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Recently, molecular generation models based on deep learning have attracted significant attention in drug discovery. However, most existing molecular generation models have serious limitations in the context of drug design wherein they do not sufficiently consider the effect of the three-dimensional (3D) structure of the target protein in the generation process. In this study, we developed a new deep learning-based molecular generator, SBMolGen, that integrates a recurrent neural network, a Monte Carlo tree search, and docking simulations. The results of an evaluation using four target proteins (two kinases and two G protein-coupled receptors) showed that the generated molecules had a better binding affinity score (docking score) than the known active compounds, and the generated molecules possessed a broader chemical space distribution. SBMolGen not only generates novel binding active molecules but also presents 3D docking poses with target proteins, which will be useful in subsequent drug design. The code is available at https://github.com/clinfo/SBMolGen.

As we all know, the complexity and diversity of complex sample are confronting with challenge of high-sensitive mass spectrometry analysis, especially direct mass spectrometry. The work proposed a two-dimensional carbon microfiber fractionation (2DμCFs) system for the reduction of ion suppression effects in electrospray ionization mass spectrometry (ESI-MS). The 2DμCFs system can on-line fractionated the complex sample into strong-polar, medium-polar and weak-polar fractions for sequential MS analysis. Direct analysis brings about the strong ion suppression effect up to 85%, but the fractionated analysis of 2DμCFs system can distinctly reduce the ion suppression effect to less than 43%, even close to none. And the fractionated analysis not only decrease the number of analytes of direct analysis, but also narrows down the polarity range of analytes within the droplets of ESI, contributing to the homogeneous distribution to reduce the ion suppression effect. As an example, the 2DμCFs system coupled with tandem mass spectrometry (MS/MS) was applied for fractionated analysis of Radix Puerariae extract in 4.5 min. Compared with direct MS/MS, the 2DμCFs-MS/MS shows the lower ion suppression and the more ionic species (m/z). In addition, and most of ionic species detected by the 2DμCFs-MS/MS, are the same as those by HPLC MS/MS. Furthermore, the 2DμCFs-MS/MS exhibit the good analysis repeatability of real sample with the RSDs less than 10.32% (intra-day), 7.12% (inter-day) and 14.28% (inter-batch of CFs and ACFs). The carbon fibers (CFs) and active carbon fibers (ACFs) columns, as the key parts, are conducive to achieve on-line fractionation of compounds based on the difference of polarity. The 2DμCFs system has the merits of on-line, speediness, low-pressure and recycle. More importantly, such fast and high-throughput method is advantageous for comprehensive screening of complex samples in drug, clinical, environment and plant.

The stress hormone ethylene plays a key role in plant adaptation to adverse environmental conditions. Nitrogen (N) is the most quantitatively required mineral nutrient for plants, and its availability is a major determinant for crop production. Changes in N availability or N forms can alter ethylene biosynthesis and/or signaling. Ethylene serves as an important cellular signal to mediate root system architecture (RSA) adaptation, N uptake and translocation, ammonium toxicity, anthocyanin accumulation, and premature senescence, thereby adapting plant growth and development to external N status. Here, we review the ethylene-mediated morphological and physiological responses and highlight how ethylene transduces the N signals to the adaptive responses. We specifically discuss the N-ethylene relations in rice, an important cereal crop in which ethylene is essential for its hypoxia survival. This article is protected by copyright. All rights reserved.

Bio-fertilizer practice considers not only economical but also environmentally friendly, sustainable agriculture. Endophytes can play important beneficiary roles in plant development, directly, indirectly, or synergistically. In this study, the majority of our endophytic actinobacteria were able to possess direct plant growth-promoting (PGP) traits, including auxin (88%), ammonia (96%), siderophore production (94%), and phosphate solubilization (24%), along with cell-wall degrading enzymes such as protease (75%), cellulase (81%), lipase (81%), and chitinase (18%). About 45% of tested strains have an inhibitory effect on the phytopathogen

B-box (BBX) proteins are one of the zinc-finger transcription factor that plays a critical role in plant development, growth, and multiple stress responses. Although

Deoxyribonucleic acid (DNA) has evolved to be a naturally selected, robust biomacromolecule for gene information storage, and biological evolution and various diseases can find their origin in uncertainties in DNA-related processes (e.g. replication and expression). Recently, synthetic DNA has emerged as a compelling molecular media for digital data storage, and it is superior to the conventional electronic memory devices in theoretical retention time, power consumption, storage density, and so forth. However, uncertainties in the in vitro DNA synthesis and sequencing, along with its conjugation chemistry and preservation conditions can lead to severe errors and data loss, which limit its practical application. To maintain data integrity, complicated error correction algorithms and substantial data redundancy are usually required, which can significantly limit the efficiency and scale-up of the technology. Herein, we summarize the general procedures of the state-of-the-art DNA-based digital data storage methods (e.g. write, read, and preservation), highlighting the uncertainties involved in each step as well as potential approaches to correct them. We also discuss challenges yet to overcome and research trends in the promising field of DNA-based data storage.

Fatty acyl reductases (FARs) catalyse the reduction of fatty acyl-coenzyme A (CoA) or -acyl carrier protein (ACP) substrates to primary fatty alcohols, which play essential roles in lipid metabolism in plants. However, the mechanism by which FARs are involved in male reproduction is poorly defined. Here, we found that two maize allelic mutants, ms25-6065 and ms25-6057, displayed defective anther cuticles, abnormal Ubisch body formation, impaired pollen exine formation and complete male sterility. Based on map-based cloning and CRISPR/Cas9 mutagenesis, Zm00001d048337 was identified as ZmMs25, encoding a plastid-localized FAR with catalytic activities to multiple acyl-CoA substrates in vitro. Four conserved residues (G101, G104, Y327 and K331) of ZmMs25 were critical for its activity. ZmMs25 was predominantly expressed in anther, and was directly regulated by transcription factor ZmMYB84. Lipidomics analysis revealed that ms25 mutation had significant effects on reducing cutin monomers and internal lipids, and altering the composition of cuticular wax in anthers. Moreover, loss of function of ZmMs25 significantly affected the expression of its four paralogous genes and five cloned lipid metabolic male-sterility genes in maize. These data suggest that ZmMs25 is required for anther development and male fertility, indicating its application potential in maize and other crops.

The diffusion of e-commerce has played a significant role in recent rural economic development in China. E-commerce is also considered as an efficient channel to alleviate poverty in rural China. Voluminous studies have investigated the contribution of e-commerce to agricultural development, yet it is lacking empirical evidence as to the effects of e-commerce on rural poverty alleviation. Since the year of 2014, in order to develop rural e-commerce, Chinese government launched the National Rural E-commerce Comprehensive Demonstration Project. This gradual involvement policy offered a natural experiment for evaluation of e-commerce. Based on village-level survey data from rural China and Heckit method, our study finds that rural e-commerce has a significantly positive effect on rural income. Moreover, the effect is inverted U-shaped for the relative-poverty villages. The estimation of the propensity scores matching model confirms that the results are robust. The following policy recommendations are proposed: (1) policy support to rural e-commerce should prioritize the poverty-stricken villages. By doing so, the marginal income effects of e-commerce will be maximized. (2) Investment in internet infrastructure and establishment of human resources for e-commerce in rural areas will have spillover effects, increasing rural income through the “digital dividend”.

Taxane compounds have attracted wide attention due to the basic chemical structure of taxol as an alternative anticancer drug. The full-scan tandem mass spectrometry (MS/MS) fragmentation behaviors of seven taxane compounds were studied. For taxanes of Sc-T and Sc-T-Xyl types, diagnostic product ions are originated from a cleavage in the ester bond of the C

BACKGROUND The biliary system and related diseases have been one of the key research objects of digestive system diseases, and intestinal microecology has been a hot topic in recent years. Bile entering the intestine through the biliary system has been proven to have an important relationship with the biodiversity of intestinal flora, and the homeostasis of intestinal microecology will also change with the occurrence of biliary diseases. OBJECTIVE The aim of this study is to summarize studies on the combination of the biliary system and intestinal microecology, in order to explore the research history, present situation and future trend of the study on the combination of biliary system and intestinal microecology. METHODS The literatures from 2000-01-01 to 2022-02-28 in the Web of Science core database were searched, and 180 articles were screened according to the inclusion criteria. HistCite Pro and VOSviewer software were used to analyze the relevant indicators of bibliometrics and draw knowledge maps. Microsoft Excel 2019 was used for charting. RESULTS Through a bibliometric analysis of 180 papers. From 2000-01-01 to 2002-02-28, especially since 2013, the number of articles published in this field has been increasing. The global citation score (GCS) of the articles was 4751, with an average of 26.39 citations per article. The local citation score (LCS) is 89. At present, "SCIENTIFIC REPORTS" is the journal with the most publications, and “GUT” is the most authoritative journal in this field. The United States plays a leading role in global research, , and China is developing rapidly. The research of Karlsen TH, Schnabl B and Brenner DA in this field has been widely recognized. CONCLUSIONS At present and in the future, research will focus on the intestinal microecology itself. How to simulate the natural intestinal microecology or develop intestinal microecological agents for the benefit of patients with biliary tract diseases is widely considered.

Mizoroki-Heck reaction of unstrained aryl ketone with acrylate/styrene is accomplished via palladium-catalyzed ligand-promoted C-C bond cleavage. Various (hetero)aryl ketones are compatible in the reaction, affording the alkene product in good to excellent yields. Further applications in the late-stage olefination of some drugs, natural products, and fragrance-derived aryl ketones demonstrate the synthetic utility of this protocol. By employing ketone as both the directing group and the leaving group, 1,2-bifunctionalization is achieved via sequential ortho-C-H alkylation/ipso-Heck olefination.

Wetland is an important carbon pool, and the degradation of wetlands causes the loss of organic carbon and total nitrogen. This study aims to explore how wetland degradation succession affects soil organic carbon (SOC) and total nitrogen (TN) contents in alpine wetland. A field survey of 180 soil-sampling profiles was conducted in an alpine wetland that has been classified into three degradation succession stages. The SOC and TN contents of soil layers from 0 to 200 cm depth were studied, including their distribution characteristics and the relationship between soil water content (SWC) and microtopography. The results showed that SOC and TN of different degradation succession gradients followed the ranked order of Non Degradation (ND) > Light Degradation (LD) > Heavy Degradation (HD). SWC was positively correlated with SOC and TN (p

An epoxy resin/powder curing agent crack-repair material (EPCRM) was developed to overcome the limitations of the existing materials used to seal asphalt pavement cracks. The EPCRM was prepared by ...

Conversion of the numerous aryl ketones into aryl electrophiles via Ar–C(O) cleavage remains a challenging yet highly desirable transformation in Sonogashira-type coupling. Herein, we report a pall...

Soft actuators with perception capability are essential for robots to intelligently interact with humans and the environment. However, existing perceptive soft actuators require complex integration and coupling between the discrete functional units to achieve autonomy. Here, we report entirely soft actuators with embodied sensing, actuation, and control at the single-unit level. This is achieved by synergistically harnessing the mechanosensing and electrothermal properties of liquid metal (LM) to actuate the thermally responsive liquid crystal elastomer (LCE). We create multifunctional LM circuits on the LCE surface using a simple and facile methodology based on magnetic printing. The fluidic LM circuit can not only be utilized as a conformable resistive heater but also as a sensory skin to perceive its own deformation. Moreover, the rational design of the LM circuits makes it possible to achieve biomimetic autonomous actuation in response to mechanical stimuli such as pressure or strain. In addition, the intrinsic stretchability of LM allows us to create 3D spring-like actuators via a simple prestretch step, and complex helical motions can be obtained upon mechanical stimulation. This work provides a unique and simple design for autonomous soft robotics with embodied intelligence.

Wet clutches are widely used in vehicle transmission systems to start and shift. The temperature field of the wet clutch components is influenced by friction and is closely related to the vehicle p...

C3-Arylation of indoles with aryl ketones is accomplished via palladium-catalyzed ligand-promoted Ar-C(O) cleavage and subsequent C-H arylation of indole. Various (hetero)aryl ketones are compatible in this reaction, affording the corresponding 3-arylindoles in moderate to good yields. Further introduction of an indole moiety into the natural products desoxyestrone and evodiamine demonstrate the synthetic utility of this protocol.

With the operation of China’s large aircraft, operational safety has become an important issue. The manufacturer uses operation data and design data to carry out safety assessments in the operation phase. Operation safety assessment evaluates whether the conclusion of the safety assessment is still valid and analyzes the safety margin of the aircraft in the operating environment. Model-based civil aircraft operation safety assessment method uses the model-based ideology to propose a technical method of operating safety assessment based on the failure propagation model. The relevant practice also shows that this method is effective and can improve efficiency and accuracy.

Studies have shown that reinforced paper-based friction material with 600 µm carbon fiber length possesses a high dynamic friction coefficient but is subjected to abrasive wear during sliding contact. This work is devoted to further investigate the effect of operating variables on this friction material subjected to high operating conditions. A pin-on-disc test was carried out to determine the tribological behavior of this friction material sliding against 65Mn steel. The friction and wear rate results from measurements were discussed. The highest friction value of about 0.3 was obtained by varying the applied load at 120 N while the lowest friction value close to 0.02 was obtained when the sliding speed was 0.026 m/s. Increasing the sliding speed above 0.30 m/s caused constant temperature (175 °C) to fluctuate due to high friction heat generation on the sliding surface. The highest wear rate was 1.42 × 10−15m3/Nm by varying the sliding speed at 1.31 m/s. In contrast, the lowest wear rate was 2.1 × 10−16m3/Nm when the temperature was at 400 °C.

The temperature field of the wet clutch is an important factor that influences the vehicle transmission performance. In order to predict and prolong the service life of the wet clutch, a test bench is built, and an accelerated life test is carried out based on the actual working conditions. Then, according to the variation of the friction coefficient and the maximum radial temperature difference, the sliding temperature field is analyzed in different periods. By introducing four evaluation indexes, a temperature field evaluation system is established and verified. With the help of this evaluation system, the temperature fields during running-in and unstable stages are compared, and the thermal failure mechanism of the friction disc is analyzed. In the stable stage, the influence of rotational speed, oil pressure and lubricant flow on the temperature field are investigated. The results of this study can guide the design and control of the friction components in the wet clutch.

Liquid metal (LM) has shown potential values in different areas. Attempts to implement LM are tending to develop new functions and make it versatile to improve its performance for practical applications. Here, we present an unprecedented LM-integrated ultra-elastic microfiber with distinctive features for wearable electronics. The microfiber with a polyurethane shell and an LM core was continuously generated by using a sequenced microfluidic spinning and injection method. Due to the precise fluid manipulation of microfluidics, the resultant microfiber could be tailored with tunable morphologies and responsive conductivities. We have demonstrated that the microfiber could act as dynamic force sensor and motion indicator when it was embedded into elastic films. In addition, the values of the LM-integrated ultra-elastic microfiber on energy conversions such as electro-magnetic or electro-thermal conversions have also been realized. These features indicate that LM-integrated microfiber will open up new frontiers in LM-integrated materials and the wearable electronics field.

Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells has limited the efficacy of immunotherapeutic approaches. The T cell receptor expresses one of two highly homologous chains [T cell receptor β-chain constant (TRBC) domains 1 and 2] in a mutually exclusive manner, making it a promising target. We previously described an antibody with unique TRBC1 specificity (Jovi-1). Here we demonstrate specificity redirection by rational design using structure-guided computational biology to generate a TRBC2-specific antibody (KFN). This permitted the generation of paired reagents (chimeric antigen receptor-T cell) specific for TRBC1 and TRBC2, with preclinical evidence to support their efficacy in T cell malignancies.

Bacterial endophytes are well-acknowledged inoculants to promote plant growth and enhance their resistance toward various pathogens and environmental stresses. In the present study, 71 endophytic strains associated with the medicinal plant Thymus roseus were screened for their plant growth promotion (PGP), and the applicability of potent strains as bioinoculant has been evaluated. Regarding PGP traits, the percentage of strains were positive for the siderophore production (84%), auxin synthesis (69%), diazotrophs (76%), phosphate solubilization (79%), and production of lytic enzymes (i.e., cellulase (64%), lipase (62%), protease (61%), chitinase (34%), and displayed antagonistic activity against Verticillium dahliae (74%) in vitro. The inoculation of strain XIEG05 and XIEG12 enhanced plant tolerance to salt stress significantly (p < 0.05) through the promotion of shoot, root development, and reduced the activities of antioxidant enzymes (SOD, POD, and CAT), compared with uninoculated controls in vivo. Furthermore, inoculation of strain XIEG57 was capable of reducing cotton disease incidence (DI) symptoms caused by V. dahliae at all tested salt concentrations. The GC-MS analysis showed that many compounds are known to have antimicrobial and antifungal activity. Our findings provide valuable information for applying strains XIEG05 and XIEG12 as bioinoculant fertilizers and biological control agent of cotton under saline soil conditions.

Unbound granular materials (UGM) in permeable pavement will experience large numbers of infiltration during their service-life. The frequently changed moisture not only affects the cooling effect of permeable pavement, but also influences the mechanical behaviors of UGM. However, evidence is lacking to state the influence of infiltration on the behaviors of UGM, which is commonly in fully permeable pavement. Considering the influence of infiltration, this study conducted experimental tests to investigate the effect on the water-retaining and bearing capacity of UGM. With the water-retaining tests, the water-retaining rate in the whole structure and at different depths was analyzed under different infiltration numbers and duration. The results showed that the water-retaining rate increased with the extension of the infiltration duration. The infiltration duration had a significant influence on the water-retaining capacity of UGM, while the infiltration number had little. The difference in the water-retaining rate between the top and bottom layers was up to 2.56%. The water-retaining capacity of the integrated structure was hardly affected due to the dissimilarity of the water-retaining rate at different depths. With infiltrations, the fine aggregate in the upside structure migrated downward to the lower structure, resulting in a reduction in water-retaining rate in the upper structure and an increase at the bottom. In addition, the mechanical behaviors were evaluated by the traditional California Bearing Ratio (CBR) and repeated CBR tests under five infiltrations. The first and second infiltration had a significant influence on the CBR of UGM. With two infiltrations, the plastic strain increased by 57.8% via the repeated CBR tests. The resilient strain had an increase by 36.52% and the equivalent modulus decreased by 28.7% with the first infiltration. The first infiltration presented a critical influence on the bearing capacity of UGM and the effect decreased with the increase in the infiltration number. These findings will enrich the behaviors investigation of UGM and promote its application in the fully permeable pavement.

DBC1 has been characterized as a key regulator of physiological and pathophysiological activities, such as DNA damage, senescence and tumorigenesis. However, the mechanism by which the functional stability of DBC1 is regulated has yet to be elucidated. Here, we report that the ubiquitination-mediated degradation of DBC1 is dynamically regulated by the E3 ubiquitin ligase SIAH2 and deubiquitinase OTUD5 under hypoxic stress. Mechanistically, hypoxia promoted the competitive binding of SIAH2 with OTUD5 to DBC1, resulting in the ubiquitination and subsequent degradation of DBC1 through the ubiquitin–proteasome pathway. Siah2 knockout inhibited tumor cell proliferation and migration, which could be rescued by double knockout of Siah2/DBC1. Human tissue microarray analysis further revealed that the SIAH2/DBC1 axis was responsible for tumor progression under hypoxic stress. These findings define a key role of the hypoxia-mediated SIAH2-DBC1 pathway in the progression of human breast cancer and provide novel insights into the metastatic mechanism of breast cancer.

With the rapid development of science and technology, information technology has gradually matured. The integration of a lot of complicated information has gradually spawned the technology of big data. Under the adjustment of relevant technicians, big data has also been applied in many fields. The government attaches great importance to the physical health of college students, and monitoring the development of college students’ physical health must be consistent with the concept of coconstruction, cogovernance, and sharing. In this article, advanced technologies such as cloud, Internet, mobile computer, and data fusion are applied to the products in the medical field. Under the basic principle of “patient-centered,” a digital and visual model is established. Through information technology, patients can realize limited medical treatment. The sharing of resources promotes the optimization of medical service processes. The method used in this article is big data analysis. Big data is widely used after high-performance analysis to achieve the purpose of reducing cost, shortening time, increasing artificial intelligence decision-making, and analysis trend accuracy. It can be concluded from the research in this article that the improved DCFA algorithm is used to optimize the SVM and the original FA algorithm to optimize the SVM algorithm for example verification, and the algorithm in this article is optimized by 35% compared with the traditional algorithm.

To investigate the effects of short stud arrangement on flexural behavior of steel-UHPC composite decks, a static bending test was conducted on a full-scale segmental specimen and a parametric analysis was executed based on a validated finite-element model. The test results showed that when UHPC crack width reached 0,10 mm, the measured strain of UHPC was 1568 με, accounting for 47% of the material ultimate tensile strain. And the corresponding nominal stress of UHPC was largely over the material cracking stress. The parametric analysis results showed that increasing stud spacing from 200 mm to 300 mm increased the UHPC cracking load by 9,7% because of a lower composite action; compared with the normal arrangement, studs arranged in groups with the same amount could increase the UHPC cracking load by 11,1% while maintaining the combined effect. However, this was under the condition that the steel and UHPC partially interacted.