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Mining novel and less utilized thousand grain weight (TGW) related genes are useful for improving wheat yield. In this study, a recombinant inbred line population from a cross between Zhongkemai 138 (ZKM138, high TGW) and Chuanmai 44 (CM44, low TGW) was used to construct a new Wheat 50K SNP array-derived genetic map that spanned 1,936.59 cM and contained 4, 139 markers. Based on this map, ninety-one quantitative trait loci (QTL) were detected for eight grain-related traits in six environments. Among 58 QTLs, whose superior alleles were contributed by ZKM138, QTgw.cib-6A was a noticeable major stable QTL and was also highlighted by bulked segregant analysis with RNA sequencing (BSR-Seq). It had a pyramiding effect on TGW enhancement but no significant trade-off effect on grain number per spike or tiller number, with two other QTLs (QTgw.cib-2A.2 and QTgw.cib-6D), possibly explaining the excellent grain performance of ZKM138. After comparison with known loci, QTgw.cib-6A was deduced to be a novel locus that differed from nearby TaGW2 and TaBT1. Seven simple sequence repeat (SSR) and thirty-nine kompetitive allele-specific PCR (KASP) markers were finally developed to narrow the candidate interval of QTgw.cib-6A to 4.1 Mb. Only six genes in this interval were regarded as the most likely candidate genes. QTgw.cib-6A was further validated in different genetic backgrounds and presented 88.6% transmissibility of the ZKM138-genotype and a 16.4% increase of TGW in ZKM138 derivatives. And the geographic pattern of this locus revealed that its superior allele is present in only 6.47% of 433 Chinese modern wheat varieties, indicating its potential contribution to further high-yield breeding.

ObjectiveTo use systems biology to explore the biomolecular network mechanism of the Jiangtang Tiaozhi Recipe (JTTZR) in the intervention of obese Type 2 diabetes (T2DM) patients with dyslipidemia.MethodsTwelve patients with obese type 2 diabetes mellitus and dyslipidemia (traditional Chinese medicine syndrome differentiation was excess heat syndrome of the stomach and intestines) were treated with JTTZR for 24 weeks, and 12 patients were included in the healthy control group. First, blood samples from 6 patients in each group (disease group before treatment, disease group after treatment, and healthy control group) were collected for RNA microarray analysis. Quantitative polymerase chain reaction (qPCR) was used to validate these target lncRNAs and mRNAs. Finally, a detailed analysis of the differences in the disease group before treatment vs. the healthy control group and the disease group after treatment vs. the disease group before treatment was undertaken. In addition, we focused on disease-related pathways and analyzed the correlation between the differential expression of target lncRNAs and clinical indicators. Results(1) Disease group before treatment vs. healthy control group: There were 557 up-regulated lncRNAs, 273 down-regulated lncRNAs, 491 up-regulated mRNAs, and 1639 down-regulated mRNAs. GO analysis and pathway analysis showed that T2DM may be related to cell proliferation in the forebrain, post-embryonic organ development, calcium signaling pathway. qPCR validation showed that the expression of XLOC-005590 and HNF1A-AS1 as target lncRNAs increased, and this was verified by gene chip analysis. (2) Disease group after treatment vs. disease group before treatment: 128 lncRNAs were upregulated, 32 lncRNAs were downregulated, 45 mRNAs were upregulated, and 140 mRNAs were downregulated. GO analysis and pathway analysis showed that JTTZR may treat T2DM through endosome transport, the insulin signaling pathway, and glycine, serine, and threonine metabolism. qPCR validation showed that in the healthy control group, XLOC_005590 was upregulated, whereas the downstream gene (ECI2) was downregulated in the disease group before treatment. However, after 24 weeks of intervention with JTTZR, XLOC_005590 was downregulated and ECI2 was upregulated compared with the disease group before treatment (0 weeks) (P

Abstract Objective To explore the effects of the autonomous sensory meridian response (ASMR) on the psychological cravings and anxiety of women compulsorily isolated for detoxification. Method Around 122 women were recruited in a female drug detoxification center. Except for the 12‐week training of ASMR, the experimental conditions of the experimental group (n = 60) were the same as those of the control group (n = 62). The addiction Stroop task was used to assess the level of psychological cravings and the State‐Trait Anxiety Inventory was used to assess the level of anxiety. Results After the training, the decrease in state anxiety of the experimental group was larger than that of the control group, and the reaction time of the experimental group in the Stroop was also significantly lower than before the training. Conclusions ASMR could thus reduce to a certain extent the state anxiety and attentional bias for drug‐related clues under signaling psychological cravings among women compulsorily isolated for detoxification. HIGHLIGHTS Intervention effects on psychological cravings and anxiety of women isolated for detoxification Basis for role of ASMR in regulating psychological cravings and anxiety in forced abstainers ASMR intervention reduced forced abstainers’ attentional bias to drug‐related clues

Rhaponticum uniflorum is commonly used as a source for traditional medicines with the main effect of clearing heat. Here, we sequenced the complete chloroplast (cp) genome of R. uniflorum to develop molecular markers for taxonomic classification and species determination of R. uniflorum. It was 152,760 bp in size and has a typical circular structure, including a pair of inverted repeats with 25,205 bp, a large single-copy region with 83,687 bp, and a small single copy region with 18,663 bp. The genome encodes 110 unique genes, including 80 protein-coding, four rRNA and 26 tRNA genes. Phylogenomic analysis shows that R. uniflorum is closely related to the Saussurea. The study is useful for phylogenetic and population genetic studies of Rhaponticum plants.

Four one-dimensional complexes, denoted as [NiL1][Ni(CN)4] (1), [CuL1][Ni(CN)4] (2), [NiL2][Ni(CN)4]·2H2O (3), and [CuL2][Ni(CN)4]·2H2O (4) (L1 = 1,8-dimethyl-1,3,6,8,10,13-hexaaza-cyclotetradecane; L2 = 1,8-dipropyl-1,3,6,8,10,13-hexaazacyclotetradecane) were synthesized by reacting nickel/copper macrocyclic complexes with K2[Ni(CN)4]. Subsequently, the synthesized complexes were characterized using elemental analysis, infrared spectroscopy analysis, thermogravimetric analysis, and X-ray powder diffraction. Single-crystal structure analysis revealed that the Ni(II)/Cu(II) atoms were coordinated by two nitrogen atoms from [Ni(CN)4]2− with four nitrogen atoms from a macrocyclic ligand, forming a six-coordinated octahedral coordination geometry. Nickel/copper macrocyclic complexes were bridged by [Ni(CN)4]2− to construct one-dimensional chain structures in 1–4. The characterization results showed that the four complexes obeyed the Curie–Weiss law with a weak antiferromagnetic exchange coupling.

Anther development is crucial for controlling crop fertility. To elucidate the underlying mechanisms of reproductive development of highland barley (called Qingke in Chinese), two main Qingke cultivars, Zangqing 2000 and Ximala 22, were utilized. Transcriptome analysis showed that lipid, sugar and phenylpropane metabolisms might be the major pathways associated with Qingke male fertility by analyzing the possible common DEGs before anther maturation in both varieties. Additionally, 26 genes related to crop genic male sterility were screened to identify homologous genes for Qingke male sterile lines. Among them, HORVU.MOREX.r3.7HG0634780 (HvtOSC12), an oxidosqualene cyclase, was highlighted as a candidate gene for affecting Qingke male fertility, as it is highly and especially expressed before Qingke anther maturation. Furthermore, HvtOSC12 (including promoter sequence) was cloned by homology-based cloning. The further bioinformatic analysis deduced that MYBs might be one of the transcription factors affecting expression of HvtOSC12 by responding to environmental changes. These results might lay a foundation for the potential applications for the creation of environment-sensitive genic male sterility in Qingke.

In this study, oxidized maltodextrins with a high concentration of carboxyl groups were produced using CuSO4 as a catalyst and H2O2 as an eco-friendly oxidant. Infrared spectroscopy, proton-nuclear magnetic resonance spectroscopy, and thermogravimetric analysis were utilized to examine the structure and properties of oxidized maltodextrins. The reaction conditions were optimized in terms of oxidant content, catalyst content, temperature, pH, and reaction time. The prepared oxidized maltodextrin had a carboxyl group content of 105% under the conditions of 200% molar H2O2, 1% molar catalyst, 55 °C, initial pH = 9.7, and 2 h reaction time. In comparison to the commonly used sodium hypochlorite oxidation process, the carboxyl group content was increased by 58%.

The land use and land cover pattern of the Qinghai-Tibet Plateau (QTP) is an important basis for the structure and function of the QTP ecological barrier. It is of great significance to simulate the land use pattern and landscape ecological risk of the QTP under future scenarios for the construction of the QTP barrier area and to promote the sustainable use of land resources. The QTP was selected as the study area. Based on the spatial pattern of land use in 2010 and 2020, the PLUS model was used to predict the land use patterns of the QTP in 2030 under the two scenarios of natural development and ecological conservation. The landscape ecological risk index was constructed to evaluate the past, present, and future landscape ecological risk of the QTP. The natural break point method was used to divide the landscape ecological risk index into five levels: lower ecological risk, low ecological risk, medium ecological risk, high ecological risk, and higher ecological risk. The results showed that: (1) Under the natural development scenario, the area of cropland, forestland, grassland, and unused land decreased continuously, while the areas of water and built-up land increased gradually. Under the ecological conservation scenario, the areas of forestland and grassland increased by 130 km2 and 2293 km2, respectively, compared with the natural development scenario. (2) Under the natural development scenario, the overall ecological risk of the QTP increased from 2010 to 2030, which showed that the proportions of lower ecological risk area decreased, while the proportion of medium and high ecological risk area increased. Under the ecological conservation scenario, compared with the natural development scenario, the area of lower, low, and high ecological risk increased by 4044 km2, 2484 km2, and 6401 km2, respectively, while the areas of medium and higher ecological risk decreased by 6333 km2 and 6597 km2, respectively.

Assessments of surface urban heat island (UHI) have focused on using remote sensing and land cover data to quantify UHI intensity and spatial distribution within a certain time period by including land cover information. In this study, we implemented a prototype approach to characterize the spatiotemporal variations of UHI using time series of Landsat land surface temperature products and annual land change information. We analyzed UHI distribution and change in Sioux Falls, South Dakota, in the north-central United States and found that the mean UHI intensity in the region was as large as 2.2°C during the period 1986–2017 with an increasing trend of 0.02°C per year within the area with a 5-km non-urban extent. The UHI intensity associated with high intensity urban land cover usually is stronger than with low intensity urban land cover. We evaluated the impact of different non-urban reference extents on UHI variation using different non-urban buffers. The result also suggests that the overall temporal trends of UHI intensity are almost the same when using a 5-km or 10-km non-urban buffer surrounding the urban core. The prototype approach provides a framework to consistently quantify UHI and monitor its change to a large geographic extent.

Abstract Fish sex identification is a basic technique of great importance for both fish genetic studies and fisheries. Due to the sexual reversal phenomenon in many fish species, a simple and rapid molecular identification method for fish genetic sex is urgently needed to suit versatile detection scenarios, such as point-of-need applications. In this study, we took Cynoglossus semilaevis as an example, established a recombinase-aided amplification (RAA)-based method for sex identification, and combined the RAA-detection with two result visualization approaches with distinct features, capillary electrophoresis (CE) and lateral flow dipstick (LFD). Specific primers and probe were designed to specifically detect the sex chromosome W of C. semilaevis in order to distinguish the genetic sex between males, pseudo-males and females. To evaluate the performance of our methods, the genetic sex for twenty-eight males, sixty-eight pseudo-males and fifty-four females were examined with the RAA-based method and classical PCR-based genotyping method, demonstrating the consistent results of sex identification between both methods. The RAA-LFD method is operationally simple, rapid (~ 30 min) and holds great potential for point-of-need applications of fish sex identification, including fishery fields. The method presented here could be effective for identifying fish gender with the ZW karyotype.

The underlying mechanism of the superconducting-to-insulator transition under an applied magnetic field has been a topic of debate for many years. Here, the authors investigate the superconductor-to-insulator transition in 2D films and investigate the nature of the transition as a function of sample dimensions and reveal the importance of the quantum-Griffiths singularity.

The high mountain and gorge area is an typically area, where geological disasters happen frequently. Especially landslide is one of the most serious geological disasters. Recently relative researches on geological disasters showed that landslides had an increasing trends due to the impacts of both climate change and human activities. In this study, Jiangda County in Tibet Autonomous region was selected as our study area, which located in the high mountain and gorge area of the Hengduan Mountain Region. In addition, using the landslide data for 85 sites based on field survey, choosing Slope, River density, Geomorphic type, Precipitation, the distance from the fault, Road density, the ground motion peak acceleration and Lithology as 8 influencing factors on landslide, and then employing the Geodetector model to analyze the impact of various variables on landslide stability. The results showed that 1) according to the volume of landslide, medium and small landslides are main types in Jiangda County; According to its stability, more than 50% of the landslide is in a stable state; according to the danger level, they are mainly divided into Ⅲ, Ⅳ. In space, it is mainly along rivers and roads in Jiangda County, which caused by the limitations of the field survey besides physical factors. Because all 85 landslide survey sites located near rivers, and more than 71% sites are distributed on both sides of the road. 2) The geomorphic type, River density, Road density and the distance from the fault are major factors to affect the stability of the landslide in Jiangda County, its contribution rate are 0.501, 0.477, 0.465 and 0.332, respectively. When the influence factors interact in pairs, the explanatory power of factors is always greater than that of a single factor to the stability of landslides. In other words, when the two influencing factors interact, they always promote the instability of landslides.

Abstract Background The National Chest Pain Center Accreditation Program (CHANGE) is the first hospital-based, multifaceted, nationwide quality improvement (QI) initiative, to monitor and improve the quality of the ST segment elevation myocardial infarction (STEMI) care in China. The QI initiatives, as implementation strategies, include a bundle of evidence-based interventions adapted for implementation in China. During the pandemic of coronavirus disease 2019 (COVID-19), fear of infection with severe acute respiratory syndrome coronavirus 2, national lockdowns, and altered health care priorities have highlighted the program’s importance in improving STEMI care quality. This study aims to minimize the adverse impact of the COVID-19 pandemic on the quality of STEMI care, by developing interventions that optimize the QI initiatives, implementing and evaluating the optimized QI initiatives, and developing scale-up activities of the optimized QI initiatives in response to COVID-19 and other public health emergencies. Methods A stepped wedge cluster randomized control trial will be conducted in three selected cities of China: Wuhan, Suzhou, and Shenzhen. Two districts have been randomly selected in each city, yielding a total of 24 registered hospitals. This study will conduct a rollout in these hospitals every 3 months. The 24 hospitals will be randomly assigned to four clusters, and each cluster will commence the intervention (optimized QI initiatives) at one of the four steps. We will conduct hospital-based assessments, questionnaire surveys among health care providers, community-based household surveys, and key informant interviews during the trial. All outcome measures will be organized using the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) framework, including implementation outcomes, service outcomes (e.g., treatment time), and patient outcomes (e.g., in-hospital mortality and 1-year complication). The Consolidated Framework for Implementation Research framework will be used to identify factors that influence implementation of the optimized QI interventions. Discussion The study findings could be translated into a systematic solution to implementing QI initiatives in response to COVID-19 and future potential major public health emergencies. Such actionable knowledge is critical for implementors of scale-up activities in low- and middle-income settings. Trial registration ChiCTR 2100043319 . Registered on 10 February 2021

To improve corrosion-resistance of shallow-buried concrete urban utility tunnels (UUTs), basalt fiber reinforced polymer (BFRP) bars are applied to reinforce UUTs. As the UUT must have excellent survival capability under accidental explosions, a shallow-buried BFRP bars reinforced UUT (BBRU) was designed and constructed. Repetitive blast experiments were carried out on this BBRU. Dynamic responses, damage evolutions and failure styles of the BBRU under repetitive explosions were revealed. The tunnel roof is the most vulnerable component and longitudinal cracks develop along the tunnel. When the scaled distance is larger than 1.10 m/kg1/3, no cracks are observed in the experiments. When the BBRU is severely damaged, there are five cracks forming and developing along the roof. The roof is simplified as a clamped-supported one-way slab, proved by the observation that the maximum strain of the transverse bar is much larger than that of the longitudinal bar. Dynamic responses of the roof slab are predicted by dynamic Euler beam theory, which can consistently predict the roof displacement under large-scaled-distance explosion. Compared with the UUT reinforced with steel bars, the BBRU has advantages in blast resistance with smaller deflections and more evenly-distributed cracks when the scaled distance is smaller than 1.260 m/kg1/3 and the steel bars enter plastic state. Longer elastic defamation of the BFRP bars endows the UUT more excellent blast resistance under small-scaled-distance explosions.

Abstract Corneal wound healing depends on extracellular matrix (ECM) and topographical cues that modulate migration and proliferation of regenerating cells. In our study, silk films with either flat or nanotopography patterned parallel ridge widths of 2000, 1000, 800 nm surfaces were combined with ECMs which include collagen type I (collagen I), fibronectin, laminin, and Poly-d-Lysine to accelerate corneal wound healing. Silk films with 800 nm ridge width provided better cell spreading and wound recovery than other size topographies. Coating 800 nm patterned silk films with collagen I proves to optimally further increased mouse and rabbit corneal epithelial cells growth and wound recovery. This enhanced cellular response correlated with redistribution and increase in size and total amount of focal adhesion. Transcriptomics and signaling pathway analysis suggested that silk topography regulates cell behaviors via actin nucleation ARP-WASP complex pathway, which regulate filopodia formation. This mechanism was further explored and inhibition of Cdc42, a key protein in this pathway, delayed wound healing and decreased the length, density, and alignment of filopodia. Inhibition of Cdc42 in vivo resulted in delayed re-epithelization of injured corneas. We conclude that silk film nanotopography in combination with collagen I constitutes a better substrate for corneal wound repair than either nanotopography or ECM alone.

Neuroblastoma (NB), as the most common extracranial solid tumor in childhood, is one of the critical culprits affecting children’s health. Given the heterogeneity and invisibility of NB tumors, the existing diagnostic and therapeutic approaches are inadequate and ineffective in early screening and prognostic improvement. With the rapid innovation and development of nanotechnology, nanomedicines have attracted widespread attention in the field of oncology research for their excellent physiological and chemical properties. In this review, we first explored the current common obstacles in the diagnosis and treatment of NB. Then we comprehensively summarized the advancements in nanotechnology-based multimodal synergistic diagnosis and treatment of NB and elucidate the underlying mechanisms. In addition, a discussion of the pending challenges in biocompatibility and toxicity of nanomedicine was conducted. Finally, we described the development and application status of nanomaterials against some of the recognized targets in the field of NB research, and pointed out prospects for nanomedicine-based precision diagnosis and therapy of NB.

ABSTRACT Introduction: Knockdown of fat mass and obesity-associated gene (FTO) can induce N6-methyladenosine (m 6A) ribonucleic acid (RNA) methylation. The objective of this study was to explore the effect of m 6A RNA methylation on atherosclerotic vulnerable plaque by FTO knockdown. Methods: A total of 50 New Zealand white rabbits were randomly divided into pure high-fat group, sham operation group, vulnerable plaque group, empty load group, and FTO knockdown group (10 rabbits/group). Results: Flow cytometry showed that helper T (Th) cells in the FTO knockdown group accounted for a significantly higher proportion of lymphocytes than in the vulnerable plaque group and empty load group (P

In the past decade, China’s new energy has experienced a prosperous development and has become an important main power supply in China. With the promotion of China’s power market–oriented reform, the market-oriented transaction mechanism will play an essential role for China to achieve a large-scale and efficient national allocation of new energy. This study systematically analyzes and designs the principle of China’s new energy cross-provincial marketization mechanism, including those for a compound system such as an interprovincial medium and long-term transaction and spot transaction. The proposed mechanism is validated by its implemental results on a prototype power system with new energy.

Spike compactness (SC) and length (SL) are the components of spike morphology and are strongly related to grain yield in wheat (Triticum aestivum L.). To investigate quantitative trait loci (QTL) associated with SC and SL, a recombinant inbred lines (RIL) population derived from the cross of Bailangmai (BLM, a Tibet landrace) and Chuanyu 20 (CY20, an improved variety) was employed in six environments. Three genomic regions responsible for SC and SL traits were identified on chromosomes 2A and 2D using bulked segregant exome sequencing (BSE-Seq). By constructing genetic maps, six major QTL were repeatedly detected in more than four environments and the best linear unbiased estimation (BLUE) datasets, explaining 7.00–28.56% of the phenotypic variation and the logarithm of the odd (LOD) score varying from 2.50 to 13.22. They were co-located on three loci, designed as QSc/Sl.cib-2AS, QSc/Sl.cib-2AL, and QSc/Sl.cib-2D, respectively. Based on the flanking markers, their interactions and effects on the corresponding trait and other agronomic traits were also analyzed. Comparison analysis showed that QSc/Sl.cib-2AS and QSc/Sl.cib-2AL were possibly two novel loci for SC and SL. QSc/Sl.cib-2AS and QSc/Sl.cib-2D showed pleiotropic effects on plant height and grain morphology, while QSc/Sl.cib-2AL showed effects on spikelet number per spike (SNS) and grain width (GW). Based on the gene annotation, orthologous search, and spatiotemporal expression patterns of genes, TraesCS2A03G0410600 and TraesCS2A03G0422300 for QSc/Sl.cib-2AS, and TraesCS2D03G1129300 and TraesCS2D03G1131500 for QSc/Sl.cib-2D were considered as potential candidate genes, respectively. These results will be useful for fine mapping and developing new varieties with high yield in the future.

To study and model changes in the development of pak choi (Brassica rapa ssp. chinensis Makino), three pak choi cultivars—Xinxiaqing No. 5 (Xinxiaqing 5), Haiqing, and Huawang—were grown in a modern greenhouse. Four structural parameters, including leaf length, leaf width, and plant height and width, were measured regularly every 3 days. The results showed that the changes in plant height and width, and leaf length and width of the three cultivars followed sigmoidal trends. Logistical regression models {Y = K/[1 + (K – L0)/L0 × exp(–r × t)]; Y = K/[1 + (K – L0)/L0 × exp(−r × rad)]} of the leaf length and width accumulated with growth days and with accumulated radiation fit the actual data very well, with the correlation coefficient R2 all greater than 0.98. The R2 values of the plant width accumulation models were all greater than 0.93, whereas the R2 values of the plant height regression models were not robust. In this study, the regression models of changes in plant height and width, and leaf length and width of pak choi were used to study the changes of morphological characteristics and analyze the change rules of pak choi growth and development.

Abuses of most illegal drugs, including methamphetamine, marijuana, cocaine, heroin, and polydrug, are usually in conjunction with alcohol and tobacco. There are similarities and associations between the behavior, gene, and neurophysiology of such abusers, but the neural overlaps of their cue-reactivity and the correlation of neural overlap with drug craving still needs to be further explored. In this study, an Activation Likelihood Estimation (ALE) was performed on brain activation under legal (tobacco, alcohol) and illegal drug cues, for identifying the similarities in brain functions between different craving states. A Comprehensive meta-analysis (CMA) on the correlation coefficient between brain activation and craving scores in the selected literatures with subjective craving reports explained the degree of the craving via brain imaging results. In ALE, co-activation areas of the three cue-reactivity (posterior cingulate, caudate, and thalamus) suggest that the three cue-reactivity may all arouse drug-use identity which is a predictor of relapse and generation of conditioned reflexes under reward memory, thus leading to illegal drug relapses. In CMA, the brain activation was significantly correlated with subjective craving, with a correlation coefficient of 0.222. The neural overlap of tobacco, alcohol and most of the prevalent illegal drug cues not only further helps us understand the neural mechanism of substance co-abuse and relapse, but also provides implications to detoxification. Furthermore, the correlation between brain activation and craving is low, suggesting the accuracy of craving-based quantitative evaluation by neuroimaging remains unclear.

Aiming at the problems of low fault recognition rate， slow convergence speed and difficult parameter selection in the process of fault diagnosis of planetary gearbox based on BP neural network improved by optimization algorithm， a GA-ACO algorithm is proposed to optimize the parameters of neural network. The basic principle and main steps of GA-ACO-BP algorithm are given. At the same time， this method is applied to the fault diagnosis of planetary gearbox. Comparing the performance of ACO-BP neural network algorithm and GA-ACO-BP algorithm， the results show that the convergence speed of ACO Optimized BP neural network is slow and the recognition accuracy is not high， while GA-ACO-BP algorithm can accurately and quickly diagnose and identify the fault of planetary gearbox.

The nuclear reactor coolant pump transferring heat energy inherently brings with it the unsteady flow and inevitably threatens to the safe operation of the pump unit, especially with the pressure pulsation induced by the rotor-stator interaction. In this paper, the characteristics of pressure pulsation of the diffuser in a nuclear reactor coolant pump were investigated by the numerical simulation with experimental validation. Pressure pulsation signals measured synchronously from sensors mounted on the radial diffuser of a model pump were analyzed via Welch’s method. Frequency components induced by the rotor-stator interaction can be revealed by the diameter mode analysis method. The pressure pulsation of the diffuser is dominated by the blade passing frequency and its harmonics, which are free from the effect of flow rate and rotational speed while the corresponding amplitudes are easily affected by different operational conditions and measuring positions. The non-uniformity is much more affected by the rotational speed than the flow rate. This research is helpful for further work to reduce the pressure pulsation for the reactor coolant pump.

Abstract LAT1 (SLC7A5) is one of the representative light chain proteins of heteromeric amino acid transporters, forming a heterodimer with its heavy chain partner 4F2hc (SLC3A2). LAT1 is overexpressed in many types of tumors and mediates the transfer of drugs and hormones across the blood-brain barrier. Thus, LAT1 is considered as a drug target for cancer treatment and may be exploited for drug delivery into the brain. Here, we synthesized three potent inhibitors of human LAT1, which inhibit transport of leucine with IC50 values between 100 and 250 nM, and solved the cryo-EM structures of the corresponding LAT1-4F2hc complexes with these inhibitors bound at resolution of up to 2.7 or 2.8 Å. The protein assumes an outward-facing occluded conformation, with the inhibitors bound in the classical substrate binding pocket, but with their tails wedged between the substrate binding site and TM10 of LAT1. We also solved the complex structure of LAT1-4F2hc with 3,5-diiodo-l-tyrosine (Diiodo-Tyr) at 3.4 Å overall resolution, which revealed a different inhibition mechanism and might represent an intermediate conformation between the outward-facing occluded state mentioned above and the outward-open state. To our knowledge, this is the first time that the outward-facing conformation is revealed for the HAT family. Our results unveil more important insights into the working mechanisms of HATs and provide a structural basis for future drug design.

Abstract Background Wide-awake local anesthesia no tourniquet (WALANT) technique has emerged among hand surgeons with other indications. Surgeries involving pedicled flap and revascularization are no longer used as contraindications. The present study aimed to evaluate the feasibility and merits of the WALANT technique in random skin flap surgery. Methods From May 2018 to March 2019, 12 patients with finger skin defects repaired with random skin flaps were reviewed. Abdominal skin flaps or thoracic skin flaps were used to cover the wound. Both the fingers and the donor sites were anesthetized by the WALANT technique. A 40-mL conventional volume consisted of a mixture of epinephrine and lidocaine. A volume of 5 mL was injected at the distal palmar for nerve block, the other 5 mL was injected around the wound for hemostasis, and the remaining was injected at the donor site of flaps for both analgesia and hemostasis. Baseline data with respect to sex, age, side, type of finger, donor sites, flap size, dosage of anesthetics, usage of finger tourniquet, intraoperative and postoperative pain, hemostasis effect, operation time, Disabilities of the Arm, Shoulder, and Hand Questionnaire (QuickDASH) score, and hospitalization expense, were collected. Results All patients tolerated the procedure, and none of them needed sedation. Single finger skin defect in 8 patients and double finger skin defect occurred in 4 patients; 5 patients were repaired by abdominal skin flaps, and 7 patients were repaired by thoracic skin flaps. The good surgical field visibility was 91.7%. All flaps survived adequately, without necrosis, pulling fingers out, and other complications. The average visual analog scale (VAS) score of the maximal pain was 1.1 in fingers vs. 2.1 in donor sites during the operation. On postoperative day one, the average VAS score of the maximal pain in fingers and donor sites was 1.3 and 1.1, respectively. The average hospitalization expense before reimbursement of the whole treatment was 11% less expensive compared to the traditional method. The average QuickDASH score was 9.1. Conclusions Under wide-awake anesthesia, patients have the ability to control their injured upper extremities consciously, avoiding the complications due to pulling flap pedicles. With the merits of safety, painlessness, less bleeding, and effectivity, the WALANT technique in random skin flaps is feasible and a reliable alternative to deal with finger skin defect.

In order to improve the performance of the sparrow search algorithm (SSA), in this paper, a novel series of SSA variants is proposed by combining SSA with improved Tent chaos mutation (IT), Lévy flights mutation (LF), elite opposition-based learning mutation (EOBL), variable radius mutation (VR) and the combination of IT, LF, EOBL, and VR, namely, ITSSA, LFSSA, EOBLSSA, VRSSA, and CMSSA, respectively. Initially, the performance of these variants is evaluated on a comprehensive set of 31 benchmark test functions. Moreover, the performance of the best algorithm among these variants is compared with 19 state-of-the-art optimization algorithms to validate its performance on 31 benchmark test functions. The convergence and computational complexity of the best variant are also analyzed to test exploration, exploitation, and local optima avoidance. It is then employed on eight real-world constrained engineering problems to further verify its robustness. The experimental results reveal that the best algorithm of SSA variants outperforms other competitors and is highly effective in solving real-life cases.

China’s Yangtze River Basin has an increasingly strong demand for crude oil. As a seaborne import port for crude oil, Ningbo-Zhoushan Port is under pressure to undertake the transshipment of crude oil to various oil terminals in the Yangtze River Basin. To alleviate the stress of crude oil transportation in Ningbo-Zhoushan Port, the port operator proposed the crude oil sea–river transshipment scheme in Nantong Port. Therefore, this paper aims to verify the feasibility of this scheme. We used the discrete event system modeling and entity relationship diagram method to construct the hierarchical and concept models of the Yangtze River Basin’s crude oil sea–river transportation system. Furthermore, we developed corresponding simulation modules on the Witness platform and carried out a simulation experiment of the crude oil sea–river transfer scheme. In the experiment, we analyzed the influence of the transshipment ratio on berth utilization, waiting time, and sailing time of other ports by adjusting the parameter of the transshipment ratio. The experimental results show that when the transshipment rate reaches 100%, the utilization rates of loading and unloading berth in Nantong Port are 4% and 13%, respectively, which evidences that Nantong Port has transshipment potential. At the same time, the simulation experiment’s statistical indicators, such as the utilization rate of oil berths, the queuing time of oil tankers, and the sailing time, not only confirm the feasibility of the crude oil sea–river transshipment scheme of Nantong Port but also confirm that the scheme is helpful to improve crude oil transportation efficiency. The simulation results benefit the port operation decision, and the established model and simulation module can be encapsulated and reused.

The mustache toads Leptobrachium boringii and Leptobrachium liui are two attractive species in Megophryidae, in which adult males have mustache-like keratinized nuptial spines on their upper lip. However, both are under threat due to multiple factors, of which scientific studies are still very limited. In this study, two new complete mitochondrial genomes of L. boringii and L. liui were sequenced, assembled, and annotated based on next-generation sequencing. The mitogenome lengths of L. boringii and L. liui were found to be 17,100 and 17,501 bp, respectively, with both containing 13 protein coding genes, 23 tRNAs, 2 rRNAs, and 1 non-coding control region. Nucleotide diversity analyses indicate that atp8, atp6, and nad2 showed higher nucleotide diversity than cox1, cox3, and cytb. The intraspecific genetic distances among three different populations of L. boringii exceed 4%, and those between two populations of L. liui reach 7%. Phylogenetic relationships support their division into two subfamilies of Megophryidae (Leptobrachiinae and Megophryinae) as well as two species groups within Leptobrachium, corresponding to the number of keratinized nuptial spines (10–48 in the L. boringii species group vs. 2–6 in the L. liui species group). The two new mitogenomes reported in this study provide valuable data for future molecular evolutionary and conservation studies of the genus Leptobrachium and other Megophryidae toads.

During the explosive welding, the bonding interface of welded materials was fast heated due to high strain rate and drastic plastic deformation. The periodical wave interface, with an amplitude of ~300 μm and a period wavelength of ~800 μm, was identifiable as a uniform wave interface formed in the bonding interface. The details of the formation of melting zone and mixing zone of welding materials at the interface were observed. Combined with the Ti-Fe binary phase diagram and the principle of diffusion welding, the phase composition and evolution process of the melting and mixing zone of the bonding interface were investigated by transmission electron microscopy (TEM) and energy dispersive spectrometer (EDS). Significance of the intermetallic compound was found in the mixing zone and melting zone, which was mainly TiFe, TiFe2, TiO2, Fe2O3 and some other intermetallic oxides. Meanwhile, the phenomenon of the titanium agglomeration and oxygen precipitation was observed in the melting zone. The bonding interface could be determined as a mixing welding of mechanical mixing, melting, diffusion and solidification that occurred in the mixing zone, and melting welding and diffusion welding mainly occurred in the melting region.

Qinghai Province is situated deep in inland China, on the Qinghai-Tibet plateau, and it has unique climate change characteristics. Therefore, understanding the temporal and spatial distributions of water vapor in this region can be of great significance. The present study applied global navigation satellite system (GNSS) technology to retrieve precipitable water vapor (PWV) in Qinghai and analyzed its relationship with rainfall and drought. Firstly, radiosonde (RS) data is used to verify the precision of the surface pressure (P) and temperature (T) from the fifth-generation atmosphere reanalysis data set (ERA5) of the European Centre for Medium-Range Weather Forecasts (ECMWF), as well as the zenith troposphere delay (ZTD), calculated based on the data from continuously operating reference stations (CORS) in Qinghai. Secondly, a regional atmospheric weighted mean temperature (Tm) (QH-Tm) model was developed for Qinghai based on P, T, and relative humidity, as well as the consideration of the influence of seasonal changes in Tm. Finally, the PWV of each CORS in Qinghai was calculated using the GNSS-derived ZTD and ERA5-derived meteorological data, and its relationship with rainfall and drought was evaluated. The results show that the ERA5-derived P and T have high precision, and their average root mean square (RMS), mean absolute error (MAE) and bias were 1.06/0.85/0.01 hPa and 2.98/2.42/0.03 K, respectively. The RMS, MAE and bias of GNSS-derived ZTD were 13.2 mm, 10.3 mm and −1.8 mm, respectively. The theoretical error for PWV was 1.98 mm; compared with that of RS- and ERA5-derived PWV, the actual error was 2.69 mm and 2.16 mm, respectively. In addition, the changing trend of GNSS-derived PWV was consistent with that of rainfall events, and it closely and negatively correlated with the standardized precipitation evapotranspiration index. Therefore, the PWV retrieved from GNSS data in this study offers high precision and good feasibility for practical applications; thus, it can serve as a crucial tool for investigating water vapor distribution and climate change in Qinghai.

It is very important to develop a new method of preparing high-performance liquid silicone rubber-reinforcing filler. Herein, the hydrophilic surface of silica (SiO2) particles was modified by a vinyl silazane coupling agent to prepare a new type of hydrophobic reinforcing filler. The structures and properties of modified SiO2 particles were confirmed using Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS), specific surface area and particle size distribution and thermogravimetric analysis (TGA), the results of which demonstrated that the aggregation of hydrophobic particles is greatly reduced. Additionally, the effects of the vinyl-modified SiO2 particle (f-SiO2) content on the dispersibility, rheology, and thermal and mechanical properties of liquid silicone rubber (SR) composites were studied for application toward high-performance SR matrix. The results showed that the f-SiO2/SR composites possessed low viscosity and higher thermal stability, conductivity, and mechanical strength than of SiO2/SR composites. We believe that this study will provide ideas for the preparation of high-performance liquid silicone rubber with low viscosity.

Easy detachment is as important as reliable an attachment to climbing robots in achieving stable climbing on vertical surfaces. To deal with the difficulty of detachment occurring in wheeled and track-type climbing robots using bio-inspired spines, a novel climbing robot utilizing spiny track and dual-rail mechanism is proposed in this paper. The spiny track consists of dozens of spiny feet, and the movement of each spiny foot is guided by the specially designed dual-rail mechanism to achieve reliable attachment and easy detachment. First, the design of the climbing robot and the dual-rail mechanism are presented. Then, the dual-rail model is constructed to analyze the attaching and detaching movements of the spiny feet, and a mechanical model is established to analyze the force distribution on the spiny track. Finally, a robot prototype is developed, and the analysis results are verified by the experiment results. Experiments on the prototype demonstrated that it could climb on various rough vertical surfaces at a speed of 36 mm/s, including sandpaper, brick surfaces, concrete walls with pebbles, and coarse stucco walls.

Abstract Background Hepatocellular carcinoma (HCC) is a common digestive tumor with great heterogeneity and different overall survival (OS) time, causing stern problems for selecting optimal treatment. Here we aim to establish a nomogram to predict the OS in HCC patients. Methods International Cancer Genome Consortium (ICGC) database was searched for the target information in our study. Lasso regression, univariate and multivariate cox analysis were applied during the analysis process. And a nomogram integrating model scoring and clinical characteristic was drawn. Results Six mRNAs were screened out by Lasso regression to make a model for predicting the OS of HCC patients. And this model was proved to be an independent prognostic model predicting OS in HCC patients. The area under the ROC curve (AUC) of this model was 0.803. TCGA database validated the significant value of this 6-mRNA model. Eventually a nomogram including 6-mRNA risk score, gender, age, tumor stage and prior malignancy was set up to predict the OS in HCC patients. Conclusions We established an independent prognostic model of predicting OS for 1–3 years in HCC patients, which is available to all populations. And we developed a nomogram on the basis of this model, which could be of great help to precisely individual treatment measures.

Abstract Background It had been shown that High-flow nasal cannula (HFNC) is an effective initial support strategy for patients with acute respiratory failure. However, the efficacy of HFNC for patients with COVID-19 has not been established. This study was performed to assess the efficacy of HFNC for patients with COVID-19 and describe early predictors of HFNC treatment success in order to develop a prediction tool that accurately identifies the need for upgrade respiratory support therapy. Methods We retrospectively reviewed the medical records of patients with COVID-19 treated by HFNC in respiratory wards of 2 hospitals in Wuhan between 1 January and 1 March 2020. Overall clinical outcomes, the success rate of HFNC strategy and related respiratory variables were evaluated. Results A total of 105 patients were analyzed. Of these, 65 patients (61.9%) showed improved oxygenation and were successfully withdrawn from HFNC. The PaO2/FiO2 ratio, SpO2/FiO2 ratio and ROX index (SpO2/FiO2*RR) at 6h, 12h and 24h of HFNC initiation were closely related to the prognosis. The ROX index after 6h of HFNC initiation (AUROC, 0.798) had good predictive capacity for outcomes of HFNC. In the multivariate logistic regression analysis, young age, gender of female, and lower SOFA score all have predictive value, while a ROX index greater than 5.55 at 6 h after initiation was significantly associated with HFNC success (OR, 17.821; 95% CI, 3.741-84.903 p

For the purpose of manufacturing the automotive B-pillars with tailored properties, based on the proposed partition induction heating-quenching process, the partition controllable induction heating-stamping process of high-strength boron alloyed steel plates with designable temperature patterns is experimentally investigated. The temperature distribution of the various low temperature region patterns on the steel plates can be arbitrarily customized after heating for 30 s by properly arranging the magnetizer groups. Furthermore, the temperature field of the test B-pillar is customized. The temperature in the low temperature region of the heated B-pillar is 600 °C, which is lower than the start temperature of austenite transformation (AC1 = 750 °C), while the temperature in the high temperature region is 950 °C, which realizes fully austenization. After stamping and quenching, different microstructures are generated in the test B-pillar corresponding to the different temperature regions. The microstructures of the stamped test B-pillar in the low temperature region are mixture microstructures of ferrite + pearlite, while the fine lath martensite microstructures are transformed in the high temperature region. In terms of mechanical properties, the tensile strengths according to the low temperature region and high temperature regions are 438 and 1610 MPa, while the uniform elongation is 14.8% and 6.5% respectively, which meets the design requirements of the B-pillars with tailored properties. The specimens with a tensile strength difference ratio greater than 1: 3.5 and an elongation difference ratio greater than 1: 2.2 are obtained, which indicates the partition controllable induction heating-stamping process provides a new way to achieve automobile lightweight and significantly increasing the safety.

In this study, we assembled and described the complete chloroplast genome (cp) of Sinosenecio baojingensis Ying Liu & Q.E. Yang (Asteraceae) for the first time. The cp genome is 151,315 bp in length and exhibits a typical quadripartite structure, consisting of a large single-copy (LSC) region of 83,445 bp, a small single-copy (SSC) region of 18,172 bp, and a pair of inverted repeat regions (IRs) of 24,849 bp. A total of 133 genes were annotated, including 88 protein-coding genes (one pseudo gene), 37 tRNA genes (tRNAs), and eight ribosomal RNA genes (rRNAs). Further, the phylogenetic analysis based on eight complete chloroplast genomes indicates that S. baojingensis is shown to be a sister to S. jishouensis. The complete chloroplast genome of S. baojingensis provides significant molecular markers for the studies on phylogeny and species identification of this genus.

For the manufacturing of automotive B-pillar parts with tailored properties, a multi-objective optimization of partition temperature of steel sheet is conducted to obtain the magnetic conductor parameters corresponding to optimal mechanical properties by using Response Surface Methodology (RSM) and Non-dominated Sorting Genetic Algorithm (NSGA-II). Based on the proposed zone induction heating-stamping, the numerical simulations are implemented to optimize the design variables (width, thickness, spacing of the magnetic conductor) on the objective functions (the maximum Z1 and minimum temperature Z2). The regression model of quadratic polynomial is established, the significance of each item is analyzed by analysis of variance (ANOVA). The Pareto-optimal fronts are obtained by NSGA-II algorithm. The results reveal that the most significant factor for Z1 and Z2 is the linear term of width and thickness respectively. On the basis of Pareto optimization solution set, the final optimal solution is selected through decision-making. In other words, the objective functions Z1 = 950 °C and Z2 = 650 °C are obtained, the corresponding magnetic conductor parameters as design variables are Width = 9.05 mm, Thickness = 2.96 mm and Spacing = 2.19 mm. Through the simulation and experimental verification of rectangular steel sheet, the multi-objective optimization of partition temperature of steel sheet by NSGA-II using RSM is effective. The regression model provides theoretical and experimental basis for the customization of steel sheet temperature field under the zone induction heating-stamping.

ObjectiveTo explore the effects of nifedipine tablets combined with magnesium sulfate on blood coagulation indexes, oxidative stress and levels of NO and ET-1 in patients with Pregnancy-induced hypertension syndrome (PIH).MethodsA total of 110 patients with hypertension during pregnancy were admitted to our hospital from January 2020 to January 2021. According to the random number table method, 110 patients were divided into the control group and the therapy group, with 55 cases in each group. The blood pressure levels (systolic and diastolic blood pressure), coagulation indexes (TT, PT, APTT, Fib), oxidative stress indexes (LPO, MDA, SOD), vascular endothelial function (ET-1, NO), clinical efficacy and adverse reactions of the two groups were compared.ResultsAfter therapy, the systolic blood pressure and diastolic blood pressure of the two groups were significantly decreased, and the therapy group was significantly lower than the control group (P < 0.05). After therapy, PT, TT, and APTT in two groups were significantly increased, and Fib was significantly decreased, and PT, TT, APTT in the therapy group were higher than those in the control group, and Fib was lower than that in the control group (P < 0.05). After therapy, LPO and MDA in two groups were significantly decreased, and SOD was significantly increased, and LPO and MDA in the therapy group were lower than those in the control group, and SOD was higher than that in the control group (P < 0.05). After therapy, ET-1 in two groups were significantly increased, and NO and ET-1/NO was significantly decreased, and ET-1 in the therapy group was higher than that in the control group, and NO and ET-1/NO were lower those in the control group (P < 0.05). The total clinical effective rate of patients in the therapy group was 94.5%, and in the control group was 81.8%, the therapy group was significantly better than the control group (P < 0.05). The total incidence of adverse reactions in the therapy group was 7.3%, and in the control group was 21.8%, the therapy group was significantly lower than the control group (P < 0.05).ConclusionNifedipine tablets combined with magnesium sulfate in the treatment of PIH can improve the blood coagulation function of patients, reduce oxidative stress damage, adjust the serum levels of ET-1 and NO, and improve the clinical efficacy.

Psychological stress plays an important role in hair loss, but the underlying mechanisms are not well-understood, and the effective therapies available to regrow hair are rare. In this study, we established a chronic restraint stress (CRS)-induced hair growth inhibition mouse model and performed a comprehensive analysis of metabolomics and transcriptomics. Metabolomics data analysis showed that the primary and secondary metabolic pathways, such as carbohydrate metabolism, amino acid metabolism, and lipid metabolism were significantly altered in skin tissue of CRS group. Transcriptomics analysis also showed significant changes of genes expression profiles involved in regulation of metabolic processes including arachidonic acid metabolism, glutathione metabolism, glycolysis gluconeogenesis, nicotinate and nicotinamide metabolism, purine metabolism, retinol metabolism and cholesterol metabolism. Furthermore, RNA-Seq analyses also found that numerous genes associated with metabolism were significantly changed, such as Hk-1, in CRS-induced hair growth inhibition. Overall, our study supplied new insights into the hair growth inhibition induced by CRS from the perspective of integrated metabolomics and transcriptomics analyses.

A rotating magnet-based mechanical antenna (RMBMA) is a new promising paradigm which can significantly reduce both the size and the power consumption of the super-low frequency electromagnetic transmitter. To further reveal the effects of the rotational motion on transmission, this paper investigates the performance analysis of MSK (Minimum Shift Keying)-based RMBMA for the first time. Initially, based on the framework of MSK-based RMBMA, both the information loading of RMBMA and the control strategies of the motor are proposed, such that the impacts of the step response induced by the motor on the information loading are characterized. Then, the transmission capacity of the MSK-based RMBMA is derived in the closed form. The results indicate that increasing output torque or decreasing inertia load can enhance the transmission capacity. Finally, numerical simulations using a realistic system model demonstrate the validity of the proposed performance analysis. The simulation results show that when the inertia is less than 0.0128 kg∙m2 and the symbol rate is less than 4 bit/s, the bit error rate is less than 10%, thereby improving the transmission capacity. The proposed comprehensive design principles of RMBMA provide guidance for system design and practical implementation.

Background Ischemic stroke (IS) is a complex polygenic disease with a strong genetic background. The relationship between the ANRIL (antisense non-coding RNA in the INK4 locus) in chromosome 9p21 region and IS has been reported across populations worldwide; however, these studies have yielded inconsistent results. The aim of this study is to clarify the types of single-nucleotide polymorphisms on the ANRIL locus associated with susceptibility to IS using meta-analysis and comprehensively assess the strength of the association. Methods Relevant studies were identified by comprehensive and systematic literature searches. The quality of each study was assessed using the Newcastle-Ottawa Scale. Allele and genotype frequencies were extracted from each of the included studies. Odds ratios with corresponding 95% confidence intervals of combined analyses were calculated under three genetic models (allele frequency comparison, dominant model, and recessive model) using a random-effects or fixed-effects model. Heterogeneity was tested using the chi-square test based on the Cochran Q statistic and I2 metric, and subgroup analyses and a meta-regression model were used to explore sources of heterogeneity. The correction for multiple testing used the false discovery rate method proposed by Benjamini and Hochberg. The assessment of publication bias employed funnel plots and Egger’s test. Results We identified 25 studies (15 SNPs, involving a total of 11,527 cases and 12,216 controls maximum) and performed a meta-analysis. Eight SNPs (rs10757274, rs10757278, rs2383206, rs1333040, rs1333049, rs1537378, rs4977574, and rs1004638) in ANRIL were significantly associated with IS risk. Six of these SNPs (rs10757274, rs10757278, rs2383206, rs1333040, rs1537378, and rs4977574) had a significant relationship to the large artery atherosclerosis subtype of IS. Two SNPs (rs2383206 and rs4977574) were associated with IS mainly in Asians, and three SNPs (rs10757274, rs1333040, and rs1333049) were associated with susceptibility to IS mainly in Caucasians. Sensitivity analyses confirmed the reliability of the original results. Ethnicity and individual studies may be the main sources of heterogeneity in ANRIL. Conclusions Our results suggest that some single-nucleotide polymorphisms on the ANRIL locus may be associated with IS risk. Future studies with larger sample numbers are necessary to confirm this result. Additional functional analyses of causal effects of these polymorphisms on IS subtypes are also essential.

Effectively enhancing the activity of inhibitory neurons has great therapeutic potentials since their reduced function/activity has significant contributions to pathology in various brain diseases. We showed previously that NMDAR positive allosteric modulator GNE-8324 and M-8324 selectively increase NMDAR activity on the inhibitory neurons and elevates their activity in vitro and in vivo. Here we examined the impact of long-term administering M-8324 on the functions and transcriptional profiling of parvalbumin-containing neurons in two representative brain regions, primary auditory cortex (Au1) and prelimbic prefrontal cortex (PrL-PFC). We found small changes in key electrophysiological parameters and RNA levels of neurotransmitter receptors, Na+ and Ca2+ channels. In contrast, large differences in cell adhesion molecules and K+ channels were found between Au1 and PrL-PFC in drug-naïve mice, and differences in cell adhesion molecules became much smaller after M-8324 treatment. There was also minor impact of M-8324 on cell cycle and apoptosis, suggesting a fine safety profile.

Explosive hardening of commercial pure titanium plate was conducted by a thin-layer high-detonation-velocity explosive. The nanoindentation and Vickers hardness tests of the treated titanium plates along the depth of shock loading were performed. The microstructures along the depth were characterized by using different methods, including X-Ray Diffraction, Optical Microscopy, Electron Back-Scattered Diffraction and Transmission Electron Microscopy. Experimental results showed that large-depth gradient hardness distribution with depth of 2.5 mm was produced in CP titanium by explosive hardening. There are two gradient hardened layers, ultra-hardened layer with a depth of 0–40 μm and a hardness increase of ∼400%, sub-hardened layer with a depth of 40 μm-2500 μm and a hardness increase of 54.3%. Gradient microstructures with different characteristics were observed, including gradient α-ω phase transition, gradient grain size, gradient twining and gradient dislocation. The area of gradient microstructure is consistence with that of gradient hardness distribution. Grain refinement/α-ω phase transition mainly contributed to hardness sharply increasing in ultra-hardened layer. High-density dislocation/twining mainly contributed to hardness increasing in the sub-hardened layer. Finally, the formation mechanism of gradient microstructures and grain refinement mechanism was detailly discussed.

Summary: The BET-bromodomain protein BRD4 uses two bromodomains to target acetyl-histones and other domains to recruit P-TEFb and other transcription factors to stimulate transcription of proto-oncogenes and key cell identity genes. Recent studies show that its ability to form phase-separated condensates that cluster preferentially at the super-enhancer regions of target genes is key for BRD4 to exert its functions. Here, we describe the identification of a natural product called PCG from polygonum cuspidatum Sieb.et Zucc., a traditional Chinese medicinal herb, that directly binds to BRD4. This binding inhibits BRD4 phase separation, turns dynamic BRD4 nuclear condensates into static aggregates, and effectively shuts down transcription of BRD4-dependent genes. Thus, through PCG we have discovered a BET inhibitor that not only selectively targets BRD4 but also works by suppressing phase separation, a mechanism of action that is different from those of the other known BET inhibitors.

BackgroundTransfer delay provokes prolongation of prehospital time, which contributes to treatment delay that endangers patients with ST-segment elevation myocardial infarction (STEMI). A key constraint in reducing transfer delay is the shortage of emergency healthcare workers. This study was to explore the influence of the quality and quantity of healthcare professionals at emergency medical stations on transfer delay and in-hospital mortality among STEMI patients.MethodsA cross-sectional study using mixed methods was conducted at 89 emergency stations in 9 districts in China's Shenzhen province. Based on a sample of 31 hospitals, 1,255 healthcare professionals, and 3,131 patients with STEMI, a generalized linear model was used to explore the associations between the quality and quantity of healthcare professionals and transfer delay and in-hospital mortality among STEMI patients. Qualitative data were collected and analyzed to explore the reasons for the lack of qualified healthcare professionals at emergency medical stations.ResultsThe analysis of the quantity of healthcare professionals showed that an increase of one physician per 100,000 individuals was associated with decreased transfer delay for patients with STEMI by 5.087 min (95% CI −6.722, −3.452; P < 0.001). An increase of one nurse per 100,000 individuals was associated with decreased transfer delay by 1.471 min (95% CI −2.943, 0.002; P=0.050). Analysis of the quality of healthcare professionals showed that an increase of one physician with an undergraduate degree per 100,000 individuals was associated with decreased transfer delay for patients with STEMI by 8.508 min (95% CI −10.457, −6.558; P < 0.001). An increase of one nurse with an undergraduate degree per 100,000 individuals was associated with decreased transfer delay by 6.645 min (95% CI −8.218, −5.072; P < 0.001). Qualitative analysis illustrated that the main reasons for low satisfaction of healthcare professionals at emergency medical stations included low income, limited promotion opportunities, and poor working environment.ConclusionsThe quantity and quality of emergency healthcare professionals are key factors influencing transfer delay in STEMI patients. The government should increase the quantity of healthcare professionals at emergency medical stations, strengthen the training, and improve their performance by linking with clinical pathways to enhance job enthusiasm among emergency healthcare professionals.

Background. Although direct pars repair using a pedicle screw-rod-hook system has achieved satisfactory results in patients with spondylolysis, its application in adults with low-grade isthmic spondylolisthesis is rarely reported. Objective. To assess the surgical effect of reduction and direct repair surgery with a pedicle screw-rod-hook system combined with autogenous bone grafts in adult patients with low-grade isthmic spondylolisthesis. Methods. Sixty-four adult patients with low-grade isthmic spondylolisthesis underwent reduction and direct repair using a pedicle screw-rod-hook system in our department from September 2009 to April 2018. The clinical efficacy was evaluated by clinical and radiological assessments. Results. The average follow-up was 52.15 ± 9.96 months. The visual analog scale (VAS) scores (VAS-lumbar and VAS-leg) and Oswestry Disability Index (ODI) at the final follow-up (FFU) were significantly lower than the preoperative levels P

Objective. Posterior instrumented fusion is the most widely accepted surgical treatment for spinal stenosis with degenerative lumbar scoliosis (DLS). However, long fusion can affect daily activities due to lumbar stiffness. Dynamic stabilization has been introduced to overcome the drawbacks of fusion in recent years. This study aimed to compare the outcomes of dynamic stabilization (Dynesys system) with posterior instrumented fusion for the management of spinal stenosis with DLS. Methods. This study retrospectively reviewed 65 consecutive patients with spinal stenosis and DLS who were undergoing surgical treatment between January 2013 and December 2017. Among them, 34 patients (Dynesys group) had fenestration decompression and Dynesys stabilization, whereas 31 patients (fusion group) underwent posterior instrumented fusion. Clinical outcomes, radiographic data, and postoperative complications were compared between the two groups. Results. The mean number of fixed segments was 3.6 ± 0.9 in the Dynesys group and 4.2 ± 1.0 in the fusion group. Lower average values of operating time and blood loss were observed in the Dynesys group (P0.05). The visual analog scale for back pain (VASback), oswestry disability index (ODI), and lumbar stiffness disability index (LSDI) scores of the Dynesys group were lower compared with the fusion group (P0.05). Conclusion. Both dynamic stabilization and instrumented fusion can improve the clinical outcomes of patients with spinal stenosis and mild DLS. Compared to instrumented fusion, dynamic stabilization has the advantages of less invasion and motion preservation.

Intervertebral disc degeneration (IDD) is closely related to osmolarity, which fluctuates with daily activities, and hyperosmolarity may be a contributor to nucleus pulposus (NP) cells apoptosis. Aquaporin-3 (AQP-3) belongs to the family of aquaporins and mainly transports water and other small molecular proteins, which is reduced with the aging of the intervertebral disc. ERK1/2 pathway is one type of mitogen-activated protein kinase (MAPK) and is associated with cellular apoptosis. This study was aimed to investigate the effects of AQP-3 on NP cells apoptosis induced by a hyperosmolarity and focused on the role of the ERK1/2 signaling pathway. We found that NP apoptosis could be induced by hyperosmolarity (550 mOsm/kg), and downregulation of AQP-3 and inhibition of ERK1/2 could be simultaneously observed. Therefore, lentivirus was used to enhance the expression of AQP-3 to compare apoptosis between AQP-3-overexpressed NP cells and the control NP cells. The results showed that apoptosis could be alleviated by overexpression of AQP-3 and the activity of ERK1/2 could also be promoted. Furthermore, we found that the inhibitor U0126 could partly aggravate apoptosis of the AQP-3-overexpressed NP cells. In summary, our results suggested that overexpression of AQP-3 could protect against hyperosmolarity-induced NP cell apoptosis via promoting the activity of the ERK1/2 pathway. This study may shed light on a better understanding of the pathologic mechanism of IDD and bring AQP-3 into the therapeutic approaches for IDD treatment.

PurposeWe have previously reported that VEGF-B is more potent than VEGF-A in mediating corneal nerve growth in vitro and in vivo, and this stimulation of nerve growth appears to be different from stimulation of angiogenesis by these same ligands, at least in part due to differences in VEGF receptor activation. VEGF signaling may be modulated by a number of factors including receptor number or the formation of receptor hetero- vs. homodimers. In endothelial cells, VEGF receptor heterodimer (VEGR1/R2) activation after ligand binding and subsequent phosphorylation alters the activation of downstream signaling cascades. However, our understanding of these processes in neuronal cell types remains unclear. The purpose of this study was to identify the presence and distribution of VEGF Receptor-Ligand interactions in neuronal cells as compared to endothelial cells.MethodsPC12 (rat neuronal cell line), MAEC (mouse aortic endothelial cell line), MVEC (mouse venous endothelial cell line) and HUVEC (human umbilical venous endothelial cell line; control group) were used. Cells were acutely stimulated either with VEGF-A (50 ng/μL) or VEGF-B (50 ng/μL) or "vehicle" (PBS; control group). We also isolated mouse trigeminal ganglion cells from thy1-YFP neurofluorescent mice. After treatment, cells were used as follows: (i) One group was fixed in 4% paraformaldehyde and processed for VEGFR1 and VEGFR2 immunostaining and visualized using confocal fluorescence microscopy and Total Internal Reflection (TIRF) microscopy; (ii) the second group was harvested in cell lysis buffer (containing anti-protease / anti-phosphatase cocktail), lysed and processed for immunoprecipitation (IP; Thermo Fisher IP kit) and immunoblotting (IB; LI-COR® Systems). Immunoprecipitated proteins were probed either with anti-VEGFR1 or anti-VEGFR2 IgG antibodies to evaluate VEGFR1-R2-heterodimerization; (iii) a third group of cells was also processed for Duolink Proximity Ligation Assay (PLA; Sigma) to assess the presence and distribution of VEGF-receptor homo- and heterodimers in neuronal and endothelial cells.ResultsTIRF and fluorescence confocal microscopy revealed the presence of VEGFR1 co-localized with VEGFR2 in endothelial and PC12 neuronal cells. Cell lysates immunoprecipitated with anti-VEGFR1 further validated the existence of VEGFR1-R2 heterodimers in PC12 neuronal cells. Neuronal cells showed higher levels of VEGFR1-R2 heterodimers as compared to endothelial cells whereas endothelial cells showed higher VEGFR2-R2 homodimers compared to neuronal cells as demonstrated by Duolink PLA. Levels of VEGFR1-R1 homodimers were very low in neuronal and endothelial cells.ConclusionsDifferences in VEGF Receptor homo- and heterodimer distribution may explain the differential role of VEGF ligands in neuronal versus endothelial cell types. This may in turn influence VEGF activity and regulation of neuronal cell homeostasis.