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Power integrity analysis is an essential step in power distribution network (PDN) sign-off to ensure the performance and reliability of chips. However, with the growing PDN size and increasing scenarios to be validated, it becomes very time- and resource-consuming to conduct full-stack PDN simulation to check the power integrity for different test vectors. Recently, various works have proposed machine learning–based methods for PDN power integrity prediction, many of which still suffer from large training overhead, inefficiency, or non-scalability. Thus, this article proposed an efficient and scalable framework for the worst-case power integrity prediction, which can handle general tasks including dynamic noise prediction and bump current prediction. The framework first reduces the spatial and temporal redundancy in the PDN and input current vector and then employs efficient feature extraction as well as a novel convolutional neural network architecture to predict the worst-case power integrity. Experimental results show that the proposed framework consistently outperforms the commercial tool and the state-of-the-art machine learning method with only 0.63–1.02% mean relative error and 25–69× speedup for noise prediction and 0.22–1.06% mean relative error and 24–64× speedup for bump current prediction.

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Secondhand smoke (SHS) exposure is associated with negative emotions in adolescents, but the association between SHS exposure and negative emotions has been understudied, especially in low- and middle-income countries. Hence, we studied the association between SHS exposure and negative emotions among 12-15-year-old non-smoking adolescents from 63 low- and middle-income countries (LMICs).We calculated the pooled prevalence of SHS exposure, loneliness, and anxiety in 12-15-year-old non-smoking adolescents. Multivariable logistic regression was used to evaluate country-specific associations between SHS exposure and negative emotions, after adjusting for important confounders. Meta-analyses were performed to evaluate the overall, regional, and country-income level pooled associations.Of the adolescents included in the analysis, 34.88 % had less than daily SHS exposure and 13.41 % were exposed to SHS daily. The overall prevalence of loneliness and anxiety in the adolescents was 10.51 % and 8.95 %, respectively. Exposure to SHS in the past 7 days was associated with loneliness and anxiety, with odds ratios (95 % confidence intervals) of 1.15 (1.09-1.21) and 1.24 (1.17-1.31), respectively. These positive associations were observed in girls, but not in boys. In addition, there was a positive dose-response relationship between the day of exposure to SHS and loneliness and anxiety.The GSHS data were obtained from a self-report questionnaire and the participants were only adolescents in school.Our study revealed a positive association between SHS exposure and negative emotions among non-smoking adolescents from LMICs.

Phthalates are a group of neurotoxicants with cognitive-disrupting potentials. Given the structural diversity of phthalates, the corresponding neurotoxicity is dramatically altered. To identify the potential contributions of different phthalates on the process of cognitive impairment, data of 836 elders from the NHANES 2011–2014 cycles were used. Survey-weighted logistic regression and principal component analysis-weighted quantile sum regression (PCA-WQSR) models were applied to estimate the independent and combined associations of 11 urinary phthalate metabolites with cognitive deficit [assessed by 4 tests: Immediate Recall (IR), Delayed Recall (DR), Animal Fluency (AF), and Digit Symbol Substitution test (DSST] and to identify the potential phthalate with high weight. Laboratory mice were further used to examine the effect of phthalates on cognitive function and to explore the potential mechanisms. In logistic regression models, MBzP was the only metabolite positively correlated with four tests, with ORs of 2.53 [quartile 3 (Q3)], 2.26 (Q3), 2.89 (Q4) and 2.45 (Q2), 2.82 (Q4) for IR, DR, AF and DSST respectively. In PCA-WQSR co-exposure models, low-molecular-weight (LMW) phthalates were the only PC positively linked to DSST deficit (OR: 1.93), which was further validated in WQSR analysis (WQS OR7 − phthalates: 1.56 and WQS OR8 − phthalates: 1.55); consistent with the results of logistic regression, MBzP was the dominant phthalate. In mice, butyl benzyl phthalate (BBP), the parent phthalate of MBzP, dose-dependently reduced cognitive function and disrupted hippocampal neurons. Additionally, the hippocampal transcriptome analysis identified 431 differential expression genes, among which most were involved in inhibiting the neuroactive ligand‒receptor interaction pathway and activating the cytokine‒cytokine receptor interaction pathway. Our study indicates the critical role of BBP in the association of phthalates and cognitive deficits among elderly individuals, which might be speculated that BBP could disrupt hippocampal neurons, activate neuroinflammation and inhibit neuroactive receptors. Our findings provide new insight into the cognitive-disrupting potential of BBP.

We conducted a comprehensive meta-analysis of all available trials to evaluate the efficacy and safety of oestrogen and selective oestrogen receptor modulators as adjunctive treatment for women with schizophrenia.Multiple databases were searched from the inception until March 2022. Only randomized, double-blind, placebo-controlled studies (randomized controlled trials; RCTs) were included. Mean differences (MDs) and their 95% confidence intervals (CIs) were calculated using random effects models.The meta-analysis included six estradiol versus placebo studies (n=724) and seven raloxifene versus placebo studies (n=419), covering a total of 1,143 patients. Adjunctive estradiol outperformed the placebo in terms of the Positive and Negative Syndrome Scale (PANSS) total score (MD=-7.29; 95% CI=-10.67 to -3.91; IOur meta-analysis showed that estradiol and raloxifene are effective and safe adjunctive treatments that improve schizophrenia symptoms in women. Moreover, the effects of estradiol and raloxifene differed in terms of timing and dosage. Both are promising adjunctive treatments that merit further study.

An efficient nitrogen doping strategy is developed to accelerate the disorder-to-order phase transition of Pt3Co catalyst, and the as-prepared ordered Pt3Co shows a PEMFC power density of 1.27 W cm−2 at 0.6 V.

The spread of Coronavirus Disease 2019 (COVID-19) has decreased the willingness to choose public transport where travellers are more likely to be infected due to intensive passenger flow, in which case it is hard to attract passenger volume if the subjective well-being of travellers is not improved. However, the traditional measurement of travel evaluation may be not applicable to the context of the pandemic and it is necessary to analyse the changes in the internal mechanisms of travel well-being to avoid the loss of passengers. Based on structural equation modelling, this paper explored the internal relationship between the constructs of travel well-being and emphasised the significance of taking psychological factors into consideration in the post COVID-19 pandemic. The results show that travel satisfaction with the anti-pandemic related service quality of public transport is related to overall travel well-being, which can be used as a key part of well-being measurement scale design in the future. The results also indicate that, due to negative mood on the affective level induced by COVID-19, travel satisfaction on the cognitive level is not directly but indirectly related to travel choice behaviour through overall travel well-being. Compared to travel satisfaction, travel well-being is more extensive and covers travel satisfaction to some extent. Therefore, instead of studying travel satisfaction simply, taking travel well-being as the dependent variable to identify shortages existing in public transport will provide a more accurate perspective for policymakers in the post COVID-19 pandemic.

The composition of marine aerosol is quite complex, and its sources are diverse. Across the East China Sea (ECS) and the Yellow Sea (YS), multi-dimensional analysis of marine aerosols was conducted. The characteristics of carbonaceous aerosols and gaseous pollutants were explored through in situ ship-based observation, MERRA-2 reanalysis datasets and TROPOMI data from Sentinel-5P satellite. Black carbon (BC)’s average concentration is 1.35 ± 0.78 μg/m3, with high-value BC observed during the cruise. Through HYSPLIT trajectory analysis, sources of BC were from the northern Eurasian continent, the Shandong Peninsula, the ECS and Northwest Pacific Ocean (NWPO). The transport of marine sources like ship emissions cannot be ignored. According to the absorption Angstrom exponent (AAE), BC originates from biomass burning (BB) in the shortwave band (~370 nm) and from fossil fuel combustion in the longwave band (~660 nm). Organic carbon (OC), sulfate (SO42−) and BC report higher Angstrom exponent (AE) while dust and sea salt reveal lower AE, which can be utilized to classify the aerosols as being fine- or coarse-mode, respectively. OC has the highest AE (ECS: 1.98, YS: 2.01), indicating that anthropogenic activities could be a significant source. The process of biomass burning aerosol (BBA) mixed with sea salt could contribute to the decline in BBA’s AE. Ship emissions may affect the distribution of tropospheric nitrogen dioxide (NO2) in the ECS, especially during the COVID-19 pandemic. Tropospheric NO2 over the YS has the highest value (up to 12 × 1015 molec/cm2). Stratospheric NO2 has a ladder-like distribution from north to south, and the variation gradient was lower than that in the troposphere. Carbon monoxide (CO) accumulates in the south and east of the ECS and the east of the YS, while the variation over the eastern YS is relatively frequent. Seas near the Korean Peninsula have extremely high CO concentration (up to 1.35 × 1017 molec/cm2).

Leak monitoring is essential for the intelligent operation and maintenance of marine systems, and can effectively prevent catastrophic accidents on ships. In response to this challenge, a machine vision-based leak model is proposed in this study and applied to leak detection in different types of marine system in complex engine room environments. Firstly, an image-based leak database is established, and image enhancement and expansion methods are applied to the images. Then, Standard Convolution and Fast Spatial Pyramid Pooling modules are added to the YOLOv5 backbone network to reduce the floating-point operations involved in the leak feature channel fusion process, thereby improving the detection speed. Additionally, Bottleneck Transformer and Shuffle Attention modules are introduced to the backbone and neck networks, respectively, to enhance the feature representation performance, select critical information for the leak detection task, and suppress non-critical information to improve detection accuracy. Finally, the proposed model’s effectiveness is verified using leak images collected by the ship’s video system. The test results demonstrate that the proposed model exhibits excellent recognition performance for various types of leak, especially for drop-type leaks (for which the accuracy reaches 0.97).

DNA–protein interaction is one of the most crucial interactions in biological processes. However, the technologies available to study DNA–protein interactions are all based on DNA hybridization; however, DNA hybridization is not highly specific and is relatively low in efficiency. RNA-guided DNA recognition is highly specific and efficient. To overcome the limitations of technologies based on DNA hybridization, we built a DNA-binding protein capture technology based on the clustered regularly interspaced palindromic repeats (CRISPR)–dead Cas9 (dCas9) system and transient genetic transformation, termed reverse chromatin immunoprecipitation based on CRISPR–dCas9 system (R-ChIP–dCas9). In this system, dCas9 was fused with Strep-Tag II to form a fusion protein for StrepTactin affinity purification. Transient transformation was performed for the expression of dCas9 and guide RNA (gRNA) to form the dCas9–gRNA complex in birch (Betula platyphylla) plants, which binds to the target genomic DNA region. The dCas9–gRNA–DNA complex was crosslinked, then the chromatin was sonicated into fragments, and purified using StrepTactin beads. The proteins binding to the target genomic DNA region were identified using mass spectrometry. Using this method, we determined the upstream regulators of a NAM, ATAF, and CUC (NAC) transcription factor (TF), BpNAC090, and 32 TFs potentially regulating BpNAC090 were identified. The reliability of R-ChIP–dCas9 was further confirmed by chromatin immunoprecipitation, electrophoretic mobility shift assays, and yeast one-hybrid. This technology can be adapted to various plant species and does not depend on the availability of a stable transformation system; therefore, it has wide application in identifying proteins bound to genomic DNA.

Metagenomic data generated from environmental samples is increasingly common in the analysis of modern and ancient biological communities. To obtain taxonomic profiles from this type of data, DNA sequences are aligned against large genomic reference databases and the lowest common ancestor (LCA) needs to be inferred for each sequence with multiple alignments. To date, efforts have mainly focused on improving the speed, sensitivity and specificity of alignment tools, and little effort has been applied to the LCA algorithm that generates the taxonomic profiles from alignments. We present ngsLCA, a command-line toolkit with two separate modules: the main program (in C/C++) performing LCA inference, and an R package for generating tables and visualisations of the taxonomic profiles. ngsLCA processed large datasets in BAM/SAM alignment format 4–11 times faster and used less memory compared to other available programs. It is compatible with the NCBI taxonomy and has flexible parameter settings. Furthermore, the toolkit offers functions for filtering, contamination removal, taxonomic clustering, and multiple ways of visualising the generated taxonomic profiles. ngsLCA bridges a gap in current metagenomic analyses by supplying a computationally light, easy-to-use, accurate, fast and flexible LCA algorithm with R functions for processing and illustrating the taxonomic profiles.

Human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection worldwide. Until now, there are no licenced vaccines or effective antiviral drugs against RSV infections. In our previous work, we found 2-((1H-indol-3-yl)thio/sulfinyl)-N-pheny acetamide derivatives (4-49 C and 1-HB-63) being a novel inhibitor against RSV

Long non-coding RNA (lncRNA) is a non-protein-coding RNA with a length of more than 200 nucleotides. Studies have shown that lncRNAs have vital impacts on various pathological processes and participate in the development of human diseases, usually through acting as competing endogenous RNAs to modulate miRNA expression and biological functions. lncRNA HOXA Cluster Antisense RNA 3 (HOXA-AS3) was a newly discovered lncRNA and has been demonstrated to be abnormally expressed in many diseases. Moreover, HOXA-AS3 expression was closely correlated with the clinicopathologic characteristics in cancer patients. In addition, HOXA-AS3 exhibited significant properties in regulating several biological processes, including cell proliferation, invasion, and migration. Furthermore, HOXA-AS3 has provided promising values in the diagnosis, prognosis, and therapeutic strategies of several diseases such as liver cancer, glioma, lung cancer, oral cancer, gastric cancer, and even atherosclerosis. In this review, we discuss the abnormal expression of HOXA-AS3 in several human disorders and some pathobiological processes and its clinical characteristics, followed by a summary of HOXA-AS3 functions, regulatory mechanisms, and clinical application potential.

Paliperidone is an atypical antipsychotic as effective as other atypical antipsychotics for schizophrenia. However, few studies have explored the efficacy of paliperidone for treatment-resistant schizophrenia. This study aimed to compare the efficacy and safety of paliperidone extended release (ER) versus olanzapine in schizophrenia patients with either poor treatment response or intolerable adverse effects due to standardized antipsychotic therapy.This 12-week randomized, double-blind, multicenter study compared the treatment efficacy on psychotic symptoms, cognitive functions, and tolerance between paliperidone ER (6-15 mg/d, n = 45) and olanzapine (10-30 mg/d, n = 41) in treatment-resistant or treatment-intolerant patients with schizophrenia. The severity of psychotic symptoms was evaluated by the Positive and Negative Syndrome Scale and the Clinical Global Impression Severity of Illness Scale. The cognitive functions were assessed by the MATRICS Consensus Cognitive Battery. In addition, the metabolic impacts were evaluated by weight gain and waist circumference.Patients with either paliperidone ER or olanzapine treatment showed apparent improvement in psychotic symptoms, without significant intergroup difference. Twelve-week paliperidone ER or olanzapine treatment did not improve the cognitive functions. Both paliperidone ER and olanzapine treatment caused significant increase in weight and waist circumference, and olanzapine had a greater impact on waist circumference than paliperidone ER. In addition, both drugs were well tolerated.Paliperidone ER could be a safe alternative for treatment-resistant schizophrenia.

Suxiao Jiuxin Pill (SJP) is a well-known traditional Chinese medicine drug used to manage heart diseases. This study aimed at determining the pharmacological effects of SJP in acute myocardial infarction (AMI), and the molecular pathways its active compounds target to induce coronary artery vasorelaxation. Using the AMI rat model, SJP improved cardiac function and elevated ST segment. LC-MS and GC-MS detected twenty-eight non-volatile compounds and eleven volatile compounds in sera from SJP-treated rats. Network pharmacology analysis revealed eNOS and PTGS2 as the key drug targets. Indeed, SJP induced coronary artery relaxation via activation of the eNOS-NO pathway. Several of SJP’s main compounds, like senkyunolide A, scopoletin, and borneol, caused concentration-dependent coronary artery relaxation. Senkyunolide A and scopoletin increased eNOS and Akt phosphorylation in human umbilical vein endothelial cells (HUVECs). Molecular docking and surface plasmon resonance (SPR) revealed an interaction between senkynolide A/scopoletin and Akt. Vasodilation caused by senkyunolide A and scopoletin was inhibited by uprosertib (Akt inhibitor) and eNOS/sGC/PKG axis inhibitors. This suggests that senkyunolide A and scopoletin relax coronary arteries through the Akt-eNOS-NO pathway. In addition, borneol induced endothelium-independent vasorelaxation of the coronary artery. The Kv channel inhibitor 4-AP, KCa2+ inhibitor TEA, and Kir inhibitor BaCl2 significantly inhibited the vasorelaxant effect of borneol in the coronary artery. In conclusion, the results show that Suxiao Jiuxin Pill protects the heart against acute myocardial infarction.

Metallic bipolar plates (BPPs) are key components in the proton-exchange membrane fuel cell (PEMFC), which can replace traditional fossil fuels as a kind of clean energy. However, these kinds of plates, characterized by micro-channels with a high ratio between depth and width, are difficult to fabricate with an ultra-thin metallic sheet. Then, ultrasonic-vibration-assisted stamping is performed considering the acoustic softening effect. Additionally, the influence of various vibration parameters on the forming quality is analyzed. The experimental results show that ultrasonic vibration can obviously increase the channel depth. Among the vibration parameters, the vibration power has the maximum influence on the depth, the vibration interval time is the second, and the vibration duration time is the last. In addition, the rolling direction will affect the channel depth. When the micro-channels are parallel to the rolling direction, the depth of a micro-channel is the largest. This means that the developed ultrasonic-vibration-assisted stamping process is helpful for improving the forming limitation of micro-channels used for the bipolar plates in PEMFC.

GRAS transcription factors belong to the plant-specific protein family. They are not only involved in plant growth and development but also in plant responses to a variety of abiotic stresses. However, to date, the SCL32(SCARECROW-like 32) gene conferring the desired resistance to salt stresses has not been reported in plants. Here, ThSCL32, a homologous gene of Arabidopsis thaliana AtSCL32, was identified. ThSCL32 was highly induced by salt stress in Tamarix hispida. ThSCL32 overexpression in T. hispida gave rise to improved salt tolerance. ThSCL32-silenced T. hispida plants were more sensitive to salt stress. RNA-seq analysis of transient transgenic T. hispida overexpressing ThSCL32 revealed significantly enhanced ThPHD3 (prolyl-4-hydroxylase domain 3 protein) gene expression. ChIP-PCR further verified that ThSCL32 probably binds to the novel cis-element SBS (ACGTTG) in the promoter of ThPHD3 to activate its expression. In brief, our results suggest that the ThSCL32 transcription factor is involved in salt tolerance in T. hispida by enhancing ThPHD3 expression.

An intelligent agent-based supply chain simulation model, in which each enterprise/consumer is represented by an agent, is designed. There are six layers in this supply chain simulation model: raw material providers, component manufacturers, product assemblers, product holders, retailers, and final customers. Each entity in the supply chain represented by an agent has five components: interface, task distribution, business processing activities, knowledge management and decision support, and information storage. A detailed agent structure is designed and various functions of an agent including communication among agents are described. Issues in the supply chain integration, information sharing among supply chain partners, demand forecasting, supply chain risk management, and automated communication and negotiation, could be simulated and studied by using the proposed system. Based on the proposed supply chain simulation model, a generic six-layer prototype mobile phone supply chain simulation system is designed, developed and implemented. The system allows a user to setup and adjust a large number of parameters, including (1) simulation period, loan and saving interest rates; (2) customers' behavior and market demand; (3) each retailer's initial cash, loan, market share, inventories, Order Amount Policy and Order Point Strategy; (4) each product holder's initial cash, loan, market share, inventories, Order Amount Policy, Order Point Strategy and inventory strategy; (5) each assembler's and component agent's initial cash, loan, inventories, Order Amount Policy, Order Point Strategy, production strategy, and production capacities; and (6) each material provider's initial cash, loan, inventory, production strategy, and production capacities. Extensive simulation studies are carried out to examine and compare many supply chain management strategies and agent behaviors. This system can be used to test which strategy is most suitable in certain environments, The generic supply chain simulation system developed can be used in a number of ways, including: as an analysis tool for entity in a supply chain from the entity's perspective; as a tool for studying supply chain coordination and integration from the perspective of an entire supply chain, or portion of it; as a tool to design supply chains by answering "what-if" questions.

Spectral winding of complex eigenenergies represents a topological aspect unique in non-Hermitian systems, which vanishes in one-dimensional (1D) systems under the open boundary conditions (OBC). In this work, we discover a boundary spectral winding in two-dimensional non-Hermitian systems under the OBC, originating from the interplay between Hermitian boundary localization and non-Hermitian non-reciprocal pumping. Such a nontrivial boundary topology is demonstrated in a non-Hermitian breathing Kagome model with a triangle geometry, whose 1D boundary mimics a 1D non-Hermitian system under the periodic boundary conditions with nontrivial spectral winding. In a trapezoidal geometry, such a boundary spectral winding can even co-exist with corner accumulation of edge states, instead of extended ones along 1D boundary of a triangle geometry. An OBC type of hybrid skin-topological effect may also emerge in a trapezoidal geometry, provided the boundary spectral winding completely vanishes. By studying the Green's function, we unveil that the boundary spectral winding can be detected from a topological response of the system to a local driving field, offering a realistic method to extract the nontrivial boundary topology for experimental studies., 10 pages, 7 figures. Comments are welcome

Lycium ruthenicum is an important ecoeconomic thorny shrub. In this study, the L. ruthenicum plants of a clone showed two types of ‘fewer leaves without thorn’ and ‘more leaves with thorns’ under the same condition after transplanting. Microscopic observation revealed that the apical buds of the thornless (Thless) and thorny (Thorny) branches should be selected as materials for further study. RNA-Seq analysis showed that the KEGG pathway of starch and sucrose metabolism and differentially expressed genes of sugar transport protein 13 (SUT13), sucrose synthase (SUS), trehalose-phosphate phosphatase (TPP) and trehalose-phosphate synthase (TPS) were significantly up-regulated in Thorny. The results of qRT-PCR confirmed the accuracy and credibility of the RNA-Seq. The content of sucrose in Thorny was significantly higher than that in Thless, but the content of trehalose-6-phosphate (T6P) was opposite. Leaf-clipping treatments reduced sucrose content and inhibited the occurrence/development of branch-thorns; exogenous sucrose of 16 g l−1 significantly promoted the occurrence and growth of branch-thorns, and the promotion effects were significantly higher than those treated with non-metabolizable sucrose analogs (isomaltolose and melitose). These findings suggested that sucrose might play a dual role of energy and signal in the occurrence of branch-thorns. Higher sucrose supply in apical buds from more leaves promoted the occurrence of branch-thorns via a lower content of T6P and higher expression levels of SUS, TPP and TPS, whereas fewer leaves inhibited the occurrence. The molecular hypothesis model of the leaf number/sucrose supply regulating the occurrence of branch-thorns in L. ruthenicum was established in the study, which provides foundation for breeding both Thless L. ruthenicum and Thless types of other species.

Pharmacodynamic studies of everolimus and sapanisertib treated PDX-PNETs using Western blot analysis of mTOR pathway targets.

Patients with pancreatic neuroendocrine tumors (PNET) commonly develop advanced disease and require systemic therapy. However, treatment options remain limited, in part, because experimental models that reliably emulate PNET disease are lacking. We therefore developed a patient-derived xenograft model of PNET (PDX-PNET), which we then used to evaluate two mTOR inhibitor drugs: FDA-approved everolimus and the investigational new drug sapanisertib. PDX-PNETs maintained a PNET morphology and PNET-specific gene expression signature with serial passage. PDX-PNETs also harbored mutations in genes previously associated with PNETs (such as MEN1 and PTEN), displayed activation of the mTOR pathway, and could be detected by Gallium-68 DOTATATE PET-CT. Treatment of PDX-PNETs with either everolimus or sapanisertib strongly inhibited growth. As seen in patients, some PDX-PNETs developed resistance to everolimus. However, sapanisertib, a more potent inhibitor of the mTOR pathway, caused tumor shrinkage in most everolimus-resistant tumors. Our PDX-PNET model is the first available, validated PDX model for PNET, and preclinical data from the use of this model suggest that sapanisertib may be an effective new treatment option for patients with PNET or everolimus-resistant PNET.