melatonin in molecular signaling pathways, physiological changes, and UV‐B stress resistance under UV‐B radiation in Arabidopsis. Exogenous melatonin treatment experiment indicated that melatonin could enhance the transcriptional level of genes on UV‐B signaling pathway and ameliorate ROS damage caused by UV‐B stress. This result was verified in SNAT overexpressing lines and knock‐down mutant.
Methamphetamine use disorder (MAUD) can substantially jeopardize public security due to its high‐risk social psychology and behaviour. Given that the dopamine reward system is intimately correlated ...with MAUD, we investigated the association of single nucleotide polymorphisms (SNPs), as well as methylation status of dopamine receptor type 4 (DRD4), catechol‐O‐methyltransferase (COMT) genes, and paranoid and motor‐impulsive symptoms in MAUD patients. A total of 189 MAUD patients participated in our study. Peripheral blood samples were used to detect 3 SNPs and 35 CpG units of methylation in the DRD4 gene promoter region and 5 SNPs and 39 CpG units in the COMT gene. MAUD patients with the DRD4 rs1800955 C allele have a lower percentage of paranoid symptoms than those with the rs1800955 TT allele. Individuals with paranoid symptoms exhibited a reduced methylation degree at a particular DRD4 CpG2.3 unit. The interaction of the DRD4 rs1800955 C allele and the reduced DRD4CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Meanwhile, those with the COMT rs4818 CC allele had lower motor‐impulsivity scores in MAUD patients but greater COMT methylation levels in the promoter region and methylation degree at the COMT CpG 51.52 unit. Therefore, based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor‐impulsive scores. Our preliminary results provide a clue that the combination of SNP genotype and methylation status of the DRD4 and COMT genes serve as biological indicators for the prevalence of relatively high‐risk psychotic symptoms in MAUD patients.
The interaction of the DRD4 rs1800955 C allele and the reduced DRD4 CpG2.3 methylation degree were associated with a lower occurrence of paranoid symptoms. Based only on the COMT rs4818 CC polymorphism, there was a negative correlation between COMT methylation and motor‐impulsive scores. The combination of SNP genotype and methylation status of the DRD4 and COMT genes may serve as biological indicators to evaluate the prevalence of relatively high‐risk psychotic symptoms in MAUD patients.
The present work is focused on the use of electrochemical cathode-reduction method for leaching LiCoO2 produced by spent lithium-ion batteries. The thermodynamics, kinetics, and electrochemical ...impedance spectroscopy analyses are used to determine the probable control mechanism involved in the leaching of cobalt from spent LiCoO2. The leaching efficiencies reached about 90% for cobalt and nearly 94% for lithium using 1.25 mol/L of malic acid and a working voltage of 8 V for 180 min at 70 °C. Kinetics analysis indicates that the leaching process of cobalt could be divided into two stages: the first stage is controlled by a surface chemical reaction, and the second stage is controlled by a combination of the surface chemical reaction and diffusion. Electrochemical impedance spectroscopy, X-ray photoelectron spectroscopy, and transmission electron microscopy analysis show that the combination control at the second stage is related to the form of Co(OH)3 produced during the leaching process of spent LiCoO2. Finally, a novel process for the leaching of cobalt from spent LiCoO2 is proposed.
•A novel process of electrochemical cathode reduction is designed for leaching of spent LiCoO2 batteries.•The thermodynamics, kinetics and EIS are analyzed for understanding the controlling mechanism of leaching process.•The SEM, XPS and TEM are analyzed for clarifying the combination control at second stage of leaching process.
Microporous nitrogen‐doped carbons produced by hydrothermal carbonization of biomass derivative followed by chemical activation showed excellent supercapacitive capacitance performance both in acid ...and base electrolytes.
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