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Abstract Moisture content of rock/coal can change its mechanical properties and absorption capacities, which can directly affect gas diffusivity, change the stress distribution and hence cause significant impacts on the overall gas or coal extraction process. Observation of the water penetration process and water distribution in the coal matrix will be beneficial for the understanding of the fluid-solid coupling mechanism in hydraulic fracturing, aquifer cracking and coal seam infusion. However, the observation of water penetration process and the determination of water distribution mode were hard to be non-destructively achieved as coal is a non-uniform, inhomogeneous and un-transparent material. µ-CT imaging, which is based on variation of X-ray attenuation related to the density and atomic composition of the scanned objects, enables a four-dimensional (spatial-temporal) visualise of the heterogeneous and anisotropic coal samples. The primary aim of this paper is extending the application of µ-CT imaging to explore the moisture penetration and distribution within coal samples during water infusion process, which has been reported by very little literature. The working principle and procedures of CT imaging was firstly introduced. Then, the determination equation of moisture distribution based on density profile was established. The CT determined moisture content has been compared with weighting method for verification. The paper has demonstrated that µ-CT can be used for non-destructively imaging the moisture distribution within coal samples.

Fatigue is an important cause of traffic crashes, and effective fatigue detection models can reduce these crashes. Research has found large differences in fatigued driving performance from driver to driver, as well as a significant cumulative effect of fatigue on a given driver over time. Both sources of variation can decrease the accuracy of detection systems, but previous studies have not done enough to evaluate these differences. The purpose of this study is therefore to develop a fatigue detection model that considers individual differences and the time cumulative effect of fatigue. Data on the lateral position of the car in its lane, steering wheel movement, speed, and eye movement were collected from 22 drivers using a driving simulator with an eye-tracking system. Drivers’ subjective fatigue scores were collected using the Karolinska Sleepiness Scale. State space models (SSMs) were built to detect fatigue in each driver, considering his or her individual features. As a time series model, the SSM can also address the time cumulative effect of fatigue, and it does not require a large dataset to achieve high levels of accuracy. The differences in SSM results confirm that diversity does exist among drivers’ fatigued driving performance, so the ability of the SSM to take into account driver-specific information from each individual driver suggests that it is more suitable for fatigue detection than models that use aggregated driver data. Results show that the fatigue detection accuracy of the SSM (77.73%) is higher than that of artificial neural network models (61.37%). The advantages of accuracy, high interpretability, and flexibility make the SSM a comprehensive and valuable individualized fatigue detection model for commercial use.

Background and aims: Bone marrow failure (BMF) is chronic benzene-induced hematotoxicity, which is associated with differential gene expression abnormality. Benzene-induced BMF is characterized by irreversible bone marrow depression. Despite extensive studies have been conducted, there is a lack of reliable, useful and simple diagnostic method for BMF. Previous studies have shown that the aberrant gene expression changes and reactive oxygen species production in bone marrow cells related to the development of BMF. Early detection of differentially expressed genes (DEGs) as potential biomarkers is important for diagnosis and treatment. However, the validation of effective biomarker through DEGs analysis in benzene-induced BMF still deserve to be clarified. This study aimed to identify target genes as potential biomarkers with benzene-induced BMF based on DEGs analysis. Methods: First, we developed a benzene-induced BMF mouse model and obtained the DEGs in bone marrow cells of benzene-exposed CD1 mice. Next, after obtaining the DEGs via RNA-Sequencing (RNA-seq) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also used, key genes associated with benzene-induced BMF were identified. Additionally, the key markers for benzene poisoning was evaluated using qRT-PCR technique. Results: We identified DEGs for further KEGG functional analysis. Ten statistically significantly (up or down) regulated genes, namely Mapk11, Foxo1, Lefty1, Ren1, Bank1, Fgf3, Cdc42ep2, Rasgrf1, P2rx7, and Shank3 were found mainly associated with mitogen-activated protein kinases (MAPK) oxidative stress pathway. Further analysis using qRT-PCR identified that eight statistically significant DEGs associated with signaling pathways such as MAPK. We found that the level of mRNA expression of Mapk11, Foxo1, Bank1, Lefty1, Ren1, P2rx7, and Fgf3 genes were increased and Cdc42ep2 gene was decreased in BMF mice compared to control mice. Additionally, we validated the eight candidate genes for potential biomarkers in peripheral blood mononuclear cells of benzene poisoning patients by qRT-PCR. Conclusion: Our results indicated that Mapk11 and Fgf3 were predominantly candidate genes linked to novel biomarkers for benzene hematotoxicity in human beings. Our study will provide new candidate genes as useful biomarkers involved in benzene-induced hematotoxicity.

BackgroundThe hospital supply chain has revealed increasing vulnerabilities and disruptions in the wake of the COVID-19 pandemic, threatening the healthcare services and patient safety. The resilience of hospital supply chains has emerged as a paramount concern within the healthcare system. However, there is a lack of systematic research to develop an instrument tailored to the healthcare industry that is both valid and reliable for measuring hospital supply chain resilience. Therefore, this study aims to construct and validate a comprehensive scale for assessing hospital supply chain resilience, based on dynamic capability theory.MethodsThis study followed rigorous scale development steps, starting with a literature review and 15 semi-structured interviews to generate initial items. These items were then refined through expert panel feedback and three rounds of Delphi studies. Using data from 387 hospitals in Province S, mainland China, the scale underwent rigorous testing and validation using structural equation modeling. To ensure the most effective model, five alternative models were examined to determine the most suitable parsimonious model.ResultsThe study produced a 26-item scale that captures five dimensions of resilience in line with dynamic capability theory: anticipation, adaptation, response, recovery, and learning, all showing satisfactory consistency, reliability and validity.ConclusionThe multi-dimensional scale offers hospital managers a valuable tool to identify areas needing attention and improvement, benchmark resilience against their counterparts, and ultimately strengthen their supply chains against unexpected risks.

Abstract Background Silicosis is an important occupational disease caused by inhalation of free silica and is characterized by persistent pulmonary inflammation, subsequent fibrosis and lung dysfunction. Until now, there has been no effective treatment for the disease due to the complexity of pathogenesis. Fermented cordyceps powder (FCP) has a similar effect to natural cordyceps in tonifying the lung and kidney. It has started to be used in the adjuvant treatment of silicosis. This work aimed to verify the protective effects of FCP against silicosis, and to explore the related mechanism. Methods Wistar rats were randomly divided into four groups including the saline-instilled group, the silica-exposed group, the silica + FCP (300 mg/kg) group and the silica + FCP (600 mg/kg) group. Silicosis rat models were constructed by intratracheal instillation of silica (50 mg). Rats in the FCP intervention groups received the corresponding dose of FCP daily by intragastric gavage. Rats were sacrificed on days 7, 28 and 56 after treatment, then samples were collected for further analysis. Results FCP intervention reduced the infiltration of inflammatory cells and the concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) at days 7, 28, 56, and decreased the expression of collagen, α-smooth muscle actin (α-SMA) and fibronectin (FN) at days 28 and 56 in the lung of silicosis rats. FCP also decreased the immune response of Th1 and Th17 at days 7, 28, 56 and inhibited the enhancement of the Th2 response at day 56. Conclusions FCP intervention could alleviate silica-induced pulmonary inflammation and fibrosis, the protective effect may be achieved by reducing Th1 and Th17 immune responses and inhibiting the enhancement of the Th2 response.

Plants are complex systems hierarchically organized and composed of various cell types. To understand the molecular underpinnings of complex plant systems, single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for revealing high resolution of gene expression patterns at the cellular level and investigating the cell-type heterogeneity. Furthermore, scRNA-seq analysis of plant biosystems has great potential for generating new knowledge to inform plant biosystems design and synthetic biology, which aims to modify plants genetically/epigenetically through genome editing, engineering, or re-writing based on rational design for increasing crop yield and quality, promoting the bioeconomy and enhancing environmental sustainability. In particular, data from scRNA-seq studies can be utilized to facilitate the development of high-precision Build–Design–Test–Learn capabilities for maximizing the targeted performance of engineered plant biosystems while minimizing unintended side effects. To date, scRNA-seq has been demonstrated in a limited number of plant species, including model plants (e.g., Arabidopsis thaliana), agricultural crops (e.g., Oryza sativa), and bioenergy crops (e.g., Populus spp.). It is expected that future technical advancements will reduce the cost of scRNA-seq and consequently accelerate the application of this emerging technology in plants. In this review, we summarize current technical advancements in plant scRNA-seq, including sample preparation, sequencing, and data analysis, to provide guidance on how to choose the appropriate scRNA-seq methods for different types of plant samples. We then highlight various applications of scRNA-seq in both plant systems biology and plant synthetic biology research. Finally, we discuss the challenges and opportunities for the application of scRNA-seq in plants.

ABSTRACTPersistent high-risk human papillomavirus (HPV) infection is the pivotal cause of cervical carcinogenesis. HPV types distribution varies greatly by region, and its long-term changes of prevalence remain to be fully characterized in China. Here, the largest population of 198,111 consecutive women who underwent routine cervical screening were investigated from 2015 to 2021 in Guangzhou, south China. The results showed that the overall HPV prevalence was 21.66% (42,911/198,111), and the annual prevalence increased significantly from 2015 to 2021 (p

Abstract Background The internal limiting membrane (ILM) insertion technique was widely used to treat large macular hole (MH) for the high closure rate. However, the prognosis of closed MH after ILM insertion compared to ILM peeling remains controversial. This study aimed to compare foveal microstructure and microperimeter in large idiopathic MH surgically closed by ILM peeling and ILM insertion. Methods This retrospective, non-randomized, comparative study included patients with idiopathic MH (minimum diameter ≥ 650 μm) who underwent primary pars plana vitrectomy (PPV) with ILM peeling or ILM insertion. The initial closure rate was recorded. Patients with initially closed MHs were divided into two groups according to the surgery methods. The best-corrected visual acuity (BCVA), optical coherence tomography (OCT) and microperimeter-3 (MP-3) outcomes of two groups were compared at baseline, 1 and 4 months postoperatively. Results For idiopathic MH (minimum diameter ≥ 650 μm), ILM insertion had a significantly higher initial closure rate than ILM peeling (71.19% vs. 97.62%, P = 0.001). Among 39 patients with initially closed MHs who were on regular follow-up, twenty-one were assigned to the ILM peeling group and 18 to the ILM insertion group. Postoperative BCVA improved significantly in both groups. The final BCVA (logMAR) (0.40 vs. 0.88, P

To study the influence of inclusions on the fracture evolution and mechanical properties of mortar structures, a series of uniaxial compression tests for mortar samples containing cylinder inclusions of varying mechanical properties were conducted. The digital image correlation (DIC) technique was employed for the analysis of deformation characteristics. In addition, failure modes for each sample were determined using self-documenting code. The result shows that inclusions filled in holes significantly influence the mechanical properties and failure characteristics of mortar structures as they can change the stress distribution and cracking process. Cracks are typically initiated at the boundaries of the inclusions but will only extend into the inclusion if it is less robust than the surrounding matrix. Sample strength increases significantly with an increase in sample strength when the inclusion’s strength does not surpass that of the surrounding material. Once the inclusion’s strength exceeds that of the surrounding matrix, the strength of the specimen remains relatively unchanged.

Abstract The ability to stack multiple genes in plants is of great importance in the development of crops with desirable traits but can be challenging due to limited selectable marker options. Here we establish split selectable marker systems using protein splicing elements called “inteins” for Agrobacterium-mediated co-transformation in plants. First, we show that such a split selectable marker system can be used effectively in plants to reconstitute a visible marker, RUBY, from two non-functional fragments through tobacco leaf infiltration. Next, to determine the general applicability of our split selectable marker systems, we demonstrate the utility of these systems in the model plants Arabidopsis and poplar by successfully stacking two reporters eYGFPuv and RUBY, using split Kanamycin or Hygromycin resistance markers. In conclusion, this method enables robust plant co-transformation, providing a valuable tool for the simultaneous insertion of multiple genes into both herbaceous and woody plants efficiently.

Well-developed pores and cracks in coal reservoirs are the main venues for gas storage and migration. To investigate the multi-scale pore fractal characteristics, six coal samples of different rankings were studied using high-pressure mercury injection (HPMI), low-pressure nitrogen adsorption (LPGA-N2), and scanning electron microscopy (SEM) test methods. Based on the Frankel, Halsey and Hill (FHH) fractal theory, the Menger sponge model, Pores and Cracks Analysis System (PCAS), pore volume complexity (Dv), coal surface irregularity (Ds) and pore distribution heterogeneity (Dp) were studied and evaluated, respectively. The effect of three fractal dimensions on the gas adsorption ability was also analyzed with high-pressure isothermal gas adsorption experiments. Results show that pore structures within these coal samples have obvious fractal characteristics. A noticeable segmentation effect appears in the Dv1 and Dv2 fitting process, with the boundary size ranging from 36.00 to 182.95 nm, which helps differentiate diffusion pores and seepage fractures. The D values show an asymmetric U-shaped trend as the coal metamorphism increases, demonstrating that coalification greatly affects the pore fractal dimensions. The three fractal dimensions can characterize the difference in coal microstructure and reflect their influence on gas adsorption ability. Langmuir volume (VL) has an evident and positive correlation with Ds values, whereas Langmuir pressure (PL) is mainly affected by the combined action of Dv and Dp. This study will provide valuable knowledge for the appraisal of coal seam gas reservoirs of differently ranked coals.

Electro-hydraulic servo system (EHSS) plays an important role in many industrial and military applications. However, its high-performance tracking control is still a challenging mission due to its nonlinear system dynamics and model uncertainties. In this paper, a novel adaptive robust integral method of the sign of the error (ARISE) with extended state observer (ESO) is proposed. Firstly, the nonlinear mathematical model of typical EHSS with modeling uncurtains and uncertain nonlinear is established. Then, ESO is used to estimate the state and lumped disturbance, of which the unknown parameter estimations can be updated by the novel adaptive law. Results shows that the novel controller achieves better tracking performance in maximum tracking error, average tracking error and standard deviation of the tracking error.

Abstract The Salicaceae family is of growing interest in the study of dioecy in plants because the sex determination region (SDR) has been shown to be highly dynamic, with differing locations and heterogametic systems between species. Without the ability to transform and regenerate Salix in tissue culture, previous studies investigating the mechanisms regulating sex in the genus Salix have been limited to genome resequencing and differential gene expression, which are mostly descriptive in nature, and functional validation of candidate sex determination genes has not yet been conducted. Here, we used Arabidopsis to functionally characterize a suite of previously identified candidate genes involved in sex determination and sex dimorphism in the bioenergy shrub willow Salix purpurea. Six candidate master regulator genes for sex determination were heterologously expressed in Arabidopsis, followed by floral proteome analysis. In addition, 11 transcription factors with predicted roles in mediating sex dimorphism downstream of the SDR were tested using DAP‐Seq in both male and female S. purpurea DNA. The results of this study provide further evidence to support models for the roles of ARR17 and GATA15 as master regulator genes of sex determination in S. purpurea, contributing to a regulatory system that is notably different from that of its sister genus Populus. Evidence was also obtained for the roles of two transcription factors, an AP2/ERF family gene and a homeodomain‐like transcription factor, in downstream regulation of sex dimorphism.

Exposure to toluene diisocyanate (TDI) can cause pulmonary diseases such as asthma. Inhibition of high mobility group box 1 protein (HMGB1) has been found to be protective against the toxic effects of TDI on human bronchial epithelial (HBE) cells. Here, we evaluated the in vivo positive roles of HMGB1 in the TDI-caused asthma mice and explored its underlying mechanisms in HBE cells. We found that suppression of HMGB1 obviously alleviated airway inflammation, airway hyperresponsiveness, and airway remodeling in the lung tissue of the asthma mice. The in vitro results showed that inhibition of HMGB1 ameliorated TDI-induced reactive oxygen species (ROS) release, inflammatory response, and activation of autophagy in HBE cells. At the molecular level, inhibition of HMGB1 decreased the expressions of HMGB1, Toll-like receptor 4, Vimentin and matrix metalloproteinase-9 proteins, activated NF-κB and NOD-like receptor protein 3 (NLRP3) inflammasome, and increased E-cadherin expression. Importantly, activation of autophagy could lead to the overactivation of NLRP3 inflammasome in TDI-induced asthma. These results suggest that inhibition of HMGB1 can alleviate TDI-induced asthma through ROS/AMPK/autophagy pathways, which may provide valuable evidence for the pathogenesis and therapeutic targets of TDI-induced asthma.

Abstract Under the effects of complex geological and stress environments, burst hazards continue to be a major challenge for underground space utilization and deep resources exploration as its occurrence can lead to personnel causalities, equipment damage and structural collapse. Considering the stress path experienced by in-situ coal body, cyclic loading appears in quite various forms for instance shearer cutting, overlying strata breakage, hydro-fracturing and blasting, during tunnel, mining and underground space utilizing process. The stability of the underground coal body subject to periodic loading/unloading stress is extremely important for maintain the function of designed engineering structure for waste storage, safe mining, roadway development, gas recovery, carbon sequestration and so on. The mechanical properties of hard rock subject to cyclic fatigue loads has been intensively investigated by many researchers as the rock burst induced by supercritical loads has long been a safety risk and engineering problems for civil and tunneling engineering under deep overburden. More recently, the mechanical properties of coal samples under cyclic fatigue loads is investigated from the aspect of hysteresis, energy dissipation and irreversible damage as the burst hazards of brittle coal is rising in many countries. However, the crack propagation and fracture pattern of brittle coal need more research to understand the micro mechanism of burst incubation subject to cyclic fatigue loads as brittle coal can store more elastic strain energy and rapidly release the energy when its ultimate strength once reached. This research studied the internal crack status corresponding to different cyclic fatigue loading stage of brittle coal samples. The AE monitoring was applied during the uniaxial and cyclic loading process of brittle coal samples to record the crack intensity of samples at different loading stages. The damage evolution curve corresponding to loading status was then determined. The fracture pattern of coal samples determined by micro-CT scan was observed and discussed. It has been found by this paper that brittle coal of uniaxial compression tests demonstrated sudden failure caused by major splitting fracture while that of cyclic fatigue tests experienced progressive failure with mixture fracture network.

Abstract Background Enterovirus (EV) infections are being increasingly seen in younger infants, often being more severe than in older children. The risk factors of EV infection in infants have been inadequately investigated till date. Methods We conducted a retrospective study on hospitalized children with laboratory-confirmed EV infection (50 infants aged 0–3 months and 65 older than 3 months) at a tertiary care center in China. Prevalence, clinical characteristics, and genetic features of the virus were analyzed, and independent predictors for severe infection were assessed. Results Clinical findings showed that severe infection was more common in infants aged 0–3 months than in older children (78.0% vs. 35.4%, p

In the face of an increasingly intricate network structure and a multitude of security threats, cyber deception defenders often employ deception assets to safeguard critical real assets. However, when it comes to the intranet lateral movement attackers in the cyber kill chain, the deployment of deception assets confronts the challenges of lack of dynamics, inability to make real-time decisions, and not considering the dynamic change of an attacker’s strategy. To address these issues, this study introduces a novel maze pathfinding model tailored to the lateral movement context, in which we try to find out the attacker’s location to deploy deception assets accurately for interception. The attack–defense process is modeled as a multi-agent stochastic game, by comparing it with random action policy and Minimax-Q algorithm, we choose Nash Q-learning to solve the deception asset’s deployment strategy to achieve the optimal solution effect. Extensive simulation tests reveal that our proposed model exhibits good convergence properties. Moreover, the average defense success rate surpasses 70%, attesting to the model’s efficacy.

ABSTRACTThe epidemiological and clinical aspects of Human Papillomavirus (HPV) infection in women have been extensively studied. However, there is a lack of information regarding HPV characteristics in males. In this study, we conducted a retrospective and observational study of 3737 consecutive male individuals attending outpatient clinics of Guangdong Women and Children Hospital from 2012 to 2023 in Guangzhou, South China, to determine the age- and genotype-specific prevalence of HPV in men. The results showed the overall prevalence of HPV among men was 42.15% (1575/3737), with variations ranging from 29.55% to 81.31% across distinct diagnostic populations. Low-risk HPV6 (15.47%), HPV11 (8.94%), and high-risk HPV52 (5.51%) were the most common types. The annual HPV prevalence decreased significantly (Z = −3.882, p

ABSTRACTBackground Enteroviruses (EV) are common and can cause severe diseases, particularly in young children. However, the information of EV infection in infants in China is limited due to the vast population size and extensive geographical area of the country. Here, we conducted a retrospective multicenter analysis of available EV data to assess the current epidemiological situation in the infant population in southern China.Methods The study enrolled infants with suspected EV infection from 34 hospitals across 12 cities in southern China between 2019 to 2022, and the confirmation of EV was done using RT-PCR and VP1 gene sequencing.Results Out of 1221 infants enrolled, 330 (27.03%) were confirmed as EV-infected. Of these, 260 (78.79%) were newborns aged 0–28 days. The EV belonged to three species: EV-B (80.61%), EV-A (11.82%), and human rhinovirus (7.58%). Newborns were more susceptible to EV-B than older infants (p

Abstract Background Contact patterns play a key role in the spread of respiratory infectious diseases in human populations. During the COVID-19 pandemic, the regular contact patterns of the population have been disrupted due to social distancing both imposed by the authorities and individual choices. Many studies have focused on age-mixing patterns before the COVID-19 pandemic, but they provide very little information about the mixing patterns in the COVID-19 era. In this study, we aim at quantifying human heterogeneous mixing patterns immediately after lockdowns implemented to contain COVID-19 spread in China were lifted. We also provide an illustrative example of how the collected mixing patterns can be used in a simulation study of SARS-CoV-2 transmission. Methods and results In this work, a contact survey was conducted in Chinese provinces outside Hubei in March 2020, right after lockdowns were lifted. We then leveraged the estimated mixing patterns to calibrate a mathematical model of SARS-CoV-2 transmission. Study participants reported 2.3 contacts per day (IQR: 1.0–3.0) and the mean per-contact duration was 7.0 h (IQR: 1.0–10.0). No significant differences in average contact number and contact duration were observed between provinces, the number of recorded contacts did not show a clear trend by age, and most of the recorded contacts occurred with family members (about 78%). The simulation study highlights the importance of considering age-specific contact patterns to estimate the COVID-19 burden. Conclusions Our findings suggest that, despite lockdowns were no longer in place at the time of the survey, people were still heavily limiting their contacts as compared to the pre-pandemic situation.

Abstract The chromatin-based rule governing the selection and activation of replication origins remains to be elucidated. It is believed that DNA replication initiates from open chromatin domains; thus, replication origins reside in open and active chromatin. However, we report here that lysine-specific demethylase 1 (LSD1), which biochemically catalyzes H3K4me1/2 demethylation favoring chromatin condensation, interacts with the DNA replication machinery in human cells. We find that LSD1 level peaks in early S phase, when it is required for DNA replication by facilitating origin firing in euchromatic regions. Indeed, euchromatic zones enriched in H3K4me2 are the preferred sites for the pre-replicative complex (pre-RC) binding. Remarkably, LSD1 deficiency leads to a genome-wide switch of replication from early to late. We show that LSD1-engaged DNA replication is mechanistically linked to the loading of TopBP1-Interacting Checkpoint and Replication Regulator (TICRR) onto the pre-RC and subsequent recruitment of CDC45 during origin firing. Together, these results reveal an unexpected role for LSD1 in euchromatic origin firing and replication timing, highlighting the importance of epigenetic regulation in the activation of replication origins. As selective inhibitors of LSD1 are being exploited as potential cancer therapeutics, our study supports the importance of leveraging an appropriate level of LSD1 to curb the side effects of anti-LSD1 therapy.

High-precision bioengineering and synthetic biology require fine-tuning gene expression at both transcriptional and posttranscriptional levels. Gene transcription is tightly regulated by promoters and terminators. Promoters determine the timing, tissues and cells, and levels of the expression of genes. Terminators mediate transcription termination of genes and affect mRNA levels posttranscriptionally, e.g., the 3′-end processing, stability, translation efficiency, and nuclear to cytoplasmic export of mRNAs. The promoter and terminator combination affects gene expression. In the present article, we review the function and features of plant core promoters, proximal and distal promoters, and terminators, and their effects on and benchmarking strategies for regulating gene expression.

Abstract The scope and variety of the metabolic intermediates from the mitochondrial tricarboxylic acid (TCA) cycle that are engaged in epigenetic regulation of the chromatin function in the nucleus raise an outstanding question about how timely and precise supply/consumption of these metabolites is achieved in the nucleus. We report here the identification of a nonclassical TCA cycle in the nucleus (nTCA cycle). We found that all the TCA cycle-associated enzymes including citrate synthase (CS), aconitase 2 (ACO2), isocitrate dehydrogenase 3 (IDH3), oxoglutarate dehydrogenase (OGDH), succinyl-CoA synthetase (SCS), fumarate hydratase (FH), and malate dehydrogenase 2 (MDH2), except for succinate dehydrogenase (SDH), a component of electron transport chain for generating ATP, exist in the nucleus. We showed that these nuclear enzymes catalyze an incomplete TCA cycle similar to that found in cyanobacteria. We propose that the nTCA cycle is implemented mainly to generate/consume metabolic intermediates, not for energy production. We demonstrated that the nTCA cycle is intrinsically linked to chromatin dynamics and transcription regulation. Together, our study uncovers the existence of a nonclassical TCA cycle in the nucleus that links the metabolic pathway to epigenetic regulation.

In this paper, the heating system of the airport energy station is taken as the research object. Aiming at the existing scheduling strategy of multi-heat-source heating system is difficult to achieve the optimal system working condition on the premise of meeting the needs of users. An intelligent scheduling strategy based on an improved FWA is studied. Firstly, the multi-heat-source heating system is analyzed, and the energy consumption model of operating equipment is established. According to the actual situation of the equipment, the multi-objective scheduling model is established. Then, the improved multi-objective fireworks algorithm is studied, including the initialization definition method of fireworks operator, the calculation method of fitness, mutation operator, the calculation method of explosion spark radius, and the concept of Pareto solution set in genetic algorithm with elite strategy is introduced. Finally, a multi-objective optimization function is established to minimize the equipment operation cost and heat source cost, and the multi-objective optimization problem is solved. Compared with the existing airport energy station dispatching scheme, the total operation cost of the optimized system is saved about 28.44%, and the energy waste is reduced based on the excellent operation of the heating system, achieved the optimal working condition

Numerous studies have demonstrated that type 2 diabetes (T2D) is closely linked to the occurrence of Alzheimer’s disease (AD). Nevertheless, the underlying mechanisms for this association are still unknown. Insulin resistance (IR) hallmarked by hyperinsulinemia, as the earliest and longest-lasting pathological change in T2D, might play an important role in AD. Since hyperinsulinemia has an independent contribution to related disease progressions by promoting inflammation in the peripheral system, we hypothesized that hyperinsulinemia might have an effect on microglia which plays a crucial role in neuroinflammation of AD. In the present study, we fed 4-week-old male C57BL/6 mice with a high-fat diet (HFD) for 12 weeks to establish IR model, and the mice treated with standard diet (SD) were used as control. HFD led to obesity in mice with obvious glucose and lipid metabolism disorder, the higher insulin levels in both plasma and cerebrospinal fluid, and aberrant insulin signaling pathway in the whole brain. Meanwhile, IR mice appeared impairments of spatial learning and memory accompanied by neuroinflammation which was characterized by activated microglia and upregulated expression of pro-inflammatory factors in different brain regions. To clarify whether insulin contributes to microglial activation, we treated primary cultured microglia and BV2 cell lines with insulin in vitro to mimic hyperinsulinemia. We found that hyperinsulinemia not only increased microglial proliferation and promoted M1 polarization by enhancing the production of pro-inflammatory factors, but also impaired membrane translocation of glucose transporter 4 (GLUT4) serving as the insulin-responding glucose transporter in the processes of glucose up-taking, reduced ATP production and increased mitochondrial fission. Our study provides new perspectives and evidence for the mechanism underlying the association between T2D and AD.

Genogroup II genotype 4 (GII.4) norovirus causes acute gastroenteritis in children, and its infection is more severe than that of other genotypes. Early and precise detection and treatment are critical for controlling its spread and reducing the severity of infection. In this study, a rapid and efficient isothermal assay for the GII.4 norovirus detection (GII.4-CRISPR detection) was developed based on the CRISPR/Cas13a system. The assay can be applied without expensive instrumentation, and the results can be read via both fluorescence and lateral flow strip (LFS). The analytical sensitivity of this assay was 5 copies/reaction, and there was no cross-reaction with other genotypes of norovirus or other clinically common pathogens. There was a coincidence rate of 100% between our assay and commercial quantitative polymerase chain reaction. GII.4-CRISPR detection improves upon the shortcomings of some previously established molecular methods of detection, particularly with regard to accessibility. It provides an alternative tool for outbreak control and early diagnosis of GII.4 norovirus infection.

Abstract Woody biomass is an important feedstock for biofuel production. Manipulation of wood properties that enable efficient conversion of biomass to biofuel reduces cost of biofuel production. Wood cell wall composition is regulated at several levels that involve expression of transcription factors such as wood‐/secondary cell wall‐associated NAC domains (WND or SND). In Arabidopsis thaliana, SND1 regulates cell wall composition through activation of its down‐stream targets such as MYBs. The functional aspects of SND1 homologs in the woody Populus have been studied through transgenic manipulation. In this study, we investigated the role of PdWND1B, Populus SND1 sequence ortholog, in wood formation using transgenic manipulation through over‐expression or silencing under the control of a vascular‐specific 4‐coumarate‐CoA ligase (4CL) promoter. As compared with control plants, PdWND1B‐RNAi plants were shorter in height, with significantly reduced stem diameter and dry biomass, whereas there were no significant differences in growth and productivity of PdWND1B over‐expression plants. Conversely, PdWND1B over‐expression lines showed a significant reduction in cellulose and increase in lignin content, whereas there was no significant impact on lignin content of downregulated lines. Stem carbohydrate composition analysis revealed a decrease in glucose, mannose, arabinose, and galactose, but an increase in xylose in the over‐expression lines. Transcriptome analysis revealed upregulation of several downstream transcription factors and secondary cell wall related structural genes in the PdWND1B over‐expression lines, partly explaining the observed phenotypic changes in cell wall chemistry. Relative to the control, glucose release efficiency and ethanol production from stem biomass was significantly reduced in over‐expression lines. Our results show that PdWND1B is an important factor determining biomass productivity, cell wall chemistry and its conversion to biofuels in Populus.

The white spot syndrome virus is the most destructive virus threatening the shrimp industry worldwide, causing hundreds of millions of dollars in economic losses each year. There is currently no specific medicine to treat it. Therefore, rapid and accurate detection of WSSV is of great significance for controlling its spread and reducing economic losses. Traditional detection methods, such as polymerase chain reaction (PCR) and quantitative fluorescent PCR, rely on laboratory equipment and are not suitable for field testing. In this study, recombinase polymerase amplification (RPA) combined with a lateral flow strip (LFS) was developed. This method targets the entire genome and designs primers and probes accordingly. The detection can be completed in 30 min at 37°C, and the detection limit of each reaction is 20 copies, which is much more sensitive than other detection methods. The RPA-LFS method is highly specific to the white spot syndrome virus and has no cross-reactivity with other common shrimp viruses or pathogens. In total, 100 field samples were tested and compared to the real-time PCR method. Both methods detected 8 positive results, and the positive detection rate was 100%. The method was fast, simple, specific, and sensitive. It does not rely on laboratory equipment and has broad application prospects for in-field detection, especially in remote areas with underdeveloped medical equipment.

Although CRISPR/Cas-based genome editing has been widely used for plant genetic engineering, its application in the genetic improvement of trees has been limited, partly because of challenges in Agrobacterium-mediated transformation. As an important model for poplar genomics and biotechnology research, eastern cottonwood (Populus deltoides) clone WV94 can be transformed by A. tumefaciens, but several challenges remain unresolved, including the relatively low transformation efficiency and the relatively high rate of false positives from antibiotic-based selection of transgenic events. Moreover, the efficacy of CRISPR-Cas system has not been explored in P. deltoides yet. Here, we first optimized the protocol for Agrobacterium-mediated stable transformation in P. deltoides WV94 and applied a UV-visible reporter called eYGFPuv in transformation. Our results showed that the transgenic events in the early stage of transformation could be easily recognized and counted in a non-invasive manner to narrow down the number of regenerated shoots for further molecular characterization (at the DNA or mRNA level) using PCR. We found that approximately 8.7% of explants regenerated transgenic shoots with green fluorescence within two months. Next, we examined the efficacy of multiplex CRISPR-based genome editing in the protoplasts derived from P. deltoides WV94 and hybrid poplar clone ‘52-225’ (P. trichocarpa × P. deltoides clone ‘52-225’). The two constructs expressing the Trex2-Cas9 system resulted in mutation efficiency ranging from 31% to 57% in hybrid poplar clone 52-225, but no editing events were observed in P. deltoides WV94 transient assay. The eYGFPuv-assisted plant transformation and genome editing approach demonstrated in this study has great potential for accelerating the genome editing-based breeding process in poplar and other non-model plants species and point to the need for additional CRISPR work in P. deltoides.

There is currently a lack of sufficient data on human papillomavirus (HPV)-attributable cervical carcinoma in China. Accordingly, we aimed to determine the prevalence and genotype distribution of HPV among women with cervical lesions in Shenzhen, in order to evaluate the potential benefit of HPV vaccination programs and inform cervical cancer control policies. We enrolled 5,255 patients who were admitted to the University of Chinese Academy of Sciences Shenzhen Hospital from January 2017 to December 2019. The HPV prevalence and genotype distribution were analyzed using the 21 HPV GenoArray diagnostic assay. A total of 937/5,255 patients showed HPV-positivity (prevalence rate 17.83%), of whom 85.81% (804/937) had high-risk HPV infection. HPV52 was the most prevalent genotype (4.72%, 248/5,255), followed by HPV58 (3.04%, 160/5,255), and HPV16 (2.72%, 143/5,255). The HPV prevalence rates among women with a normal cervix, low-grade intraepithelial lesions, high-grade intraepithelial lesions, invasive cervical cancer, and other characteristics were 15.63% (50/320), 58.65% (61/104), 80.00% (44/55), 88.57% (31/35), and 15.84% (751/4,741), respectively. HPV16, HPV18, and HPV52 accounted for the majority of cervical lesions, and the infection rates of HPV16 and HPV18 gradually increased with intraepithelial lesion progression (both P

Abstract Previous genome-wide association studies (GWAS) have identified potential genetic variants associated with the risk of major depressive disorder (MDD), but the underlying biological interpretation remains largely unknown. We aimed to prioritize genes that were pleiotropically or potentially causally associated with MDD. We applied the summary data-based Mendelian randomization (SMR) method integrating GWAS and gene expression quantitative trait loci (eQTL) data in 13 brain regions to identify genes that were pleiotropically associated with MDD. In addition, we repeated the analysis by using the meta-analyzed version of the eQTL summary data in the brain (brain-eMeta). We identified multiple significant genes across different brain regions that may be involved in the pathogenesis of MDD. The prime-specific gene BTN3A2 (corresponding probe: ENSG00000186470.9) was the top hit showing pleiotropic association with MDD in 9 of the 13 brain regions and in brain-eMeta, after correction for multiple testing. Many of the identified genes are located in the human major histocompatibility complex (MHC) region on chromosome 6 and are mainly involved in the immune response. Our SMR analysis indicated that multiple genes showed pleiotropic association with MDD across the brain regions. These findings provided important leads to a better understanding of the mechanism of MDD and revealed potential therapeutic targets for the prevention and effective treatment of MDD.

Lysine crotonylation is a protein post-translational modification that has been newly discovered in recent years. There are few studies on the lysine crotonylation of proteins in plants, and their functions in response to cold stress are still unclear. In this study, the chrysanthemum (Chrysanthemum morifolium Ramat.) glutathione peroxidase (GPX) gene was selected and named DgGPX1, and was found to be responsive to low temperature. Overexpression of DgGPX1 improved the cold resistance of transgenic chrysanthemum by increasing GPX activity to reduce the accumulation of reactive oxygen species (ROS) under low-temperature conditions. Furthermore, the level of DgGPX1 lysine crotonylation at lysine (K) 220 decreased under low temperature in chrysanthemum. Lysine decrotonylation of DgGPX1 at K220 further increased GPX activity to reduce ROS accumulation under cold stress, and thereby enhanced the cold resistance of chrysanthemum. The above results show that lysine decrotonylation of DgGPX1 at K220 increases GPX activity to resist cold stress in chrysanthemum.

Shrub willows (Salix section Vetrix) are grown as a bioenergy crop in multiple countries and as ornamentals across the northern hemisphere. To facilitate the breeding and genetic advancement of shrub willow, there is a strong interest in the characterization and functional validation of genes involved in plant growth and biomass production. While protocols for shoot regeneration in tissue culture and production of stably transformed lines have greatly advanced this research in the closely related genus Populus, a lack of efficient methods for regeneration and transformation has stymied similar advancements in willow functional genomics. Moreover, transient expression assays in willow have been limited to callus tissue and hairy root systems. Here we report an efficient method for protoplast isolation from S. purpurea leaf tissue, along with transient overexpression and CRISPR-Cas9 mediated mutations. This is the first such report of transient gene expression in Salix protoplasts as well as the first application of CRISPR technology in this genus. These new capabilities pave the way for future functional genomics studies in this important bioenergy and ornamental crop.

Egress of flaviviruses and involved host pathways are not well understood. Here, the authors show that Lyn is a critical host kinase for Dengue and Zika virus egress resulting in infectious virus progenies within autophagosome-derived vesicles, which might help the virus to evade antibody responses.

Plants adapt to their changing environments by sensing and responding to physical, biological, and chemical stimuli. Due to their sessile lifestyles, plants experience a vast array of external stimuli and selectively perceive and respond to specific signals. By repurposing the logic circuitry and biological and molecular components used by plants in nature, genetically encoded plant-based biosensors (GEPBs) have been developed by directing signal recognition mechanisms into carefully assembled outcomes that are easily detected. GEPBs allow for in vivo monitoring of biological processes in plants to facilitate basic studies of plant growth and development. GEPBs are also useful for environmental monitoring, plant abiotic and biotic stress management, and accelerating design-build-test-learn cycles of plant bioengineering. With the advent of synthetic biology, biological and molecular components derived from alternate natural organisms (e.g., microbes) and/or de novo parts have been used to build GEPBs. In this review, we summarize the framework for engineering different types of GEPBs. We then highlight representative validated biological components for building plant-based biosensors, along with various applications of plant-based biosensors in basic and applied plant science research. Finally, we discuss challenges and strategies for the identification and design of biological components for plant-based biosensors.

Atherosclerosis is the major pathophysiological basis of cerebrovascular and cardiovascular diseases. Vascular smooth muscle cells (VSMCs) constitute the main structure of vasculature and play important roles in maintaining vascular tone and blood pressure. Many biological processes and cellular signaling events involved in atherosclerogenesis have been shown to converge on deregulating VSMC functions. However, the molecular mechanisms underlying dysfunctional VSMC in atherosclerosis are still poorly defined. Recent evidence revealed that circular RNAs (circRNAs) are closely related to diseases such as degenerative diseases, tumor, congenital diseases, endocrine diseases and cardiovascular diseases. Several studies demonstrated that circRNAs (e.g., circACTA2, Circ-SATB2, circDiaph3, circ_0020397, circTET3, circCCDC66) played critical roles in the regulation of VSMC proliferation, migration, invasion, and contractile-to-synthetic phenotype transformation by sponging microRNAs (e.g., miR-548f-5p, miR-939, miR-148a-5p, miR-138, miR-351-5p, miR-342-3p). This review describes recent progress in the profiling of circRNAs by transcriptome analysis in VSMCs and their molecular functions in regulating VSMC proliferation and migration.

Abstract Background Plant secondary cell wall is a renewable feedstock for biofuels and biomaterials production. Arabidopsis VASCULAR-RELATED NAC DOMAIN (VND) has been demonstrated to be a key transcription factor regulating secondary cell wall biosynthesis. However, less is known about its role in the woody species. Results Here we report the functional characterization of Populus deltoides WOOD-ASSOCIATED NAC DOMAIN protein 3 (PdWND3A), a sequence homolog of Arabidopsis VND4 and VND5 that are members of transcription factor networks regulating secondary cell wall biosynthesis. PdWND3A was expressed at higher level in the xylem than in other tissues. The stem tissues of transgenic P. deltoides overexpressing PdWND3A (OXPdWND3A) contained more vessel cells than that of wild-type plants. Furthermore, lignin content and lignin monomer syringyl and guaiacyl (S/G) ratio were higher in OXPdWND3A transgenic plants than in wild-type plants. Consistent with these observations, the expression of FERULATE 5-HYDROXYLASE1 (F5H1), encoding an enzyme involved in the biosynthesis of sinapyl alcohol (S unit monolignol), was elevated in OXPdWND3A transgenic plants. Saccharification analysis indicated that the rate of sugar release was reduced in the transgenic plants. In addition, OXPdWND3A transgenic plants produced lower amounts of biomass than wild-type plants. Conclusions PdWND3A affects lignin biosynthesis and composition and negatively impacts sugar release and biomass production.

Plants with crassulacean acid metabolism (CAM) generally utilize water 20%–80% more efficiently than non-CAM plants. The whole genomes of several CAM plants have been sequenced or are being sequenced. For effective genome characterization and genome editing of CAM plants, an efficient transformation system is essential. In this study, we developed an Agrobacterium-mediated transformation protocol for Kalanchoe laxiflora, an obligate CAM plant,by optimizing several factors affecting the transformation efficiency. Agrobacterium strains AGL1, C58, EHA105, and GV3101 were all suitable for K. laxiflora transformation. Fifty-nine percent of the leaf explants yielded kanamycin-resistant and GUS-positive shoots. Polymerase chain reaction and quantitative real-time PCR (qRT-PCR) using gusA-, gusPlus-, nptII- and hpt-specific primers confirmed that the transgenes were integrated into K. laxiflora genome and expressed. This efficient transformation system will allow effective functional characterization of genes through over- or down-expression, knockout, or genome editing. Keywords: Kalanchoe laxiflora, Agrobacterium-mediated transformation, CAM plants

Unlike past health crises that were more localized, the highly contagious coronavirus disease 2019 (COVID-19) crisis is impacting the world to an unprecedented extent. This is the first study examining how and whether the COVID-19 pandemic affects herding behavior in the Eastern European stock markets. Using samples from the stock markets of Russia, Poland, the Czech Republic, Hungary, Croatia, and Slovenia from January 1, 2010 to March 10, 2021, we demonstrate that the COVID-19 pandemic has increased herding behavior in all the sample stock markets. Our results show that the COVID-19 crisis reinforces the impact of global market returns on herding behavior in these specific stock markets. We find that COVID-19 strengthens the spillover effect of regional herding on herding behavior. Thus, financial authorities should monitor investors in the stock market to avoid the increase in herding behavior as well as the reinforcement of the global market returns and regional return dispersion on herding during the period of pandemic.

A continuous increase in ambient temperature caused by global warming has been considered a worldwide threat. As sessile organisms, plants have evolved sophisticated heat shock response (HSR) to respond to elevated temperatures and other abiotic stresses, thereby minimizing damage and ensuring the protection of cellular homeostasis. In particular, for perennial trees, HSR is crucial for their long life cycle and development. HSR is a cell stress response that increases the number of chaperones including heat shock proteins (HSPs) to counter the negative effects on proteins caused by heat and other stresses. There are a large number of HSPs in plants, and their expression is directly regulated by a series of heat shock transcription factors (HSFs). Therefore, understanding the detailed molecular mechanisms of woody plants in response to extreme temperature is critical for exploring how woody species will be affected by climate changes. In this review article, we summarize the latest findings of the role of HSFs and HSPs in the HSR of woody species and discuss their regulatory networks and cross talk in HSR. In addition, strategies and programs for future research studies on the functions of HSFs and HSPs in the HSR of woody species are also proposed.

Multiplexed CRISPR technologies have great potential for pathway engineering and genome editing. However, their applications are constrained by complex, laborious and time-consuming cloning steps. In this research, we developed a novel method, PARA, which allows for the one-step assembly of multiple guide RNAs (gRNAs) into a CRISPR vector with up to 18 gRNAs. Here, we demonstrate that PARA is capable of the efficient assembly of transfer RNA/Csy4/ribozyme-based gRNA arrays. To aid in this process and to streamline vector construction, we developed a user-friendly PARAweb tool for designing PCR primers and component DNA parts and simulating assembled gRNA arrays and vector sequences.

Agave angustifolia is an important crassulacean acid metabolism plant species, with wide applications in beverage and sisal fiber production. In this study, we carried out a transcriptome analysis of A. angustifolia leaves, generating a total of 58,482,436 clean reads through Illumina paired-end sequencing. De novo transcriptome assembly generated 67,314 unigenes, with about half of them having homologs in four public databases. In the Nr database, Asparagus officinalis was shown to be most closely related to agave, and the early angiosperm Amborella trichopoda was selected as an outgroup species. We further identified five, two, seven, seven, seven, six and six CAD genes in asparagus, amborella, A. deserti, A. tequilana, A. americana, A. hybrid H11648 and A. angustifolia, respectively. The maximum likelihood phylogenetic tree revealed the species-specific expansion of CAD genes in arabidopsis, rice and agave. The expression analysis indicated the conservatively expressed CAD1/2/4/6, providing candidate targets for manipulation to improve lignin traits. The species-specific expression of CAD3/5/7 indicates the existence of different regulatory mechanisms controlling the expression of these genes in agave species. This study presents the first transcriptome dataset of A. angustifolia, facilitating future studies on lignin biosynthesis in agave.

The cross-modal retrieval task can return different modal nearest neighbors, such as image or text. However, inconsistent distribution and diverse representation make it hard to directly measure the similarity relationship between different modal samples, which causes a heterogeneity gap. To bridge the above-mentioned gap, we propose the deep adversarial learning triplet similarity preserving cross-modal retrieval algorithm to map different modal samples into the common space, allowing their feature representation to preserve both the original inter- and intra-modal semantic similarity relationship. During the training process, we employ GANs, which has advantages in modeling data distribution and learning discriminative representation, in order to learn different modal features. As a result, it can align different modal feature distributions. Generally, many cross-modal retrieval algorithms only preserve the inter-modal similarity relationship, which makes the nearest neighbor retrieval results vulnerable to noise. In contrast, we establish the triplet similarity preserving function to simultaneously preserve the inter- and intra-modal similarity relationship in the common space and in each modal space, respectively. Thus, the proposed algorithm has a strong robustness to noise. In each modal space, to ensure that the generated features have the same semantic information as the sample labels, we establish a linear classifier and require that the generated features’ classification results be consistent with the sample labels. We conducted cross-modal retrieval comparative experiments on two widely used benchmark datasets—Pascal Sentence and Wikipedia. For the image to text task, our proposed method improved the mAP values by 1% and 0.7% on the Pascal sentence and Wikipedia datasets, respectively. Correspondingly, the proposed method separately improved the mAP values of the text to image performance by 0.6% and 0.8% on the Pascal sentence and Wikipedia datasets, respectively. The experimental results show that the proposed algorithm is better than the other state-of-the-art methods.

The image-text cross-modal retrieval task, which aims to retrieve the relevant image from text and vice versa, is now attracting widespread attention. To quickly respond to the large-scale task, we propose an Unsupervised Deep Relative Neighbor Relationship Preserving Cross-Modal Hashing (DRNPH) to achieve cross-modal retrieval in the common Hamming space, which has the advantages of storage and efficiency. To fulfill the nearest neighbor search in the Hamming space, we demand to reconstruct both the original intra- and inter-modal neighbor matrix according to the binary feature vectors. Thus, we can compute the neighbor relationship among different modal samples directly based on the Hamming distances. Furthermore, the cross-modal pair-wise similarity preserving constraint requires the similar sample pair have an identical Hamming distance to the anchor. Therefore, the similar sample pairs own the same binary code, and they have minimal Hamming distances. Unfortunately, the pair-wise similarity preserving constraint may lead to an imbalanced code problem. Therefore, we propose the cross-modal triplet relative similarity preserving constraint, which demands the Hamming distances of similar pairs should be less than those of dissimilar pairs to distinguish the samples’ ranking orders in the retrieval results. Moreover, a large similarity marginal can boost the algorithm’s noise robustness. We conduct the cross-modal retrieval comparative experiments and ablation study on two public datasets, MIRFlickr and NUS-WIDE, respectively. The experimental results show that DRNPH outperforms the state-of-the-art approaches in various image-text retrieval scenarios, and all three proposed constraints are necessary and effective for boosting cross-modal retrieval performance.

Summary: Exploitation of naturally occurring genetic mutations could empower the discovery of novel aspects of established cancer genes. We report here that TRPS1, a gene linked to the tricho-rhino-phalangeal syndrome (TRPS) and recently identified as a potential breast cancer driver, promotes breast carcinogenesis through regulating replication. Epigenomic decomposition of TRPS1 landscape reveals nearly half of H3K9me3-marked heterochromatic origins are occupied by TRPS1, where it encourages the chromatin loading of APC/C, resulting in uncontrolled origin refiring. TRPS1 binds to the genome through its atypical H3K9me3 reading via GATA and IKAROS domains, while TRPS-related mutations affect its chromatin binding, replication boosting, and tumorigenicity. Concordantly, overexpression of wild-type but not TRPS-associated mutants of TRPS1 is sufficient to drive cancer genome amplifications, which experience an extrachromosomal route and dynamically evolve to confer therapeutic resistance. Together, these results uncover a critical function of TRPS1 in driving heterochromatin origin firing and breast cancer genome evolution.

Plant drought stress causes systematic changes to photosynthesis, metabolism, growth, and potentially the phytobiome. Additionally, drought affects plants in both a species-specific and water-deficit-driven manner, causing the response to drought to be dependent both on how drought is being experienced and on any adaptation to prior drought exposure. Thus, understanding the effect of drought on plants requires assessing drought response in multiple conditions, such as progressive acute drought and recurrent cyclic drought, and at different levels of severity. In this study, we have utilized RNA sequencing to identify changes to the plant transcriptome and the phytobiome during both acute progressive drought and cyclic drought at multiple severities. Co-analysis of the plant and phytobiome, utilizing the same RNAseq data, allows for the identification of novel associations that would not be possible otherwise. We have identified that the drought response ranges from increased transcripts related to photosynthesis and metabolic activity in mild acute drought to decreased transcripts related to photosynthesis and metabolic impairment in severe drought. Moreover, while water deficit is a main driver of transcriptional responses in severe drought, there are increases in reactive oxygen species (ROS) metabolism and photosynthetic transcripts in cyclic severe drought compared with acute severe drought, independent of water deficit. The phytobiome exhibits alternate responses to drought when compared with the transcriptome. Specifically, the phytobiome is affected more by the cyclic or acute nature of the drought rather than the severity of the drought, with the phytobiome having an increase in taxa under cyclic drought that are often reported to have beneficial effects on the plants. Lastly, we have identified associations between taxa in the phytobiome with expression of disease response, ROS metabolism, and photosynthesis transcripts suggesting interplay between the host plant and its phytobiome in response to drought.

Blind image quality assessment (BIQA) methods aim to predict quality of images as perceived by humans without access to a reference image. Recently, deep learning methods have gained substantial attention in the research community and have proven useful for BIQA. Although previous study of deep neural networks (DNN) methods is presented, some novelty DNN methods, which are recently proposed, are not summarized for BIQA. In this paper, we provide a survey covering various DNN methods for BIQA. First, we systematically analyze the existing DNN-based quality assessment methods according to the role of DNN. Then, we compare the prediction performance of various DNN methods on the synthetic databases (LIVE, TID2013, CSIQ, LIVE multiply distorted) and authentic databases (LIVE challenge), providing important information that can help understand the underlying properties between different DNN methods for BIQA. Finally, we describe some emerging challenges in designing and training DNN-based BIQA, along with few directions that are worth further investigations in the future.

Abstract Background Microglia-derived lysosomal cathepsins are important inflammatory mediators to trigger signaling pathways in inflammation-related cascades. Our previous study showed that the expression of cathepsin C (CatC) in the brain is induced predominantly in activated microglia in neuroinflammation. Moreover, CatC can induce chemokine production in brain inflammatory processes. In vitro studies further confirmed that CatC is secreted extracellularly from LPS-treated microglia. However, the mechanisms of CatC affecting neuroinflammatory responses are not known yet. Methods CatC over-expression (CatCOE) and knock-down (CatCKD) mice were treated with intraperitoneal and intracerebroventricular LPS injection. Morris water maze (MWM) test was used to assess the ability of learning and memory. Cytokine expression in vivo was detected by in situ hybridization, quantitative PCR, and ELISA. In vitro, microglia M1 polarization was determined by quantitative PCR. Intracellular Ca2+ concentration was determined by flow cytometry, and the expression of NR2B, PKC, p38, IkBα, and p65 was determined by western blotting. Results The LPS-treated CatCOE mice exhibited significantly increased escape latency compared with similarly treated wild-type or CatCKD mice. The highest levels of TNF-α, IL-1β, and other M1 markers (IL-6, CD86, CD16, and CD32) were found in the brain or serum of LPS-treated CatCOE mice, and the lowest levels were detected in CatCKD mice. Similar results were found in LPS-treated microglia derived from CatC differentially expressing mice or in CatC-treated microglia from wild-type mice. Furthermore, the expression of NR2B mRNA, phosphorylation of NR2B, Ca2+ concentration, phosphorylation of PKC, p38, IκBα, and p65 were all increased in CatC-treated microglia, while addition of E-64 and MK-801 reversed the phosphorylation of above molecules. Conclusion The data suggest that CatC promotes microglia M1 polarization and aggravates neuroinflammation via activation of Ca2+-dependent PKC/p38MAPK/NF-κB pathway. CatC may be one of key molecular targets for alleviating and controlling neuroinflammation in neurological diseases.