Search

Introduction:: Accurate identification of pulmonary arterial hypertension (PAH) in primary care and rural areas can be a challenging task. However, recent advancements in computer vision offer the potential for automated systems to detect PAH from echocardiography. Objectives:: Our aim was to develop a precise and efficient diagnostic model for PAH tailored to the unique requirements of intelligent diagnosis, especially in challenging locales like high-altitude regions. Methods:: We proposed the Chamber Attention Network (CAN) for PAH identification from echocardiographic images, trained on a dataset comprising 13,912 individual subjects. A convolutional neural network (CNN) for view classification was used to select the clinically relevant apical four chamber (A4C) and parasternal long axis (PLAX) views for PAH diagnosis. To assess the importance of different heart chambers in PAH diagnosis, we developed a novel Chamber Attention Module. Results:: The experimental results demonstrated that: 1) The substantial correspondence between our obtained chamber attention vector and clinical expertise suggested that our model was highly interpretable, potentially uncovering diagnostic insights overlooked by the clinical community. 2) The proposed CAN model exhibited superior image-level accuracy and faster convergence on the internal validation dataset compared to the other four models. Furthermore, our CAN model outperformed the others on the external test dataset, with image-level accuracies of 82.53% and 83.32% for A4C and PLAX, respectively. 3) Implementation of the voting strategy notably enhanced the positive predictive value (PPV) and negative predictive value (NPV) of individual-level classification results, enhancing the reliability of our classification outcomes. Conclusions:: These findings indicate that CAN is a feasible technique for AI-assisted PAH diagnosis, providing new insights into cardiac structural changes observed in echocardiography.

Abstract While the monolayer sheet is well-established as a Mott-insulator with a finite energy gap, the insulating nature of bulk 1T-TaS2 crystals remains ambiguous due to their varying dimensionalities and alterable interlayer coupling. In this study, we present a unique approach to unlock the intertwined two-dimensional Mott-insulator and three-dimensional band-insulator states in bulk 1T-TaS2 crystals by structuring a laddering stack along the out-of-plane direction. Through modulating the interlayer coupling, the insulating nature can be switched between band-insulator and Mott-insulator mechanisms. Our findings demonstrate the duality of insulating nature in 1T-TaS2 crystals. By manipulating the translational degree of freedom in layered crystals, our discovery presents a promising strategy for exploring fascinating physics, independent of their dimensionality, thereby offering a “three-dimensional” control for the era of slidetronics.

ObjectiveResearch evidence suggests that exercise is a potent therapeutic strategy for non-alcoholic fatty liver disease (NAFLD). Many investigations have delved into the curative potential of diverse exercise regimens on NAFLD. This investigation synthesizes findings from randomized controlled trials via a network meta-analysis to evaluate the efficacy of exercise-based interventions on NAFLD.MethodsWe conducted a search across five electronic databases (Web of Science, EMBASE, PubMed, SCOPUS, and CNKI)to identify randomized controlled trials (RCTs) comparing the effects of different exercise modalities on metabolic profiles and liver functions in patients with NAFLD. The literature search was comprehensive up to 15, December 2023. The selected studies were subjected to a rigorous quality appraisal and risk of bias analysis in accordance with the Cochrane Handbook’s guidelines, version 5.1.0. We employed Stata/MP 17 for the network meta-analysis, presenting effect sizes as standardized mean differences (SMD).ResultsThis study aggregated results from 28 studies, involving a total of 1,606 participants. The network meta-analysis revealed that aerobic exercise was the most effective intervention for improving BMI in patients with NAFLD, demonstrating a significant decrease in BMI (−0.72, 95%CI: −0.98 to −0.46; p < 0.05; Surface Under the Cumulative Ranking (SUCRA) = 79.8%). HIIT was the top intervention for enhancing HDL-C (0.12, 95% CI: 0.04 to 0.20; p < 0.05; SUCRA = 76.1%). Resistance exercise was the most effective for reducing LDL-C (−0.20, 95% CI: −0.33 to −0.06; p < 0.05; SUCRA = 69.7%). Mind-body exercise showed superior effectiveness in improving TC (−0.67, 95% CI: −1.10 to −0.24; p < 0.05; SUCRA = 89.7%), TG = −0.67, 95% CI: −1.10 to −0.24; p < 0.05; SUCRA = 99.6%), AST (−8.07, 95% CI: −12.88 to −3.25; p < 0.05; SUCRA = 76.1%), ALT (−12.56, 95% CI: −17.54 to −7.58; p < 0.05; SUCRA = 99.5%), and GGT (−13.77, 95% CI: −22.00 to −5.54; p < 0.05; SUCRA = 81.8%).ConclusionThis network meta-analysis demonstrates that exercise interventions positively affect various metabolic profiles and liver functions in NAFLD patients. Mind-body exercises are particularly effective, surpassing other exercise forms in improving metabolic profiles and liver functions.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier registration number CRD42024526332.

Pain sensitivity varies depending on both the state and age of an individual. For example, chronic pain is more common in older individuals, but the underlying mechanisms remain unknown. This study revealed that 18-month-old mice (aged) experienced more severe and long-lasting allodynia and hyperalgesia in the chronic constriction injury (CCI)-induced pain state compared to 2-month-old mice. Interestingly, the aged mice had a higher baseline mechanical pain threshold than the adult mice. The expression of spinal receptor-active modification protein 1 (RAMP1), as a key component and regulator of the calcitonin gene-related peptide (CGRP) receptor for nociceptive transmission from the periphery to the spinal cord, was reduced in the physiological state but significantly increased after CCI in the aged mice compared to the adult mice. Moreover, when RAMP1 was knocked down using shRNA, the pain sensitivity of adult mice decreased significantly, and CCI-induced allodynia in aged mice was reduced. These findings suggest that spinal RAMP1 is involved in regulating pain sensitivity in a state- and age-dependent manner. Additionally, interfering with RAMP1 could be a promising strategy for alleviating chronic pain in older individuals.

BackgroundThere is a growing interest in the use of complementary therapies for the prevention of disease and the maintenance of health. Furthermore, complementary therapies that incorporate exercise are becoming increasingly prevalent among the older adult, and thus may represent a crucial strategy for the primary and secondary prevention of cardiovascular disease (CVD). Exercise therapy, as a means to prevent and treat cardiovascular diseases, has been gradually applied in clinical practice. It has the advantages of reducing mortality, improving clinical symptoms, restoring physical function and improving quality of life. In recent years, traditional Chinese sports such as Ba Duan Jin and Qigong have developed rapidly. Therefore, a comprehensive systematic review is required to examine interventions involving Ba Duan Jin exercise in healthy adults or those at increased risk of CVD in order to determine the effectiveness of Ba Duan Jin exercise for the primary prevention of CVD.ObjectiveTo investigate the effect of Ba Duan Jin exercise intervention for the primary prevention of cardiovascular diseases.MethodsEight databases were systematically searched from inception to July, 2024 for randomized controlled trials (RCTs) to evaluated the impact of Ba Duan Jin exercise intervention on cardiovascular diseases. The search terms were “Cardiovascular diseases” “Ba Duan Jin” and “Randomized controlled.” The Cochrane risk assessment tool was used to evaluate the study quality, and the meta-analysis was performed using Rev. Man 5.4 software.ResultsSeventeen completed trials were conducted with 1,755 participants who were randomly assigned and met the inclusion criteria. All 17 studies were conducted in China. The meta-analysis indicates that Ba Duan Jin exercise therapy can provide long-term benefits (20–30 years) by reducing all-cause mortality (RR = 0.55, 95% CI: 0.44–0.68, p

The dispersion of reinforced particles is crucial in improving the mechanical properties of ceramic particles reinforced Al matrix composites. In this work, a novel interfacial projection strategy was proposed to improve the dispersion of TiB2 particles in Al-Si composites through high-throughput first-principles calculations with the experimental verification. Firstly, the Al(111)/TiB2(0001) interface model was constructed. Then, the pre-substitution of Si at 2 at. % concentration was employed to simulate the solutionized Al matrix. Secondly, alloying behaviors of 55 elements (10 substitution sites per element) in the Si-Al(111)/TiB2(0001) interface were studied by high-throughput first-principles calculations in terms of the relative interface formation energy and the relative work of adhesion. With these values, a theoretical alloying map for evaluating the dispersion ability of these alloying elements was plotted. Accordingly, the copper mold experiments were conducted to validate the theoretical alloying map. Based on the electron analysis, the enhanced interface bonds by alloying primarily attributed to electron accumulations around Si atom, indicating that the pre-substitution Si atom was vital for a reliable simulation result. Generally, this interfacial projection strategy provides a precise and potent approach in designing high-performance Al matrix composites, and should be applicable to other reinforced particles.

In this work, the (10 wt%, 30 wt%, 50 wt%) TiC reinforced AlFeCrCo medium entropy alloy (MEA) lightweight composite coatings with the extremely low porosity were successfully fabricated on Mg alloy substrate by resistance seam processing. The results showed that the microstructure of composite coating was consisting of a BCC-based MEA matrix and TiC particles, and a good metallurgical bonding with a semi-coherent relationship was formed between the coating and Mg alloy. Furthermore, the lightweight composite coatings (5.6–6.5 g cm−3) showed improved corrosion resistance over Mg alloy substrate. Specifically, the composite coatings exhibited optimized wear performance in the dry, deionized water and 3.5 wt% NaCl solution conditions with the increasing TiC content, surpassing related high/medium entropy alloy coatings, which is attributed to the formation of a coherent interface between the MEA matrix and the TiC particles. The first-principles calculations were performed to elucidate the nature for the higher bonding strength of TiC/MEA interface. In these wear conditions, the main wear mechanisms of composite coatings were discussed in terms of adhesive wear, oxidative wear and/or corrosive wear, in connection with their microstructure features and electrochemical behaviors. Based on the elevated anti-corrosion ability, this work has provided a strategy to fabricate advanced coatings on Mg alloys endowing with lower density, interfacial metallurgical bonding and optimized wear resistance, substantially contributing to the development of high-performance composite coatings.

Abstract The metastasis of non-small cell lung cancer (NSCLC) is the leading death cause of NSCLC patients, which requires new biomarkers for precise diagnosis and treatment. Circular RNAs (circRNAs), the novel noncoding RNA, participate in the progression of various cancers as microRNA or protein sponges. We revealed the mechanism by which circEPB41L2 (hsa_circ_0077837) blocks the aerobic glycolysis, progression and metastasis of NSCLC through modulating protein metabolism of PTBP1 by the E3 ubiquitin ligase TRIP12. With ribosomal RNA-depleted RNA seq, 57 upregulated and 327 downregulated circRNAs were identified in LUAD tissues. circEPB41L2 was selected due to its dramatically reduced levels in NSCLC tissues and NSCLC cells. Interestingly, circEPB41L2 blocked glucose uptake, lactate production, NSCLC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, acting as a scaffold, circEPB41L2 bound to the RRM1 domain of the PTBP1 and the E3 ubiquitin ligase TRIP12 to promote TRIP12-mediated PTBP1 polyubiquitylation and degradation, which could be reversed by the HECT domain mutation of TRIP12 and circEPB41L2 depletion. As a result, circEPB41L2-induced PTBP1 inhibition led to PTBP1-induced PKM2 and Vimentin activation but PKM1 and E-cadherin inactivation. These findings highlight the circEPB41L2-dependent mechanism that modulates the “Warburg Effect” and EMT to inhibit NSCLC development and metastasis, offering an inhibitory target for NSCLC treatment.

Abstract Background Cancer and coronary artery disease (CAD) is reported to often co-exist in same individuals, however, whether cancer is directly associated with anatomical severity of CAD is rarely studied. The present study aimed to observe the relationship between newly diagnosed cancer and anatomical severity of CAD, moreover, to investigate effect of inflammation on the relationship of cancer with CAD. Methods 374 patients with newly diagnosed cancer who underwent coronary angiography (CAG) were enrolled. Through 1:3 propensity score matching (PSM) to cancer patients based on the age and gender among 51,106 non-cancer patients who underwent CAG, 1122 non-cancer patients were selected as control patients. Anatomical severity of CAD was assessed using SYNTAX score (SXscore) based on coronary angiographic image. SXscore ≤ 22 (highest quartile) was defined as SX-low, and SXscore > 22 as SX-high. The ratio of neutrophil to lymphocyte count (NLR) was used to describe inflammation level. Association between cancer and the anatomical severity of CAD was investigated using logistic regression. Results Univariate logistic regression analysis showed a correlation between cancer and anatomical severity of CAD (OR: 1.419, 95% CI: 1.083–1.859; P = 0.011). Cancer was associated with increased risk of SX-high after adjusted for common risk factors of CAD (OR: 1.598, 95% CI: 1.172–2.179, P = 0.003). Significant association between cancer and SX-high was revealed among patients with high inflammation (OR: 1.656, 95% CI: 1.099–2.497, P = 0.016), but not among patients with low inflammation (OR: 1.530, 95% CI: 0.973–2.498, P = 0.089). Conclusions Cancer was associated with severity of CAD, however, the association between the two diseases was significant among patients with high inflammation rather than among patients with low inflammation.

Exceptional ductility has been a long-sought-after property of metallic glasses, and cryogenic thermal cycling rejuvenation has been actively explored to enhance the plasticity of metallic glasses. By tuning the holding time and number of cycles of cryogenic thermal cycling processing, we here report a (Zr0.8125Cu0.1875)79Ni10Al10Nb1 metallic glass of peak rejuvenation with the plasticity of an order of magnitude higher than that of the as-cast glass, without sacrificing its strength. Characterizations indicate that the loose atomic packing of the metallic glass of peak rejuvenation facilitates the generation and proliferation of shear bands in the early stage of plastic deformation, and the resultant dense shear bands tend to be deflected due to their interaction with each other and/or structural inhomogeneity in the matrix, hindering their rapid propagation and in turn increasing the plasticity. The combination of high relaxation enthalpy and high plasticity obtained here is outstanding from the previous rejuvenated metallic glasses which have either high relaxation enthalpy or high plasticity, while never both. This work identifies an alloy system with very high efficiency in plasticity improvement through cryogenic thermal cycling rejuvenation and represents a promising guide for improving the plasticity of metallic glasses.

Due to the transboundary nature of air pollutants, a province's efforts to improve air quality can reduce PM2.5 concentration in the surrounding area. The inter-provincial PM2.5 pollution transport could bring great challenges to related environmental management work, such as financial fund allocation and subsidy policy formulation. Herein, we examined the transport characteristics of PM2.5 pollution across provinces in 2013 and 2020 via chemical transport modeling and then monetized inter-provincial contributions of PM2.5 improvement based on pollutant emission control costs. We found that approximately 60% of the PM2.5 pollution was from local sources, while the remaining 40% originated from outside provinces. Furthermore, about 1011 billion RMB of provincial air pollutant abatement costs contributed to the PM2.5 concentration decline in other provinces during 2013–2020, accounting for 41.2% of the total abatement costs. Provinces with lower unit improvement costs for PM2.5, such as Jiangsu, Hebei, and Shandong, were major contributors, while Guangdong, Guangxi, and Fujian, bearing higher unit costs, were among the main beneficiaries. Our study identifies provinces that contribute to air quality improvement in other provinces, have high economic efficiency, and provide a quantitative framework for determining inter-provincial compensations. This study also reveals the uneven distribution of pollution abatement costs (PM2.5 improvement/abatement costs) due to transboundary PM2.5 transport, calling for adopting inter-provincial economic compensation policies. Such mechanisms ensure equitable cost-sharing and effective regional air quality management.

Background and objectivesAcute mountain sickness (AMS) is a pathology with different symptoms in which the organism is not adapted to the environment that occurs under the special environment of high altitude. Its main mechanism is the organism’s tissue damage caused by acute hypobaric hypoxia. Traditional Chinese medicine (TCM) theory focuses on the holistic concept. TCM has made remarkable achievements in the treatment of many mountain sicknesses. This review outlines the pathogenesis of AMS in modern and traditional medicine, the progress of animal models of AMS, and summarizes the therapeutic effects of TCM on AMS.MethodsUsing the keywords “traditional Chinese medicine,” “herbal medicine,” “acute mountain sickness,” “high-altitude pulmonary edema,” “high-altitude cerebral edema,” “acute hypobaric hypoxia,” and “high-altitude,” all relevant TCM literature published up to November 2023 were collected from Scopus, Web of Science, PubMed, and China National Knowledge Infrastructure databases, and the key information was analyzed.ResultsWe systematically summarised the effects of acute hypobaric hypoxia on the tissues of the organism, the study of the methodology for the establishment of an animal model of AMS, and retrieved 18 proprietary Chinese medicines for the clinical treatment of AMS. The therapeutic principle of medicines is mainly invigorating qi, activating blood and removing stasis. The components of botanical drugs mainly include salidroside, ginsenoside Rg1, and tetrahydrocurcumin. The mechanism of action of TCM in the treatment of AMS is mainly through the regulation of HIF-1α/NF-κB signaling pathway, inhibition of inflammatory response and oxidative stress, and enhancement of energy metabolism.ConclusionThe main pathogenesis of AMS is unclear. Still, TCM formulas and components have been used to treat AMS through multifaceted interventions, such as compound danshen drip pills, Huangqi Baihe granules, salidroside, and ginsenoside Rg1. These components generally exert anti-AMS pharmacological effects by inhibiting the expression of VEGF, concentration of MDA and pro-inflammatory factors, down-regulating NF-κB/NLRP3 pathway, and promoting SOD and Na + -K + -ATPase activities, which attenuates acute hypobaric hypoxia-induced tissue injury. This review comprehensively analyses the application of TCM in AMS and makes suggestions for more in-depth studies in the future, aiming to provide some ideas and insights for subsequent studies.

BackgroundPlateau environment may pose a serious impact on the physiological and psychological stress of people stationed on a plateau, especially for those engaged in military training and occupational activities. There is an urgent need to find drugs to prevent and treat injuries caused by high-altitude environment. ObjectiveTo analyze the current status, hotspots, and future trends of domestic and international research in the field of prevention and treatment of high-altitude disease (HAD) by traditional Chinese medicine (TCM), and provide references for scientific research. MethodsWeb of Science Core Collection (WOSCC) and China National Knowledge Infrastructure (CNKI) were searched for literature on TCM and HAD published from inception to 2022. Excel, CiteSpace, VOSviewer, and RStudio softwares were used to conduct visual analysis on the number of publications, types of publications, journals, authors, research institutions, and keywords. ResultsA total of 501 publications were evaluated in the present study, including 443 Chinese publications and 58 English publications. The annual number of publications showed a rising trend. MA Huiping was the leading author in number of publications in Chinese (37 publications), and ZHANG Yi and MENG Xianli were the leading authors in the number of publications in English (both 8 publications), respectively. The institutions with the most publications in Chinese were The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army and Lanzhou General Hospital of Lanzhou Military Region (both 32 publications), and the institution with the most publications in English was Chengdu University of Traditional Chinese Medicine (8 publications), respectively. The Chinese and English journals with the largest number of publications were the Journal of High Altitude Medicine (39 publications) and the Journal of Ethnopharmacology (10 publications), respectively. The most highly cited Chinese and English literature included Effects of rhodiola on the free radical metabolism and serum creatine kinase after exercise at plateau (61 citations) and Anti-hypoxic activity at simulated high altitude was isolated in petroleum ether extract of Saussurea involucrate (68 citations) , respectively. The most frequent keywords in the Chinese and English literature were high altitude polycythemia and oxidative stress, respectively. The keyword time zone and emergence maps showed that the research hotspots in this field shifted from prevention and treatment of HAD to animal experiments, and then to mechanisms of action, in which oxidative stress, hypoxic injury, inflammation, and apoptosis were the main focuses. ConclusionThe research of TCM against HAD is identified from early clinical observation to associations between clinical outcome variation and pharmacological mechanisms, and further to applying multi-omics techniques to explore the physical basis of TCM efficacy and mechanisms of action with focuses like TCM formula and single herb active ingredients, so as to elaborate potential scientific connotation of TCM against HAD.

This study aimed to enhance the mechanical properties of high pressure die casting (HPDC) Al9Si0.6Mn alloys by incorporating in-situ TiB2 particles. The effects of TiB2 addition on the microstructure and mechanical properties of as-HPDC Al9Si0.6Mn alloys were investigated. The results showed that TiB2 addition refined the bimodal grain structure and eutectic Si morphology in the central region of the as-HPDC alloys, which was the primary contributor to the mechanical properties. The thickness of the skin region and band zone increased with increasing TiB2 addition, while the central region exhibited a reduced thickness but remained dominant on the entire cross-section. The optimal TiB2 content was found to be 1 wt%, resulting in the 23.4 % reduction in grain size and 10.7 % enhancement in yield strength. The modified strengthening model based on the microstructure features of the central region accurately predicted the yield strengths of as-HPDC alloys. Finally, the morphological strengthening factors induced by TiB2 particles were analytically illustrated in the HPDC Al9Si0.6Mn–TiB2 alloys.

Monkeypox virus (MPXV) is a cross-kingdom pathogen infecting both humans and wildlife, which poses a significant health risk to the public. Although MPXV attracts broad attention, there is a lack of adequate studies to elucidate pathogenic mechanisms associated with viral infections. In this study, a high-throughput RNA sequencing (RNA-seq) and liquid chromatography–tandem mass spectrometry (LC-MS/MS) approach was used to explore the transcriptional and metabolic responses of MPXV A23 protein to HEK293T cells. The protein–protein interactions and signaling pathways were conducted by GO and KEGG analyses. The localization of A23 protein in HEK293T cells was detected by immunofluorescence. A total of 648 differentially expressed genes (DEGs) were identified in cells by RNA-Seq, including 314 upregulated genes and 334 downregulated genes. Additionally, liquid chromatography–tandem mass spectrometry (LC-MS/MS) detected 115 cellular proteins that interact with the A23 proteins. Transcriptomic sequencing analysis revealed that transfection of MPXV A23 protein modulated genes primarily associated with cellular apoptosis and DNA damage repair. Proteomic analysis indicated that this protein primarily interacted with host ribosomal proteins and histones. Following the identification of the nuclear localization sequence RKKR within the A23 protein, a truncated mutant A23ΔRKKR was constructed to investigate the subcellular localization of A23 protein. The wild-type A23 protein exhibits a significantly higher nuclear-to-cytoplasmic ratio, exceeding 1.5, in contrast to the mutant A23ΔRKKR, which has a ratio of approximately 1. Immunofluorescence assays showed that the A23 protein was mainly localized in the nucleus. The integration of transcriptomics and proteomics analysis provides a comprehensive understanding of the interaction between MPXV A23 protein and the host. Our findings highlight the potential role of this enzyme in suppressing host antiviral immune responses and modulating host gene expression.

Abstract Background Okur‐Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual disability, developmental delay, and multisystemic abnormalities. Methods We performed the whole‐exome sequencing for a patient in a Chinese family. The co‐segregation study using the Sanger sequencing method was performed among family members. Reverse transcription and quantitative real‐time polymerase chain reaction were carried out using total RNA from blood samples of the proband and wild‐type control subjects. A review of patients with OCNDS harboring CSNK2A1 pathogenic variants was conducted through a comprehensive search of the PubMed database. Results We identified a novel CSNK2A1 frameshift variant p.Tyr323Leufs*16 in a Chinese family. The proband, a 31‐year‐old female, presented with abnormal eating habits, recurrent seizures, language impairment, and intellectual disability. Her mother exhibited postnatal hernias, splenomegaly, and a predisposition to infections, but showed no significant developmental impairments or intellectual disability. Genetic studies revealed the presence of this variant in CSNK2A1 in both the proband and her mother. Transcription analysis revealed this variant may lead to nonsense‐mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism. We reviewed 47 previously reported OCNDS cases and discovered that individuals carrying CSNK2A1 null variants may exhibit a diminished frequency of symptoms linked to language deficits, dysmorphic facial features, or intellectual disability, consequently presenting an overall milder phenotype when compared to those with missense variants. Conclusion We report a novel frameshift variant, p.Tyr323Leufs*16, in an OCNDS family with a generally mild phenotype. This study may broaden the spectrum of clinical presentations associated with OCNDS and contribute novel insights into the genotype–phenotype correlation of this condition.

BackgroundMonkeypox or mpox virus (mpox) is a double-stranded DNA virus that poses a significant threat to global public health security. The F3 protein, encoded by mpox, is an apoenzyme believed to possess a double-stranded RNA-binding domain (dsRBD). However, limited research has been conducted on its function. In this study, we present data on the transcriptomics and proteomics of F3L-transfected HEK293T cells, aiming to enhance our comprehension of F3L.MethodsThe gene expression profiles of pCAGGS-HA-F3L transfected HEK293T cells were analyzed using RNA-seq. Proteomics was used to identify and study proteins that interact with F3L. Real-time PCR was used to detect mRNA levels of several differentially expressed genes (DEGs) in HEK293T cells (or Vero cells) after the expression of F3 protein.ResultsA total of 14,822 genes were obtained in cells by RNA-Seq and 1,672 DEGs were identified, including 1,156 up-regulated genes and 516 down-regulated genes. A total of 27 cellular proteins interacting with F3 proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and 19 cellular proteins with large differences in abundance ratios were considered to be candidate cellular proteins. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the DEGs were significantly enriched in immune-related pathways, including type I interferon signaling pathway, response to virus, RIG-I-like receptor signaling pathway, NOD-like receptor signaling pathway, etc. Moreover, some selected DEGs were further confirmed by real-time PCR and the results were consistent with the transcriptome data. Proteomics data show that cellular proteins interacting with F3 proteins are mainly related to RNA splicing and protein translation.ConclusionsOur analysis of transcriptomic and proteomic data showed that (1) F3L up-regulates the transcript levels of key genes in the innate immune signaling pathway, such as RIGI, MDA5, IRF5, IRF7, IRF9, ISG15, IFNA14, and elicits a broad spectrum of antiviral immune responses in the host. F3L also increases the expression of the FOS and JNK genes while decreasing the expression of TNFR2, these factors may ultimately induce apoptosis. (2) F3 protein interacts with host proteins involved in RNA splicing and protein translation, such as SNRNP70, POLR2H, HNRNPA1, DDX17, etc. The findings of this study shed light on the function of the F3 protein.

The root system plays a decisive role in the growth and development of plants. The water requirement of a root system depends strongly on the plant species. Potatoes are an important food and vegetable crop grown worldwide, especially under irrigation in arid and semi-arid regions. However, the expected impact of global warming on potato yields calls for an investigation of genes related to root development and drought resistance signaling pathways in potatoes. In this study, we investigated the molecular mechanisms of different drought-tolerant potato root systems in response to drought stress under controlled water conditions, using potato as a model. We analyzed the transcriptome and proteome of the drought-sensitive potato cultivar Atlantic (Atl) and the drought-tolerant cultivar Qingshu 9 (Q9) under normal irrigation (CK) and weekly drought stress (D). The results showed that a total of 14,113 differentially expressed genes (DEGs) and 5596 differentially expressed proteins (DEPs) were identified in the cultivars. A heat map analysis of DEGs and DEPs showed that the same genes and proteins in Atl and Q9 exhibited different expression patterns under drought stress. Weighted gene correlation network analysis (WGCNA) showed that in Atl, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG)-enriched pathways were related to pyruvate metabolism and glycolysis, as well as cellular signaling and ion transmembrane transporter protein activity. However, GO terms and KEGG-enriched pathways related to phytohormone signaling and the tricarboxylic acid cycle were predominantly enriched in Q9. The present study provides a unique genetic resource to effectively explore the functional genes and uncover the molecular regulatory mechanism of the potato root system in response to drought stress.

Abstract Background Recent studies have demonstrated that glioma-associated mesenchymal stem cells (GA-MSCs) are implicated in the regulation of glioma malignant progression. However, the prognostic value of GA-MSCs has not been comprehensively explored in glioma. Methods We extracted GA-MSCs from glioma tissues, established intracranial xenograft models in nude mice, and obtained GA-MSC-related genes (GA-MSCRGs) by using microarrays. The transcriptome data and clinical information of glioma patients were obtained from the CGGA and TCGA databases. We screened 8 prognostic GA-MSCRGs to construct a prognostic index by using the multivariate Cox regression method. The validity of the GA-MSCRGPI was verified in the training (CGGA693) and validation (TCGA and CGGA325) cohorts. The expression patterns of these 8 GA-MSCRGs were validated in 78 glioma tissue specimens by using a qRT‒PCR assay. Results GA-MSCs were successfully isolated from glioma tissues. Based on intracranial xenograft models and transcriptome microarray screening, 8 genes (MCM7, CDK6, ORC1, CCL20, TNFRSF12A, POLA1, TRAF1 and TIAM1) were selected for the construction of a GA-MSC-related gene prognostic index (GA-MSCRGPI). In both the training and validation cohorts, high GA-MSCRGPI patients showed an inferior survival outcome compared with low GA-MSCRGPI patients. A nomogram was established based on independent prognostic indicators (age, WHO grade and GA-MSCRGPI) and exhibited a strong forecasting ability for overall survival (OS). Moreover, we found that the GA-MSCRGPI could evaluate the prognosis of glioma patients undergoing chemoradiotherapy. The high GA-MSCRGPI group exhibited higher immune, stromal and ESTIMATE scores; lower tumor purity; higher infiltration of Tregs and M2-type macrophages; fewer activated NK cells; and higher expression of immune checkpoints. Tumor Immune Dysfunction and Exclusion (TIDE) showed that the high GA-MSCRGPI group had more responders to ICI therapy. The results of the genetic mutation profile and tumor mutation burden (TMB) in different GA-MSCRGPI subgroups further supplement GA-MSCRGPI-related mechanisms. Finally, the expression patterns of 8 selected GA-MSCRGs in GA-MSCRGPI were correlated with glioma WHO grades to a certain extent. Conclusion The constructed GA-MSCRGPI could predict prognosis and guide individualized therapy in glioma patients.

Objectives: Knowledge graphs and ontologies in the biomedical domain provide rich contextual knowledge for a variety of challenges. Employing that for knowledge-driven NLP tasks such as gene-disease association prediction represents a promising way to increase the predictive power of a model. Methods: We investigated the power of infusing the embedding of two aligned ontologies as prior knowledge to the NLP models. We evaluated the performance of different models on some large-scale gene-disease association datasets and compared it with a model without incorporating contextualized knowledge (BERT). Results: The experiments demonstrated that the knowledge-infused model slightly outperforms BERT by creating a small number of bridges. Thus, indicating that incorporating cross-references across ontologies can enhance the performance of base models without the need for more complex and costly training. However, further research is needed to explore the generalizability of the model. We expected that adding more bridges would bring further improvement based on the trend we observed in the experiments. In addition, the use of state-of-the-art knowledge graph embedding methods on a joint graph from connecting OGG and DOID with bridges also yielded promising results. Conclusion: Our work shows that allowing language models to leverage structured knowledge from ontologies does come with clear advantages in the performance. Besides, the annotation stage brought out in this paper is constrained in reasonable complexity.

Abstract Background Neuroinflammation plays a significant role in the progression of frontotemporal dementia (FTD). However, the association between peripheral inflammatory factors and brain neurodegeneration is poorly understood. We aimed to examine changes in peripheral inflammatory markers in patients with behavioural variant FTD (bvFTD) and explore the potential association between peripheral inflammation and brain structure, metabolism, and clinical parameters. Methods Thirty-nine bvFTD patients and 40 healthy controls were enrolled and underwent assessment of plasma inflammatory factors, positron emission tomography/magnetic resonance imaging, and neuropsychological assessments. Group differences were tested using Student’s t test, Mann‒Whitney U test, or ANOVA. Partial correlation analysis and multivariable regression analysis were implemented using age and sex as covariates to explore the association between peripheral inflammatory markers, neuroimaging, and clinical measures. The false discovery rate was used to correct for the multiple correlation test. Results Plasma levels of six factors, including interleukin (IL)-2, IL-12p70, IL-17A, tumour necrosis superfamily member 13B (TNFSF/BAFF), TNFSF12 (TWEAK), and TNFRSF8 (sCD30), were increased in the bvFTD group. Five factors were significantly associated with central degeneration, including IL-2, IL-12p70, IL-17A, sCD30/TNFRSF8, and tumour necrosis factor (TNF)-α; the association between inflammation and brain atrophy was mainly distributed in frontal–limbic–striatal brain regions, whereas the association with brain metabolism was mainly in the frontal–temporal–limbic–striatal regions. BAFF/TNFSF13B, IL-4, IL-6, IL-17A and TNF-α were found to correlate with clinical measures. Conclusion Peripheral inflammation disturbance in patients with bvFTD participates in disease-specific pathophysiological mechanisms, which could be a promising target for diagnosis, treatment, and monitoring therapeutic efficacy.

Although the fusion of multispectral (MS) and hyperspectral (HS) images in remote sensing has become relatively mature, and different types of fusion methods have their own characteristics in terms of fusion effect, data dependency, and computational efficiency, few studies have focused on the impact of radiance extreme areas, which widely exist in real remotely sensed scenes. To this end, this paper proposed a novel method called radiance extreme area compensation fusion (RECF). Based on the architecture of spectral unmixing fusion, our method uses the reconstruction of error map to construct local smoothing constraints during unmixing and utilizes the nearest-neighbor multispectral data to achieve optimal replacement compensation, thereby eliminating the impact of overexposed and underexposed areas in hyperspectral data on the fusion effect. We compared the RECF method with 11 previous published methods on three sets of airborne hyperspectral datasets and HJ2 satellite hyperspectral data and quantitatively evaluated them using 5 metrics, including PSNR and SAM. On the test dataset with extreme radiance interference, the proposed RECF method achieved well in the overall evaluation results; for instance, the PSNR metric reached 47.6076 and SAM reached 0.5964 on the Xiong’an dataset. In addition, the result shows that our method also achieved better visual effects on both simulation and real datasets.

Peppers are a major vegetable crop worldwide. With the completion of additional genome assemblies, a multitude of single-nucleotide polymorphisms (SNPs) can be utilized for population structure and genetic diversity analysis. In this study, we used target SNP-sequencing as a new high-throughput sequencing technology, screening out 425 perfect SNPs for analyzing the genetic diversity and population structure among 496 pepper lines from five pepper species in China and abroad. The perfect SNP panel exhibited commendable discriminative ability, as indicated by the average values of polymorphism information content, observed heterozygosity, minor allele frequency, and genetic diversity, which were 0.346, 0.011, 0.371, and 0.449, respectively. Based on phylogenetic, population structure, and principal component analyses, 484 C. annuum lines were divided into four subpopulations according to the shape of fruit: blocky fruit, wide-horn fruit, narrow-horn fruit, and linear fruit. These subpopulations displayed clear clustering with minimal or no overlap. Moreover, F statistic (Fst) analysis revealed considerable distinctions among these subpopulations. Additionally, we established a set of 47 core SNPs that could effectively differentiate among all pepper lines. This core SNP set could precisely classify the C. annuum lines into four distinct fruit-shape groups. The blocky and narrow-horn fruit subpopulations displayed the lowest and highest genetic diversity, respectively. This study highlights the importance of fruit shape as a crucial trait in pepper breeding. Moreover, this work indicates the immense potential of optimized target SNP technology in the addition of foreground markers of important traits to improve molecular breeding efficiency, and demonstrates its broad application prospects in the genetic analysis and variety identification of peppers.

Monitoring animal activities help assess the effects of environmental conditions and anthropogenic factors on various species. Entomology-related monitoring methods based on radar, machine vision, and other technologies have developed rapidly in recent years. This research focuses on real-time, laser-based monitoring methods that enable online monitoring of insect activity and study the response of insect populations to changes in environmental conditions such as weather. We summarise four specific applications of monitoring insects based on various laser remote sensing techniques, including setting the electronic trap, collecting backscattered light or fluorescence from target insects in open space, and indirectly monitoring insect population activity by drawing forest canopy characteristics. We discuss the application opportunities of these methods and the challenges faced in practical monitoring and emphasise the trends and requirements for future research.

Abstract p53 is the most highly mutated tumor suppressor across multiple types of human cancers. The level and function of p53 are fine-tuned through multifaced mechanisms in which the protein–protein interaction between p53 and MDM2 is considered as a major circuit. Recent studies suggest therapeutic strategy attempts to restore p53 function by small molecule inhibitors targeting p53–MDM2 interaction can be a promising direction in treating cancers with wild-type or functional p53. Currently, clinical tests of the p53–MDM2 protein–protein interaction inhibitors (PPIs) are underway. However, it remains elusive about the biomarkers that may predict the therapeutic responses to those inhibitors. Here we report that RNA-binding protein LIN28B directly regulates p53 through binding to the 5′΄ untranslated region of p53 mRNA and blocks its translation by competing with a translation enhancer protein, ribosomal protein L26 (RPL26). This regulatory mechanism of LIN28B does not involve let-7 maturation or the canonical protein turnover pathway of p53. Furthermore, we show that inhibition of LIN28B unleashes the translational suppression of p53 through RPL26, and leads to enhanced sensitivities of cancer cells to inhibitors of p53–MDM2 interaction. Together, we demonstrate a competitive regulatory mechanism of p53 by LIN28B, which has important implications in developing biomarkers to the therapies aiming to reinstate p53 function.

Abstract Object detection is one of the main tasks of computer vision. Object detection algorithms usually rely on deep convolutional neural networks, which require the host device to have high computing capabilities, greatly limiting the application of object detection methods for mobile devices with limited computing capabilities, such as embedded devices. Among the current object detection algorithms, the you only look once (YOLO) series takes both speed and accuracy into consideration and is one of the most commonly used methods for object detection. In this article, TRC‐YOLO is proposed, which improves the mean average precision (mAP) and real‐time detection speed of the model while reducing the size of the model. In TRC‐YOLO, the convolution kernel of YOLO v4‐tiny is pruned and an expansive convolution layer is introduced into the residual module of the network to produce an hourglass Cross Stage Partial ResNet (CSPResNet) structure. A receptive field block (RFB) that simulates human vision is also added, increasing the receptive field of the model and strengthening the feature extraction ability of the network. In addition, the convolutional block attention module is applied, which combines spatial attention and channel attention, to enhance the effective features of the model and reduce the negative impact of noise on the model. The size of the TRC‐YOLO model is 17.8 MB, which is 5.9 MB smaller than YOLO v4‐tiny, and the model parameter is 2.983 billion floating point operations per second (BFLOP/s) (3.834 BFLOP/s less than YOLO v4‐tiny). In addition, TRC‐YOLO achieves a real‐time performance of 36.9 frames per second on a Jetson Xavier NX, and its mAP on the PASCAL VOC dataset is 66.4% (3.83% higher than YOLO v4‐tiny). In addition, the mAP of TRC‐YOLO on the MS COCO dataset is 37.7%, which is 1.9% higher than that of the baseline model.

The precise liquidus projection of the V-Ti-Fe system are crucial for designing high-performance hydrogen permeation alloys, but there are still many controversies in the research of this system. To this end, this article first uses the CALPHAD (CALculation of PHAse Diagrams) method to reconstruct the alloy phase diagram and compares and analyses existing experimental data, confirming that the newly constructed phase diagram in this article has good reliability and accuracy. Second, this obtained phase diagram was applied to the subsequent development process of hydrogen permeation alloys, and the (Ti65Fe35)100−xVx (x = 0, 2.5, 5, 10, 15, 25) alloys with dual-phase {bcc-(V, Ti) + TiFe} structure were successfully explored. In particular, the alloys with x values equal to 2.5 at.% and 5 at.% exhibit relatively high hydrogen permeability. Third, to further increase the H2 flux permeation through the alloys, a 500-mm-long tubular (Ti65Fe35)95V5 membrane for hydrogen permeation was prepared for the first time. Hydrogen permeation testing showed that this membrane had a very high H2 flux (4.06 mL min−1), which is ca. 6.7 times greater than the plate-like counterpart (0.61 mL min−1) under the same test conditions. This work not only indicates the reliability of the obtained V-Ti-Fe phase diagram in developing new hydrogen permeation alloys, but also demonstrates that preparing tubular membranes is one of the most important means of improving H2 flux.

At present, the V-Ti-Co phase diagram is not established, which seriously hinders the subsequent development of this potential hydrogen permeation alloy system. To this end, this article constructed the first phase diagram of the V-Ti-Co system by using the CALculation of PHAse Diagrams (CALPHAD) approach as well as relevant validation experiments. On this basis, hydrogen-permeable VxTi50Co50−x (x = 17.5, 20.5, …, 32.5) alloys were designed, and their microstructure characteristics and hydrogen transport behaviour were further studied by XRD, SEM, EDS, and so on. It was found that six ternary invariant reactions are located in the liquidus projection, and the phase diagram is divided into eight phase regions by their connecting lines. Among them, some alloys in the TiCo phase region were proven to be promising candidate materials for hydrogen permeation. Typically, VxTi50Co50−x (x = 17.5–23.5) alloys, which consist of the primary TiCo and the eutectic {bcc-(V, Ti) and TiCo} structure, show a high hydrogen permeability without hydrogen embrittlement. In particular, V23.5Ti50Co26.5 exhibit the highest permeability of 4.05 × 10−8 mol H2 m−1s−1Pa−0.5, which is the highest value known heretofore in the V-Ti-Co system. The high permeability of these alloys is due in large part to the simultaneous increment of hydrogen solubility and diffusivity, and is closely related to the composition of hydrogen permeable alloys, especially the Ti content in the (V, Ti) phase. The permeability of this alloy system is much higher than those of Nb-TiCo and/or Nb-TiNi alloys.

Northeast China plays a pivotal role in producing commodity grains. The precipitation and temperature distribution during the growth season is impacted by geographical and climate factors, rendering the region vulnerable to drought. However, relying on a single index does not reflect the severity and extent of drought in different regions. This research utilised the random forest (RF) model for screening remote sensing indices. Relative soil moisture (RSM) was employed to compare seven commonly used indices: the temperature vegetation dryness index (TVDI), vegetation supply water index (VSWI), vegetation condition index (VCI), temperature condition index (TCI), vegetation health index (VHI), multi-band drought index (MBDI), and normalised difference drought index (NDDI). The effectiveness of these indices for monitoring drought during different developmental stages of spring maize was evaluated. Trend rates were employed to investigate the temporal changes in drought patterns of spring maize from 2003 to 2020, and the Sen + Mann–Kendall test was used to analyse spatial variations. The results showed the following: (1) The seven remote sensing indices could accurately track drought during critical growth stages with the TVDI demonstrating higher applicability than the other six indices. (2) The application periods of two TVDIs with different parameters differed for the drought monitoring of spring maize in different developmental periods. The consistency and accuracy of the normalised difference vegetation index (NDVI)-based TVDI (TVDIN) were 5.77% and 34.62% higher than those of the enhanced vegetation index (EVI)-based TVDI (TVDIE), respectively, in the early stage. In contrast, the TVDIE exhibited 13.46% higher consistency than the TVDIN in the middle stage, and the accuracy was the same. During the later stage, the TVDIE showed significantly higher consistency and accuracy than the TVDIN with consistency increases of 9.61% and 38.64%, respectively. (3) The drought trend in northeast China increased from 2003 to 2020, exhibiting severe spring drought and a weakening of the drought in summer. The southern, southwestern, and northwestern parts of northeast China showed an upward drought trend; the drought-affected areas accounted for 37.91% of the study area. This paper identified the most suitable remote sensing indices for monitoring drought in different developmental stages of spring maize. The results provide a comprehensive understanding of the spatial–temporal patterns of drought during the past 18 years. These findings can be used to develop a dynamic agricultural drought monitoring model to ensure food security.

Drought stress is a major threat to sustainable crop production worldwide. Despite the positive role of calcium (Ca2+) in improving plant drought tolerance in different crops, little attention has been paid to its role in mitigating drought stress in potatoes. In the present study, we studied the effect of foliar chelated sugar alcohol calcium treatments on two potato cultivars with different drought responses applied 15 and 30 days after limiting soil moisture. The results showed that the foliar application of calcium treatments alleviated the SPAD chlorophyll loss of the drought-sensitive cultivar ‘Atlantic’ (Atl) and reduced the inhibition of photosynthetic parameters, leaf anatomy deformation, and MDA and H2O2 content of both cultivars under drought stress. The Ca2+ treatments changed the expression of several Calcium-Dependent Protein Kinase (StCDPK) genes involved in calcium sensing and signaling and significantly increased antioxidant enzyme activities, average tuber weight per plant, and tuber quality of both cultivars. We conclude that calcium spray treatments improved the drought tolerance of both potato cultivars and were especially effective for the drought-sensitive cultivar. The present work suggests that the foliar application of calcium is a promising strategy to improve commercial potato yields and the economic efficiency of potato production under drought stress conditions.

Potato is one of the most important vegetable crops worldwide. Its growth, development and ultimately yield is hindered by drought stress condition. Breeding and selection of deep-rooted and drought-tolerant potato varieties has become a prime approach for improving the yield and quality of potato (Solanum tuberosum L.) in arid and semiarid areas. A comprehensive understanding of root development-related genes has enabled scientists to formulate strategies to incorporate them into breeding to improve complex agronomic traits and provide opportunities for the development of stress tolerant germplasm. Root response to drought stress is an intricate process regulated through complex transcriptional regulatory network. To understand the rooting depth and molecular mechanism, regulating root response to drought stress in potato, transcriptome dynamics of roots at different stages of drought stress were analyzed in deep (C119) and shallow-rooted (C16) cultivars. Stage-specific expression was observed for a significant proportion of genes in each cultivar and it was inferred that as compared to C16 (shallow-rooted), approximately half of the genes were differentially expressed in deep-rooted cultivar (C119). In C16 and C119, 11 and 14 coexpressed gene modules, respectively, were significantly associated with physiological traits under drought stress. In a comparative analysis, some modules were different between the two cultivars and were associated with differential response to specific drought stress stage. Transcriptional regulatory networks were constructed, and key components determining rooting depth were identified. Through the results, we found that rooting depth (shallow vs deep) was largely determined by plant-type, cell wall organization or biogenesis, hemicellulose metabolic process, and polysaccharide metabolic process. In addition, candidate genes responding to drought stress were identified in deep (C119) and shallow (C16) rooted potato varieties. The results of this study will be a valuable source for further investigations on the role of candidate gene(s) that affect rooting depth and drought tolerance mechanisms in potato.

The second messenger calcium (Ca2+) is a ubiquitous intracellular signaling molecule found in eukaryotic cells. In plants, the multigene family of calcium-dependent protein kinases (CDPKs) plays an important role in regulating plant growth, development, and stress tolerance. CDPKs sense changes in intracellular Ca2+ concentration and translate them into phosphorylation events that initiate downstream signaling processes. Several functional and expression studies on different CDPKs and their encoding genes have confirmed their multifunctional role in stress. Here, we provide an overview of the signal transduction mechanisms and functional roles of CDPKs. This review includes details on the regulation of secondary metabolites, nutrient uptake, regulation of flower development, hormonal regulation, and biotic and abiotic stress responses.

Agricultural drought significantly impacts agricultural production, highlighting the need for accurate monitoring. Accurate agricultural-drought-monitoring models are critical for timely warning and prevention. The random forest (RF) is a popular artificial intelligence method but has not been extensively studied for agricultural drought monitoring. Here, multi-source remote sensing data, including surface temperature, vegetation index, and soil moisture data, were used as independent variables; the 3-month standardized precipitation evapotranspiration index (SPEI_3) was used as the dependent variable. Soil texture and terrain data were used as auxiliary variables. The bias-corrected RF model was used to construct a random forest synthesized drought index (RFSDI). The drought-degree determination coefficients (R2) of the training and test sets reached 0.86 and 0.89, respectively. The RFSDI and SPEI_3 fit closely, with a correlation coefficient (R) above 0.92. The RFSDI accurately reflected typical drought years and effectively monitored agricultural drought in Northeast China (NEC). In the past 18 years, agricultural drought in NEC has generally decelerated. The degree and scope of drought impacts from 2003 to 2010 were greater than those from 2010 to 2020. Agricultural drought occurrence in NEC was associated with dominant climatic variables such as precipitation (PRE), surface temperature (Ts), relative humidity (RHU), and sunshine duration (SSD), alongside elevation and soil texture differences. The agricultural drought occurrence percentage at 50–500 m elevations reached 94.91%, and the percentage of occurrence in loam and sandy soils reached 90.31%. Water and temperature changes were significantly correlated with the occurrence of agricultural drought. Additionally, NEC showed an alternating cycle of drought and waterlogging of about 10 years. These results have significant application potential for agricultural drought monitoring and drought prevention in NEC and demonstrate a new approach to comprehensively evaluating agricultural drought.

The perovskite LaCoO3 and La0.8Sr0.2CoO3 thin films were synthesized successfully by a polymer-assisted deposition method. The structural characterization and thermal decomposition measurements indicate that appropriately increasing the annealing temperature is helpful in improving the film crystallinity. Compared with LaCoO3 films, the Curie temperature is enhanced to a higher temperature in La0.8Sr0.2CoO3 films, which is attributed to the changes in both the valence state and spin state induced by the chemical doping. In addition, a broad transition temperature region is observed in La0.8Sr0.2CoO3 films, revealing the existence of inhomogeneous ground states in this system.

Abstract Recent technical advances have led to the discovery of novel functions of extrachromosomal DNA (ecDNA) in multiple cancer types. Studies have revealed that cancer-associated ecDNA shows a unique circular shape and contains oncogenes that are more frequently amplified than that in linear chromatin DNA. Importantly, the ecDNA-mediated amplification of oncogenes was frequently found in most cancers but rare in normal tissues. Multiple reports have shown that ecDNA has a profound impact on oncogene activation, genomic instability, drug sensitivity, tumor heterogeneity and tumor immunology, therefore may offer the potential for cancer diagnosis and therapeutics. Nevertheless, the underlying mechanisms and future applications of ecDNA remain to be determined. In this review, we summarize the basic concepts, biological functions and molecular mechanisms of ecDNA. We also provide novel insights into the fundamental role of ecDNA in cancer.

Calcium-dependent protein kinases (CDPKs) are a class of serine/threonine protein kinases encoded by several gene families that play key roles in stress response and plant growth and development. In this study, the BLAST method was used to search for protein sequences of the potato Calcium-dependent protein kinase gene family. The chromosome location, phylogeny, gene structures, gene duplication, cis-acting elements, protein-protein interaction, and expression profiles were analyzed. Twenty-five CDPK genes in the potato genome were identified based on RNA-seq data and were clustered into four groups (I-IV) based on their structural features and phylogenetic analysis. The result showed the composition of the promoter region of the StCDPKs gene, including light-responsive elements such as Box4, hormone-responsive elements such as ABRE, and stress-responsive elements such as MBS. Four pairs of segmental duplications were found in StCDPKs genes and the Ka/Ks ratios were below 1, indicating a purifying selection of the genes. The protein-protein interaction network revealed defense-related proteins such as; respiratory burst oxidase homologs (RBOHs) interacting with potato CDPKs. Transcript abundance was measured via RT-PCR between the two cultivars and their relative expression of CDPK genes was analyzed after 15, 20, and 25 days of drought. There were varied expression patterns of StCDPK3/13/21 and 23, between the two potato cultivars under mannitol induced-drought conditions. Correlation analysis showed that StCDPK21/22 and StCDPK3 may be the major differentially expressed genes involved in the regulation of malondialdehyde (MDA) and proline content in response to drought stress, opening a new research direction for genetic improvement of drought resistance in potato.

Induced pluripotent stem cells (iPSCs) have become the leading research object in the clinical application of restorative medicine. They are easily generated from diverse cell sources and functionally indistinguishable from embryonic stem cells without the accompanying ethical issues. To date, the use of iPSC-derived neural stem cells and their progeny in the treatment of neurodegenerative and injurious diseases has achieved good results, with great potential in cell drug development. However, because of some unique biological properties and differences from traditional drug production processes, cell drug research and development has many problems that can hinder clinical applications. Given this situation, the Chinese Association of Neurorestoratology (Preparatory) and China Committee of the International Association of Neurorestoratology have organized relevant professional experts to formulate the standard presented here. Overall, the aim was to promote the clinical application of neural stem cells (NSCs) and their further derived neural cells from iPSC sources and promote cell drugs’ production and development. This standard refers to the latest research results, quality evaluation criteria for traditional medicines, and the regulatory framework for cellular treatments. The standard considers general biological properties of cells, including cell morphology, cell cycle, karyotype, and cell viability. The specific biological properties of NSCs, such as cell surface markers and differentiation ability, general drug standards, such as aseptic testing, endotoxins, human virus detection, and cell-related drug standards, such as telomerase activity and tumorigenicity, are also considered. This standard will serve as a reference for physicians and scientists who focus on clinical nervous cell applications and studies related to iPSCs.

A 3-D frequency-selective rasorbers (FSR) with wide absorption bands at both sides of the transmission window based on stepped impedance resonator (SIR) is presented and investigated in this article. The proposed FSR features thin thickness, wide absorption bands and lumped-element-free characteristics. The transmission channel is constructed from a parallel waveguide based on SIR to provide the transmission path and reduce the thickness of the whole structure. The absorption channel is filled with magnetic absorber to provide a wide absorption band, while meander-line in shunt connection with the absorber is used to avoid lumped components and to obtain a low insertion loss at the passband. The detailed design concept and analysis are illustrated and the fundamental operating principle of the FSR is demonstrated with the help of an equivalent circuit model (ECM). A design example is provided and it exhibits a passband at 7.1 GHz with a transmission bandwidth of 22.6% for less than 3 dB insertion loss and fractional bandwidth of 128.0% with reflectivity less than -10 dB. Moreover, one dual-polarized FSR is also designed and analyzed to generalize the design strategy. Both single- and dual-polarized prototypes are designed, fabricated, and measured to verify the design concept. Good agreement can be observed between the simulated and measured results.

This article is oriented to the research of the vehicle-mounted intelligent traditional Chinese medicine (TCM) syndrome differentiation system to provide a quick and accurate diagnosis suggestion for smart and mobile medical vehicles. Nowadays, TCM modernization has attached more and more attention due to its remarkable clinical effect. The typical TCM diagnosis process is to induces the syndrome types of a patient from the four-diagnosis symptoms based on syndrome differentiation theory, that is, given a set of symptoms to treat, an overall syndrome representation is learned by fusing all the symptoms effectively to mimic how a doctor induce the syndromes. Therefore, we believe that an overall description of symptoms of a patient is very important for the follow-up treatment and should be handled carefully and properly. However, due to the complexity and diversity of syndromes, most recommended prescription of a patient lacks the explicit ground-truth of syndrome. Therefore, in this article, a new TCM syndrome differentiation method based on multi-label classification method and deep learning method was proposed to learn the implicit symptoms induction process in the real diagnosis. A Deep Belief Network (DBN) was used to reconstruct the TCM diagnosis model based on the Rrestricted Boltzman Machine (RBM) mechanism. Towards symptoms-syndrome groups learning, a symptom vector representing the symptom collection of a patient is constructed as the input of DBN, which was used to train the symptom data and labeled samples to build an unsupervised model at first. And then the parameters of DBN was adjusted gradually based on back propagation method. Secondly, binary classification algorithm was used to convert the multi-label classification problem into several corresponding labels. Each binary classifier model corresponds to a binary classifier to complete the classification from symptoms to corresponding syndrome types. Finally, Experiments were conducted on a self-built TCM clinical records database, demonstrating obvious improvements on the classification accuracy and convergence rate. Further studies should focus on the promotion of effectiveness of the proposed model to be more in line with the actual needs of onboard medical diagnosis and treatment.

Due to optical noise, electrical noise, and compression error, data hyperspectral remote sensing equipment is inevitably contaminated by various noises, which seriously affect the applications of hyperspectral data. Therefore, it is of great significance to enhance hyperspectral imaging data quality. To guarantee the spectral accuracy during data processing, band-wise algorithms are not suitable for hyperspectral data. This paper proposes a quality enhancement algorithm based on texture search and histogram redistribution combined with denoising and contrast enhancement. Firstly, a texture-based search algorithm is proposed to improve the accuracy of denoising by improving the sparsity of 4D block matching clustering. Then, histogram redistribution and Poisson fusion are used to enhance spatial contrast while preserving spectral information. Synthesized noising data from public hyperspectral datasets are used to quantitatively evaluate the proposed algorithm, and multiple criteria are used to analyze the experimental results. At the same time, classification tasks were used to verify the quality of the enhanced data. The results show that the proposed algorithm is satisfactory for hyperspectral data quality improvement.

Sucrose non-ferment 1-related protein kinase 2 (SnRK2) is a highly conserved protein kinase in plants that plays an important role in regulating plant response to drought stress. Although it has been reported in some plants, the evolutionary relationship of potato SnRK2s and their function in drought resistance have not been systematically analyzed. In this study, molecular characteristic analysis showed that 8 StSnRK2s were distributed on six chromosomes, coding proteins were divided into three subgroups, and StSnRK2s clustered in the same subgroup had similar conserved motifs and domains. In addition, StSnRK2 has a wide range of replication events in some species, making it closer to dicots in the process of evolution. In addition, the average nonsynonymous substitution rate/synonymous substitution rate (Ka/Ks) value of SnRK2s in monocots was higher than that of dicots. The codon usage index showed that SnRK2s prefer to use cytosine 3 (C3s), guanine 3 (G3s) and GC content (GC3s) in monocots, whereas thymine 3 (T3s) and adenine 3 (A3s) are preferred in dicots. Furthermore, stress response analysis showed that the expression of StSnRK2s under different degrees of drought stress significantly correlated with one or more stress-related physiological indices, such as proline and malondialdehyde (MDA) content, superoxide dismutase (SOD) and catalase (CAT) activity, ion leakage (IL) etc. The drought resistance of StSnRK2 transgenic plants was determined to occur in the order of StSnRK2.1/2.8 > StSnRK2.2/2.5 > StSnRK2.4/2.6 > StSnRK2.3 > StSnRK2.7, was attributed to not only lower IL but also higher proline, soluble sugar contents and stress-related genes in transgenic plants compared to wild type (WT). In conclusion, this study provides useful insights into the evolution and function of StSnRK2s and lays a foundation for further study on the molecular mechanism of StSnRK2s regulating potato drought resistance.

ABSTRACT Human neutrophil peptide-1 (HNP-1) is a promising antibiotic candidate, but its clinical applications have been hampered by challenges during mass production and an inadequate understanding of its bactericidal mechanisms. In this study, we demonstrated that Escherichia coli expressing full-length preproHNP-1 secretes a soluble form of HNP-1, which can be recovered from the total cell lysate after isopropyl thio-β-d-galactoside (IPTG) induction and ultrafiltration. Label-free quantitative proteomics and co-immunoprecipitation experiments revealed that HNP-1 induces cell apoptosis in bacteria by causing DNA and membrane damage. Notably, we found that HNP-1 disrupts the DNA damage response pathway by interfering with the binding of RecA to single-stranded DNA (ssDNA). Further experiments demonstrated that HNP-1 encapsulated in liposomes inhibits the growth of methicillin-resistant Staphylococcus aureus (MRSA) and meropenem-resistant Pseudomonas aeruginosa (MRPA). These results indicated that recombinant protein expression may be a simple and cost-effective solution to produce HNP-1 and that RecA inhibition via HNP-1 may serve as an alternative strategy to counteract antibiotic resistance. IMPORTANCE Human neutrophil peptide-1 (HNP-1) is a promising antibiotic candidate, but its clinical application has been hampered by the difficulty of mass production and an inadequate understanding of its bactericidal mechanisms. In this study, we demonstrated that recombinant protein expression combined with ultrafiltration may be a simple and cost-effective solution to HNP-1 production. We further found that HNP-1 induces bacterial apoptosis and prevents its SOS repair pathway from binding to the RecA protein, which may be a new antibacterial mechanism. In addition, we showed that HNP-1 encapsulated in liposomes inhibits the growth of methicillin-resistant Staphylococcus aureus (MRSA) and meropenem-resistant Pseudomonas aeruginosa (MRPA). These results provide new insights into the production and antibacterial mechanism of HNP-1, both of which may promote its clinical application.

Background. Nonstructural maintenance of non-SMC condensin I complex subunit G (NCAPG) exerts critical effects on cancer progression. However, its biological roles in tumorigenesis and metastasis remain unclear. Thus, we aimed to assess the prognostic utility of NCAPG in stomach adenocarcinoma (STAD) and its potential as a tumor biomarker. Methods. Pan-cancer expression profile dataset from public databases and corresponding clinical information were extracted. Single-sample gene set enrichment analysis (ssGSEA) was performed for the evaluation of immune correlations pan-cancer. Subsequently, we focused on STAD and evaluated the methylation profiles, copy number variants (CNVs), and single nucleotide variants (SNVs). Immune features were analyzed between high and low NCAPG expression groups. Differential analysis was performed between high and low expression groups to identify differentially expressed genes (DEGs). Prognostic DEGs were screened by univariate analysis, and an NCAPG-based risk model was constructed based on the prognostic DEGs and LASSO analysis. Results. NCAPG expression in STAD was significantly and positively correlated with four immune checkpoints, namely, CTLA4, PDCD1, LAG3, and CD276, but was negatively correlated with the infiltration of most immune cells. High and low NCAPG expression groups had differential overall survival, tumor mutation burden, and differential enrichment of therapeutic-related pathways. An immune risk scoring model related to NCAPG expression and immune score was constructed which showed a favorable performance in predicting STAD prognosis as well as predicting the response to immunotherapy. In addition, we found a higher mRNA stemness index (mRNAsi) in the high-risk group and a positive correlation between NCAPG expression and mRNAsi. Conclusion. NCAPG was suggested to be involved in the regulation of tumor microenvironment in STAD. High NCAPG expression was related to high tumor stemness and good prognosis. The immune risk model had a potential to predict STAD prognosis and help directing therapeutic treatment.

Chimeric antigen receptor T (CAR-T) cells show good efficacy in the treatment of relapsed and refractory B-cell tumors, such as acute B-cell leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). The main toxicities of CAR-T include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenia, and severe infection. It is still very difficult for CAR-T to kill tumor cells to the maximum extent and avoid damaging normal organs. Here, we report a case of DLBCL with persistent grade 4 thrombocytopenia and severe platelet transfusion dependence treated with CD19 CAR-T cells. We used sirolimus to inhibit the sustained activation of CAR-T cells and restore normal bone marrow hematopoiesis and peripheral blood cells. Moreover, sirolimus treatment did not affect the short-term efficacy of CAR-T cells, and DLBCL was in complete remission at the end of follow-up. In conclusion, sirolimus can represent a new strategy for the management of CAR-T cell therapy-related toxicity, including but not limited to hematotoxicity. However, further controlled clinical studies are required to confirm these findings.

Glioma is the most common malignancy of the central nervous system. Although advances in surgical resection, adjuvant radiotherapy, and chemotherapy have been achieved in the last decades, the prognosis of gliomas is still dismal. COL5A1 is one of the collagen members with minor content but prominent functions. The present study examined the biological functions, prognostic value, and gene-associated tumor-infiltrating immune cells of COL5A1 through experiments and bioinformatics analysis. We found that the overexpression of COL5A1 was positively correlated with the increasing tumor malignancies and indicated poor prognosis in gliomas. Moreover, downregulation of COL5A1 could inhibit proliferation and migration of glioma cells and enhance their temozolomide sensitivities in vitro. Further bioinformatic analysis revealed that COL5A1 and its co-expressed genes participated in a number of pathways and biological processes involved in glioma progression. Finally, we evaluated the tumor-infiltrating immune cells of gliomas depending on COL5A1 and found that the percentages of the dendritic cells, which were known as the central mediator of tumor microenvironment in gliomas, were positively associated with the expression levels of COL5A1. Taken together, COL5A1 is an important biomarker and potential therapeutic target of gliomas.

Whether DNA methylation modification affects the gene transcription and expression of potatoes under drought stress is still unknown. In this study, we used comparative transcriptomics to explore the expression pattern of related genes of the drought-tolerant variety Qingshu 9 (Q) and the drought-sensitive variety Atlantic (A) under drought stress and DNA methylation inhibitor treatment. The results showed that there was a significant difference in the number of DEGs between the two varieties’ responses to mannitol and 5-azad C, especially when they were co-treated with two reagents, and the gene expression of Q was more sensitive to mannitol after two hours. Furthermore, we found that these differentially expressed genes (DEGs) were significantly enriched in DNA replication, transcription, translation, carbohydrate metabolism, photosynthesis, signal transduction, and glutathione metabolism. These results indicate that the difference in the background of methylation leads to the difference in drought resistance of the two varieties. The complexity of the DNA methylation of variety Q might be higher than that of variety A, and the method of methylation regulation is more refined. This study systematically expands the understanding of the molecular mechanism wherein DNA methylation regulates the response to drought stress.

Crop growth and development are frequently affected by biotic and abiotic stresses. The adaptation of crops to stress is mostly achieved by regulating specific genes. The root system is the primary organ for nutrient and water uptake, and has an important role in drought stress response. The improvement of stress tolerance to increase crop yield potential and yield stability is a traditional goal of breeders in cultivar development using integrated breeding methods. An improved understanding of genes that control root development will enable the formulation of strategies to incorporate stress-tolerant genes into breeding for complex agronomic traits and provide opportunities for developing stress-tolerant germplasm. We screened the genes associated with root growth and development from diverse plants including Arabidopsis, rice, maize, pepper and tomato. This paper provides a theoretical basis for the application of root-related genes in molecular breeding to achieve crop drought tolerance by the improvement of root architecture.

The selection and breeding of deep rooting and drought-tolerant varieties has become a promising approach for improving the yield and adaptability of potato (Solanum tuberosum L.) in arid and semiarid areas. Therefore, the discovery of root-development-related genes and drought tolerance signaling pathways in potato is important. In this study, we used deep-rooting (C119) and shallow-rooting (C16) potato genotypes, with different levels of drought tolerance, to achieve this objective. Both genotypes were treated with 150 mM mannitol for 0 h (T0), 2 h (T2), 6 h (T6), 12 h (T12), and 24 h (T24), and their root tissues were subjected to comparative transcriptome analysis. A total of 531, 1571, 1247, and 3540 differentially expressed genes (DEGs) in C16 and 1531, 1108, 674, and 4850 DEGs in C119 were identified in T2 vs. T0, T6 vs. T2, T12 vs. T6, and T24 vs. T12 comparisons, respectively. Gene expression analysis indicated that a delay in the onset of drought-induced transcriptional changes in C16 compared with C119. Functional enrichment analysis revealed genotype-specific biological processes involved in drought stress tolerance. The metabolic pathways of plant hormone transduction and MAPK signaling were heavily involved in the resistance of C16 and C119 to drought, while abscisic acid (ABA), ethylene, and salicylic acid signal transduction pathways likely played more important roles in C119 stress responses. Furthermore, genes involved in root cell elongation and division showed differential expression between the two genotypes under drought stress. Overall, this study provides important information for the marker-assisted selection and breeding of drought-tolerant potato genotypes.

In this paper, we consider the robust stabilization control problem of underactuated translational oscillator with a rotating actuator (TORA) system in the presence of unknown matched disturbances by employing continuous control inputs. A nonlinear continuous robust control approach is proposed by integrating the techniques of backstepping and linear extended state observer (LESO). Specifically, based on the backstepping design methodology, a hyperbolic tangent virtual control law is designed for the first subsystem of the cascaded TORA model, via which an integral chain error subsystem is subsequently constructed and the well-known LESO technique is easy to implement. Then, an LEO is designed to estimate the lumped matched disturbances in real-time, and the influence of the disturbances is compensated by augmenting the feedback controller with the disturbance estimation. The convergence and stability of the entire control system are rigorously proved by utilizing Lyapunov theory and LaSalle’s invariance principle. Unlike some existing methods, the proposed controller is capable of generating robust and continuous control inputs, which guarantee that both the rotation and translation of TORA systems are stabilized at the origin simultaneously and smoothly, attenuating the influence of disturbances. Comparative simulation results are presented to demonstrate the effectiveness and superior control performance of the proposed method.