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Abstract Background Existing literature on the impact of lipid accumulation product (LAP) and visceral adiposity index (VAI) on severe headache or migraine is limited. This study aims to elucidate the association between LAP and VAI and the prevalence of migraine. Methods Data for this study were sourced from the 1999–2004 National Health and Nutrition Examination Survey (NHANES). A database-self-administered questionnaire was used to assess severe headache or migraine. A weighted logistic regression model was employed to assess the relationship between LAP and VAI with migraine prevalence. Complementary analytical approaches included subgroup analysis, restricted cubic spline (RCS), and threshold effect analysis to validate the findings. Results In the end, 4572 people were recruited for the research, including 880 with migraine and 3692 without migraine. Following adjustment for the relevant covariables, weighted logistic regression analysis (OR = 1.409, 95% CI: 1.054, 1.883, P = 0.022; OR = 1.288, 95% CI: 1.010, 1.642, P = 0.042) revealed significantly elevated odds of migraine prevalence in participants within the highest tertile (T3) of LAP and VAI than those in the lowest tertile (T1). The nonlinear association between migraine prevalence and both VAI and LAP was further elucidated through a restricted cubic spline. The threshold analysis pinpointed 2.142 (log-likelihood ratio = 0.016) as the critical inflection point for VAI. Subgroup analysis and interaction testing revealed the significant association was independent in different subgroup factors. Conclusions The data indicate a robust association between higher levels of LAP and VAI and an increased prevalence of migraine.

Many soils face dual challenges of cadmium (Cd) contamination and salinization. However, the response of crops, especially wheat, to combined Cd and salinity stress is not understood. Here, wheat was grown in a hydroponic model for 14 days under single and combined Cd and NaCl stresses. Growth parameters, tissue Cd2+ and Na+ contents, and leaf chlorophyll (Chl), O2•−, and MDA levels were determined. Comparative transcriptomic and metabolomic analyses of the leaves were performed. The results showed that combined stress had a greater inhibitory effect on Chl contents and generated more O2•− and MDA, resulting in more severe wheat growth retardation than those under Cd or NaCl stress. Stress-induced decrease in Chl levels may be attributed to the inhibition of Chl biosynthesis, activation of Chl degradation, or a decline in glutamate content. Cd addition weakened the promotional effect of NaCl on SOS1 gene expression, thereby increasing the Na+ content. Contrastingly, NaCl supplementation downregulated the Nramp and ZIP gene expressions related to Cd uptake and transport, thereby impeding Cd2+ accumulation. All stresses enhanced tryptophan content via promoting tryptophan biosynthesis. Meanwhile, Cd and NaCl stresses activated phenylpropanoid biosynthesis and purine metabolism, respectively, thereby increasing the levels of caffeic acid, fumaric acid, and uric acid. Activating the TCA cycle was important in the wheat’s response to combined stress. Additionally, NaCl and combined stresses affected starch and sucrose metabolism, resulting in sucrose and trehalose accumulation. Our findings provide a comprehensive understanding of the response of wheat to the combined Cd and salinity stress.

Objective: Noise exposure limit is one of the critical measures to prevent noise-induced hearing loss (NIHL). This review aimed to review the progress and recommendations for developing occupational exposure limits (OELs) for workplace noise. Methods: A systematic review was used. Thirty-eight national or international organizations' noise exposure standards (including OEL) and laws, regulations, and guidelines for noise exposure control were analyzed. Articles on recommendations for revising noise OEL standards between 2000 and 2023 were selected. Results: The definition of different noise types (especially for non-steady and impulsive noise) varied worldwide, and the used 8-h OEL varied from 80 to 90 dB(A). Maximum sound pressure level (Lmax) and noise dose for industrial noise and peak sound pressure level (Lpeak) for impulsive noise have been incorporated into the OELs. Countries developed noise risk management measures based on OELs, action levels (ALs), and exposure risk ratio or classification. The risk of co-exposure to noise and ototoxic organic substances and the effects of noise on susceptible populations were concerns in EU country standards. Scholars suggested revising the existing noise exposure standards based on noise's temporal structure (expressed by kurtosis), effective noise level, impulsive noise OEL, action level, and key factors of risk assessment. Conclusions: Indicators such as Lmax, noise dose, Lpeak, and action level can be incorporated into noise OELs. Developing noise OEL standards should consider the co-exposure of noise and ototoxic substances, HPD's noise attenuation, susceptible groups, and noise's temporal structure.

The pathogenesis of membranous nephropathy (MN) involves podocyte injury that is attributed to inflammatory responses induced by local immune deposits. Astragaloside IV (AS-IV) is known for its robust anti-inflammatory properties. Here, we investigated the effects of AS-IV on passive Heymann nephritis (PHN) rats and TNF-α-induced podocytes to determine the underlying molecular mechanisms of MN. Serum biochemical parameters, 24-h urine protein excretion and renal histopathology were evaluated in PHN and control rats. The expression of tumor necrosis factor receptor associated factor 6 (TRAF6), the phosphorylation of nuclear factor kappa B (p-NF-κB), the expression of associated proinflammatory cytokines (TNF-α, IL-6 and IL-1β) and the ubiquitination of TRAF6 were measured in PHN rats and TNF-α-induced podocytes. We detected a marked increase in mRNA expression of TNF-α, IL-6 and IL-1β and in the protein abundance of p-NF-κB and TRAF6 within the renal tissues of PHN rats and TNF-α-induced podocytes. Conversely, there was a reduction in the K48-linked ubiquitination of TRAF6. Additionally, AS-IV was effective in ameliorating serum creatinine, proteinuria, and renal histopathology in PHN rats. This effect was concomitant with the suppression of NF-κB pathway activation and decreased expression of TNF-α, IL-6, IL-1β and TRAF6. AS-IV decreased TRAF6 levels by promoting K48-linked ubiquitin conjugation to TRAF6, which triggered ubiquitin-mediated degradation. In summary, AS-IV averted renal impairment in PHN rats and TNF-α-induced podocytes, likely by modulating the inflammatory response through the TRAF6/NF-κB axis. Targeting TRAF6 holds therapeutic promise for managing MN.

IntroductionInherited retinal diseases (IRDs) affect ∼4.5 million people worldwide. Elusive pathogenic variants in over 280 genes are associated with one or more clinical forms of IRDs. It is necessary to understand the complex interaction among retinal cell types and pathogenic genes by constructing a regulatory network. In this study, we attempt to establish a panoramic expression view of the cooperative work in retinal cells to understand the clinical manifestations and pathogenic bases underlying IRDs.MethodsSingle-cell RNA sequencing (scRNA-seq) data on the retinas from 35 retina samples of 3 species (human, mouse, and zebrafish) including 259,087 cells were adopted to perform a comparative analysis across species. Bioinformatic tools were used to conduct weighted gene co-expression network analysis (WGCNA), single-cell regulatory network analysis, cell–cell communication analysis, and trajectory inference analysis.ResultsThe cross-species comparison revealed shared or species-specific gene expression patterns at single-cell resolution, such as the stathmin family genes, which were highly expressed specifically in zebrafish Müller glias (MGs). Thirteen gene modules were identified, of which nine were associated with retinal cell types, and Gene Ontology (GO) enrichment of module genes was consistent with cell-specific highly expressed genes. Many IRD genes were identified as hub genes and cell-specific regulons. Most IRDs, especially the retinitis pigmentosa (RP) genes, were enriched in rod-specific regulons. Integrated expression and transcription regulatory network genes, such as congenital stationary night blindness (CSNB) genes GRK1, PDE6B, and TRPM1, showed cell-specific expression and transcription characteristics in either rods or bipolar cells (BCs). IRD genes showed evolutionary conservation (GNAT2, PDE6G, and SAG) and divergence (GNAT2, MT-ND4, and PDE6A) along the trajectory of photoreceptors (PRs) among species. In particular, the Leber congenital amaurosis (LCA) gene OTX2 showed high expression at the beginning of the trajectory of both PRs and BCs.ConclusionWe identified molecular pathways and cell types closely connected with IRDs, bridging the gap between gene expression, genetics, and pathogenesis. The IRD genes enriched in cell-specific modules and regulons suggest that these diseases share common etiological bases. Overall, mining of interspecies transcriptome data reveals conserved transcriptomic features of retinas across species and promising applications in both normal retina anatomy and retina pathology.

Within the context of contemporary society, the propagation of information is often subject to the influence of inter-individual connectivity, and individuals may exhibit divergent receptive attitudes towards identical information, a phenomenon denoted as the Hesitant-Common (HECO) trait. In light of this, the present study initially constructs a propagation network model devoid of correlation configurations to investigate the HECO characteristics within weighted social networks. Subsequently, the study employs a theoretical framework for edge partitioning, predicated on edge weights and HECO traits, to quantitatively analyze the mechanisms of individual information dissemination. Theoretical analyses and simulation outcomes consistently demonstrate that an augmentation in the proportion of common individuals facilitates both the diffusion and adoption of information. Concurrently, a phase transition crossover is observed, wherein the growth pattern of the ultimate adoption range, denoted as R(∞), transitions from a first-order discontinuous phase transition to a second-order continuous phase transition as the proportion of common individuals increases. An escalation in the weight distribution exponent is found to enhance information propagation. Furthermore, a reduction in the heterogeneity of degree distribution is conducive to the spread of information. Conversely, an increase in degree distribution heterogeneity and a diminution in the collective decision-making capacity can both exert inhibitory effects on the propagation of information.

Abstract In stark contrast to adult patients, children who contract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) typically manifest milder symptoms or remain asymptomatic. However, the precise underlying mechanisms of this pathogenesis remain elusive. In this review, we primarily retrospect the clinical characteristics of SARS-CoV-2 infection in children, and explore the factors that may contribute to the typically milder clinical presentation in pediatric Coronavirus Disease 2019 (COVID-19) patients compare with adults patients with COVID-19. The pathophysiological mechanisms that mitigate lung injury in children are as follows: the expression level of ACE2 receptor in children is lower; the binding affinity between ACE2 receptors and viral spike proteins in children was weaker; children have strong pre-activated innate immune response and appropriate adaptive immune response; children have more natural lymphocytes; children with COVID-19 can produce higher levels of IgM, IgG and interferon; children infected with SARS-CoV-2 can produce lower levels of IL-6 and IL-10; children have fewer underlying diseases and the lower risk of worsening COVID-19; children are usually exposed to other respiratory viruses and have an enhanced cross-reactive immunity. Comprehending the relative contributions of these processes to the protective phenotype in the developing lungs can help in the diagnosis, treatment and research pertaining to children with COVID-19.

Psychological stress represents a prevalent societal concern, particularly evident during crises such as epidemics, which exacerbate various forms of psychological strain. Prompt mitigation of psychological stress holds potential for enhancing quality of life and fostering societal advancement. In this study, drawing inspiration from the International Emotion Picture Library, we crafted four virtual reality (VR) scenes augmented with five emblematic animals, resulting in 20 VR scenarios for psychological stress assessment. Fifteen participants engaged in the test, which was preceded by the completion of the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF). Throughout the test, EEG and heart rate data were meticulously recorded. Following each scenario, participants completed the Self-Assessment Manikin (SAM) scale, culminating in the formation of the VR psychological stress reduction dataset. We meticulously analyze the SAM scale. For EEG data, we devised a deep learning model leveraging a hybrid CNN-LSTM architecture for signal classification. The model was evaluated on both the publicly available DEAP dataset and our collected DSRP dataset, yielding superior performance. Leveraging the dataset amassed in this study, we scrutinize the alleviative impact of VR on human psychological stress, providing foundational insights for VR-based psychological stress reduction research. Moreover, the EEG classification model proposed herein enhances the categorization of EEG signals, thereby advancing the domain of emotion recognition grounded in EEG technology.

Change detection (CD) aims to identify surface changes from bitemporal remote sensing (RS) images, which is a crucial and challenging topic in RS. In recent years, RS images CD has achieved significant advancements through the use of convolutional neural networks. However, existing deep learning-based CD methods still face some challenges, such as blurry boundaries, pseudochanges caused by fluctuations in imaging conditions, and complexity of change objects in the scene. In this study, we present a novel perspective for exploring the cross-temporal interaction in the feature fusion stage and propose a bitemporal feature exchange and enhancement network (ExNet). Specifically, we argue that the heterogeneity of bitemporal RS images leads to the failure of the CD model in some cases. Therefore, we attempt to achieve feature alignment in two aspects by feature exchange. On one hand, we exchange the statistical information of bitemporal features, facilitating the transfer of their style. On the other hand, bitemporal features are composed of content correlation embeddings and domain correlation embeddings (DCEs). We design a dynamic low-pass filter (DLF) to partially extract and exchange DCEs in bitemporal features to achieve the feature distribution alignment. Moreover, a frequency separation enhancement module is proposed, which transforms the fused features into the frequency domain and enhances the corresponding frequency representation. Comprehensive experimental results on three popular CD datasets demonstrate the effectiveness and efficiency of ExNet compared with state-of-the-art methods.

Due to the coupling of multiple nonlinear factors in the position control system of the double closed-loop digital hydraulic cylinder, achieving precise and stable control of complex nonlinear systems with a single structural controller is difficult. To address this problem, we propose a Global Fast Terminal Sliding Mode Active Disturbance Rejection Control (GFTSMADRC). Firstly, by focusing on the mathematical model of the current double closed-loop digital hydraulic cylinder, the high-order nonlinear state equation of the system is derived, and employing active disturbance rejection control (ADRC), the high-order nonlinear system is transformed into a second-order integral series control system. Secondly, we propose Sliding Mode Active Disturbance Rejection Control (SMADRC) by integrating sliding mode variable structure control. Thirdly, to further enhance system performance, we propose a GFTSMADRC strategy by incorporating global fast terminal sliding mode variable structure control. The control law and adaptive law of the system are derived based on the Lyapunov stability theorem. Specifically, the effectiveness of the proposed control method is validated through simulation and experimentation.

Abstract Background Adipose-derived stem cells (ADSCs) have been extensively used in preclinical and clinical trials for treating various diseases. However, the differences between ADSCs from lean individuals (L-ADSCs) and those from obese individuals (O-ADSCs) have not been thoroughly investigated, particularly regarding their mitochondrial and lysosomal functions. Therefore, this study aims to evaluate the differences between L-ADSCs and O-ADSCs in terms of cell biological activity, mitochondria, and lysosomes. Methods We first isolated and cultured L-ADSCs and O-ADSCs. We then compared the differences between the two groups in terms of biological activity, including cell proliferation, differentiation potential, and their effect on the polarization of macrophages. Additionally, we observed the mitochondrial and lysosomal morphology of ADSCs using an electronic microscope, MitoTracker Red, and lysotracker Red dyes. We assessed mitochondrial function by examining mitochondrial membrane potential and membrane fluidity, antioxidative ability, and cell energy metabolism. Lysosomal function was evaluated by measuring autophagy and phagocytosis. Finally, we performed transcriptome analysis of the ADSCs using RNA sequencing. Results The biological activities of O-ADSCs were decreased, including cell immunophenotypic profiles, cell proliferation, and differentiation potential. Furthermore, compared to L-ADSCs, O-ADSCs promoted M1-type macrophage polarization and inhibited M2-type macrophage polarization. Additionally, the mitochondrial morphology of O-ADSCs was altered, with the size of the cells becoming smaller and mitochondrial fragments increasing. O-ADSCs also exhibited decreased mitochondrial membrane potential and membrane fluidity, antioxidative ability, and energy metabolism. With respect to lysosomes, O-ADSCs contained ungraded materials in their lysosomes, enhanced lysosomal permeability, and reduced autophagy and phagocytosis ability. RNA sequence analysis indicated that the signalling pathways related to cell senescence, cancer, and inflammation were upregulated, whereas the signalling pathways associated with stemness, cell differentiation, metabolism, and response to stress and stimuli were downregulated. Conclusions This study indicates that ADSCs from individuals (BMI > 30 kg/m2) exhibit impaired mitochondrial and lysosomal function with decreased biological activity.

Abstract Background Airway remodeling due to increased airway smooth muscle cell (ASMC) mass, likely due to enhanced proliferation, hypertrophy, and migration, has been proven to be highly correlated with decreased lung function in asthma patients. Vascular endothelial growth factor (VEGF) mediates vascular and extravascular remodeling and inflammation and has been proven to be involved in the progression of asthma. Previous studies have focused on the effects of VEGF on ASMC proliferation, but few researchers have focused on the effects of VEGF on human ASMC migration. The purpose of this study was to explore the effect of VEGF on the migration of ASMCs and its related signaling pathway mechanism to provide evidence for the treatment of airway remodeling. Methods We examined the effects of VEGF induction on ASMC migration and explored the mechanisms involved in ASMC migration. Results We found by wound healing and Transwell assays that VEGF promoted ASMC migration. Through the Cell Counting Kit-8 (CCK-8) experiment, we found that VEGF had no significant effect on the proliferation of ASMCs, which excluded the involvement of cell proliferation in the process of wound healing. Moreover, a cellular immunofluorescence assay showed that VEGF promoted F-actin reorganization, and Western blotting showed that VEGF improved RhoA activation and myosin phosphatase targeting subunit-1 (MYPT1) and myosin light chain (MLC) phosphorylation in ASMCs. Treatment with the ROCK inhibitor Y27632 significantly attenuated the effects of VEGF on MYPT1/MLC activation and cell migration. Conclusion In conclusion, the results suggest that the promigratory function of VEGF activates the RhoA/ROCK pathway, induces F-actin reorganization, improves the migration of ASMCs, and provides a better rationale for targeting the RhoA/ROCK pathway for therapeutic approaches in airway remodeling.

Abstract Background Congenital antithrombin deficiency is an autosomal dominant disease that results in deep venous thrombosis and pulmonary embolism, which is mainly caused by mutations in the antithrombin gene (SERPINC1). Since SERPINC1 is highly susceptible to alterations, severe structural and functional changes that promote thrombosis may occur. Clinical presentations vary from different alterations. We report a pregnant case with novel mutation in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms. Case presentation We report a case of a 36-year-old pregnant patient who was diagnosed with congenital antithrombin deficiency for carrying a novel heterozygous mutation, NM_000488:exon5:c.T9 38 C:p. M313T in SERPINC1 presenting transient antithrombin deficiency and multiple venous thromboembolisms. Thrombolytic with alteplase and anticoagulant therapies with low-molecular-weight heparin and warfarin were administrated. After confirming the genetic analysis and the termination of pregnancy, rivaroxaban was administrated, and the thrombosis reduced. Conclusions Our study enriched the mutation database of SERPINC1 gene, provided some new theoretical basis for gene diagnosis and genetic counseling of patients with transient antithrombin deficiency. While it still needs for subsequent exploration of molecular pathogenesis.

IntroductionThe increasing resistance of R. anatipestifer has posed a significant threat to the poultry industry in recent years. The tet gene is the primary determinant of tetracycline resistance in numerous bacteria, and the enzyme modification gene tet(X) is predominantly detected in tetracycline-resistant R. anatipestifer strains.MethodsIn this study, we evaluated the susceptibility of both the standard strain and clinical isolates of R. anatipestifer to doxycycline. And the expression levels of tet(X), tet(A), and tet(O) genes were detected. To assess drug susceptibility, shuttle plasmids were constructed to transfer the tet(X) gene into the standard strain of R. anatipestifer followed by treatment with chlorogenic acid.Results and discussionThe results revealed that the minimum inhibitory concentration of doxycycline for the standard strain was 0.25μg/mL, whereas it exceeded 8μg/mL for the clinical isolates. Furthermore, there was a significant upregulation observed in expression levels of tet(X), tet(A), and tet(O) genes among induced strains. Interestingly, when transferring the tet(X) gene into the standard strain, its sensitivity to doxycycline decreased; however, MIC values for chlorogenic acid remained consistent between both standard and drug-resistant strains of R. anatipestifer. Moreover, we made a surprising discovery that screening passage with chlorogenic acid resulted in increased sensitivity of R. anatipestifer to doxycycline. Further analysis demonstrated a reversal in expression trends among three differentially expressed genes within induced drug resistance group after intervention with chlorogenic acid. The main objective behind this study is to investigate both killing effect exerted by chlorogenic acid on drug-resistant R. anatipestifer as well as its regulatory impact on drug resistance genes. This will provide novel insights and theoretical basis towards development of chlorogenic acid as a promising drug for treatment and control of drug resistance in R. anatipestifer.

In trauma first aid, rapid hemostasis is a priority, extricating patients from hemorrhagic shock and infection risks. This paper explores novel hemostatic materials, using ion-crosslinking and freeze-drying techniques. Iterative experiments determined optimal conditions for the temperature-variable mixing-freeze-drying chemical reaction of sodium alginate (SA)/silk fibroin (SF). We used SA, SA/SF, SA/SF-TB and commercial hemostatic sponge control samples to perform hemostasis experiments on rat liver injury and femoral artery injury models, and to perform wound healing experiments on rat back full-layer skin. The results showed that the hemostatic time and blood loss of SA/SF-TB group rats (liver hemorrhage model: 397.17 ± 34.80 mg, 77.83 ± 7.41 s; Femoral artery bleeding model: 940.33 ± 41.93 mg, 96.83 ± 4.07 s) was significantly better than other experimental groups, and similar to the commercial group. The wound healing experiment showed that the new granulation tissue thickness of SA/SF-TB group was thicker (380.39 ± 28.56 μm) at day 14. In addition, the material properties and biocompatibility of sponges were characterized by cell experiments and in vivo embedding experiments. All the results showed that the SA/SF-TB hemostatic sponge prepared in this study could not only seal the wound quickly and stop bleeding, but also promote the growth of epidermal cells and fibroblasts and accelerate wound healing. This new material solves the shortcomings of traditional materials such as low stability, limited shelf life, high unit price, and has good biocompatibility, easy preparation, rapid hemostasis and other excellent properties. Therefore, this innovative hemostatic material has great prospects and potential in clinical applications.

Abstract Background Despite evidence that severe and poorly controlled asthma are associated with more clinical unmet needs and intensive utilization of healthcare resources, limited data is available on severe asthma expenditure in China. The study aimed to assess Medical Resource Utilization (MRU) costs of asthma and explore the cost drivers in order to better understand the economic burden of the Chinese population suffered from asthma. Methods A retrospective analysis was conducted using Chinese sampled national claim database. Patients aged 6 years and above with primary diagnosis of asthma and asthma-related medical visit/hospitalization during 2015 were included. Medication was used as a proxy per the GINA and China guideline to identify asthma severity (i.e. mild, moderate, and severe). multiple linear regression model was conducted to identify MRU costs drivers. Results 7,254 patients diagnosed with asthma were included: 4,529 (62.4%), 2,200 (30.3%), and 525 (7.2%) had mild, moderate, and severe asthma, respectively. On average, each severe patient spent 6,782 Chinese Yuan (CNY) on asthma treatment and had 57.0% hospitalization rate during the year, 3.9- and 4.4-fold of the average of overall population (P

Tripterygium glycosides tablet (TGT), the classical commercial drug of Tripterygium wilfordii Hook. F. has been effectively used in the treatment of rheumatoid arthritis, nephrotic syndrome, leprosy, Behcet's syndrome, leprosy reaction and autoimmune hepatitis. However, due to its narrow and limited treatment window, TGT-induced organ toxicity (among which liver injury accounts for about 40% of clinical reports) has gained increasing attention. The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing (scRNA-seq) technology. The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin. Using the mouse model, we identified 15 specific subtypes of cells in the liver tissue, including endothelial cells, hepatocytes, cholangiocytes, and hepatic stellate cells. Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations; led to marked inflammatory response, apoptosis and fatty acid metabolism dysfunction in hepatocytes; activated hepatic stellate cells; brought about the activation, inflammation, and phagocytosis of liver capsular macrophages cells; resulted in immune dysfunction of liver lymphocytes; disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways. Thus, these findings elaborate the mechanism underlying TGT-induced acute liver injury, provide new insights into the safe and rational applications in the clinic, and complement the identification of new biomarkers and therapeutic targets for liver protection.

Multimodal public transport network (MPTN) plays an important role in relieving road traffic pressure for metropolitan area. Nevertheless, the impact of an accident happened in an individual station may not only disrupt the station itself or the single lines that go through the station but also spread over the whole network. Therefore, identifying the vulnerable stations is essential for improving the MPTN management against the systematic risk caused by accidents. In this paper, we proposed a route diversity-based approach to measure the vulnerability of stations in MPTN based on the complex network theory. The route constraint parameters were established to reflect the travel time restriction in constructing the set of passengers’ acceptable routes. In addition, an algorithm was formulated to rapidly calculate the route diversity index and meanwhile avoid the “overlapping routes” problem. A simple virtual network was used as a numerical example to compare the proposed approach with the vulnerability evaluation approaches based on degree centrality and betweenness centrality. Finally, the proposed approach was applied to the MPTN of Beijing to explain its effectiveness and potential applications. The results show that the proposed method can efficaciously estimate vulnerable nodes compared with degree centrality and betweenness centrality. Meanwhile, the acceptable routes between any OD pairs in the MPTN are 1–10 according to the constrained parameter. In addition, the average number of acceptable routes between OD pairs of Beijing MPTN is 3.649. By ranking the stations according to their vulnerability, it can be found that the top 5 vulnerable stations are all external traffic hubs or the stations around famous commercial areas. The results suggest that these stations are significant for external transport as well as crucial for internal urban transportation systems. The research output could contribute to the MPTN management in accident prevention and emergency handling.

IntroductionCulicoides plays a crucial role as an insect vector in the field of veterinary medicine. The transmission of significant viruses such as bluetongue virus (BTV) and African horse sickness virus (AHSV) by this insect poses a substantial threat, leading to the development of severe diseases in domestic animals. This study aimed to explore the Culicoides species, identify their blood-meal sources, and assess the presence of BTV and AHSV carried by Culicoides in Yuanyang County, Yunnan Province. The aim was to gain insights into the potential vectors of these two viruses and elucidate their potential roles in the transmission of pathogens.MethodsThe midges were collected from cattle (Bos indicus), pig (Sus scrofa), and goat (Capra hircus) pens in Yuanyang County, Yunnan Province in June 2020. Initial identification of midges was conducted through morphological characteristics, followed by molecular identification using the cytochrome C oxidase subunit I (COI) gene. The determination of Culicoides blood-meal sources was accomplished using specific primers targeting the cytochrome b (Cyt b) gene from potential hosts. BTV and AHSV RNA were identified in Culicoides pools through the application of reverse transcriptase PCR and quantitative real-time PCR. Nucleotide homology and phylogenetic analysis were performed using MegAlign (DNAStar) and Mega 6.0 software.ResultsA total of 6,300 Culicoides, consisting of C. oxystoma, C. arakawai, C. imicola, and C. innoxius, were collected from cattle, pigs, and goat pens. The engorgement rates for these species were 30.2%, 54.6%, 75%, and 66.7%, respectively. In the cattle pen, the prevailing species is C. oxystoma (100%). In the pig pen, C. arakawai dominates (70%), with C. oxystoma following at 30%. In the goat pen, C. imicola holds the majority (45.45%), trailed by C. oxystoma (25%), C. innoxius (20.45%), and C. arakawai (9.09%). These Culicoides species were identified as feeding on cattle, pigs, goats, chickens (Gallus gallus), and humans (Homo sapiens). The positivity rates for BTV were 20.00% and 11.54% in blood-fed specimens of C. imicola and C. oxystoma, respectively. Conversely, the positivity rates for BTV in non-blood-fed specimens were 0.00% and 6.67% for C. imicola and C. oxystoma, respectively. BTV was not detected in C. arakawai and C. innoxius. The specimens (YY86) from C. imicola that tested positive for BTV had the closest genetic relationship to YTS-4 isolated from Mangshi, Yunnan Province in 1996. All test results for the nucleic acid of AHSV were negative.ConclusionThe study reveals variations in the species distribution, community composition, blood sucking rate, and blood-feeding sources of Culicoides across different habitats. Notably, C. imicola and C. oxystoma emerge as potential vectors for the transmission of BTV in local animals. Accordingly, this investigation provides crucial insights that can serve as a valuable reference for the prevention and control of BTV in local animals, particularly from the perspective of vector management.

Abstract Background Epicardial adipose tissue (EAT) has been suggested to exert deleterious effects on myocardium and cardiovascular disease (CVD) consequence. We evaluated the associations of EAT thickness with adverse outcomes and its potential mediators in the community. Methods Participants without heart failure (HF) who had undergone cardiac magnetic resonance (CMR) to measure EAT thickness over the right ventricular free wall from the Framingham Heart Study were included. The correlation of EAT thickness with 85 circulating biomarkers and cardiometric parameters was assessed in linear regression models. The occurrence of HF, atrial fibrillation, coronary heart disease (CHD), and other adverse events was tracked since CMR was implemented. Their associations with EAT thickness and the mediators were evaluated using Cox regression and causal mediation analysis. Results Of 1554 participants, 53.0% were females. Mean age, body mass index, and EAT thickness were 63.3 years, 28.1 kg/m2, and 9.8 mm, respectively. After fully adjusting, EAT thickness positively correlated with CRP, LEP, GDF15, MMP8, MMP9, ORM1, ANGPTL3, and SERPINE1 and negatively correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP), IGFBP1, IGFBP2, AGER, CNTN1, and MCAM. Increasing EAT thickness was associated with smaller left ventricular end-diastolic dimension, thicker left ventricular wall thickness, and worse global longitudinal strain (GLS). During a median follow-up of 12.7 years, 101 incident HF occurred. Per 1-standard deviation increment of EAT thickness was associated with a higher risk of HF (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.19–1.72, P

The phytochrome-interacting factor (PIF) proteins are part of a subfamily of basic helix–loop–helix (bHLH) transcription factors that integrate with phytochromes (PHYs) and are known to play important roles in adaptive changes in plant architecture. However, the characterization and function of PIFs in potatoes are currently poorly understood. In this study, we identified seven PIF members in potatoes and named them StPIF01-1, StPIF01-2, StPIF03, StPIF06-1, StPIF06-2, StPIF07, and StPIF09 based on their location in potato chromosomes. The chromosomal location, gene structures, physicochemical characteristics, phylogenetic tree, and tissue-specific expression of StPIFs were also analyzed. RT-qPCR analysis revealed that the StPIF3 gene was highly induced by shade and may play a crucial regulatory role in potato responses to shade stress. Also, multiple cis-regulatory elements involved in light response were detected in the promoter of the StPIF genes. Subcellular localization analysis indicated that the StPIF3-encoding protein is mainly localized in the nucleus. Transgenic overexpression of StPIF3 in potatoes increased stem length, chlorophyll accumulation, and enhanced shade-avoidance symptoms, whereas the StPIF3-interfering lines had a lower plant height and more chlorophyll accumulation. These findings enhance our comprehension of StPIF gene roles, potentially advancing potato yield and quality research. This study provides detailed information about StPIFs and identifies the function of StPIF3, which is involved in shade-avoidance syndrome.

IntroductionBanna virus (BAV), a potential pathogen that may cause human encephalitis, is the prototype species of genus Seadornaviru within the family Reoviridae, and has been isolated from a variety of blood-sucking insects and mammals in Asia.MethodsCulicoides, Mosquitoes, and Ticks were collected overnight in Yunnan, China, during 2016-2023 using light traps. Virus was isolated from these collected blood-sucking insects and grown using Aedes albopictus (C6/36) cells. Preliminary identification of the virus was performed by agarose gel electrophoresis (AGE). The full genome sequences of the BAVs were determined by full-length amplification of cDNAs (FLAC) and sequenced using next-generation sequencing.ResultsIn this study, 13 strains BAV were isolated from Culicoides, Mosquitoes and Ticks. Their viral genome consisted of 12 segments of double-stranded RNA (dsRNA), and with three distinct distribution patterns. Sequence analysis showed that Seg-5 of four strains (SJ_M46, SJ_M49, JC_M19-13 and JC_C24-13) has 435 bases nucleotide sequence insertions in their ORF compared to other BAVs, resulting in the length of Seg-5 up to 2128 nt. There are 34 bases sequence deletion in Seg-9 of 3 strains (WS_T06, MS_M166 and MS_M140). Comparison of the coding sequences of VP1, VP2, VP5, VP9 and VP12 of the 13 BAV strains, the results show that VP1, VP2 and VP12 are characterised by high levels of sequence conservation, while VP9 is highly variable, under great pressure to adapt and may be correlated with serotype. While also variable, VP5 appears to be under less adaptive pressure than VP9. Additionally, phylogenetic analysis indicates that the 13 BAV strains locate in the same evolutionary cluster as BAVs isolated from various blood-sucking insects, and are clustered according to geographical distribution.ConclusionThe data obtained herein would be beneficial for the surveillance of evolutionary characteristics of BAV in China and neighboring countries as well as extend the knowledge about its genomic diversity and geographic distribution.

Summary: DEAH-Box Helicase 38 (DHX38) is a pre-mRNA splicing factor and also a disease-causing gene of autosomal recessive retinitis pigmentosa (arRP). The role of DHX38 in the development and maintenance of the retina remains largely unknown. In this study, by using the dhx38 knockout zebrafish model, we demonstrated that Dhx38 deficiency causes severe differentiation defects and apoptosis of retinal progenitor cells (RPCs) through disrupted mitosis and increased DNA damage. Furthermore, we found a significant accumulation of R-loops in the dhx38-deficient RPCs and human cell lines. Finally, we found that DNA replication stress is the prerequisite for R-loop-induced DNA damage in the DHX38 knockdown cells. Taken together, our study demonstrates a necessary role of DHX38 in the development of retina and reveals a DHX38/R-loop/replication stress/DNA damage regulatory axis that is relatively independent of the known functions of DHX38 in mitosis control.

Background and Objectives: While there exists a significant wastage of platelets on one side (volatile demands and short lifetime), there is also a shortage for use on the other (lack of donors and emergency transfusions). A new centralized management system was established to tackle this dilemma. Methods: To assess the function of this system, data were collected from the Fengxian Blood Bank (FBB) Collection and Supply Information System during 2016 and 2018, then analyzed by IBM SPSS Statistics version 20. Results: Since implementing the centralized management system, a total of 1340 units of apheresis platelets were distributed by FBB. However, the number of units collected was 2737, twice as much as what had been distributed. With the aid of the system, the excess of 1644 units of apheresis platelets were transferred to the Shanghai Blood Center (SBC) inventory at their disposal. On the other hand, 247 units (included in 1340 distributed units) were compensated by SBC during the platelet shortage. In addition, the hospital demand meeting rate shows a significant increase from 82.61% to 99.78%, especially for type AB which increases from 62% to 100%. Conclusions: In conclusion, the centralized management system vastly improved the efficiency of platelet collection and distribution by the regional supply and demand. Such success would be a superb example of blood banks facing similar problems.

Abstract Background In recent years, with the development of monitoring conditions and the application of pulmonary vascular-targeted drugs, pregnancy outcomes in women with pulmonary hypertension (PH) have improved, but the maternal mortality rate is still high. The purpose of this study was to describe the maternal-foetal outcomes in pregnant women with PH. Methods The clinical data of 154 pregnant women with PH who were admitted to the Third Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2020 were collected and descriptively analysed. Results Among the 154 pregnant women with PH, 6 (3.9%) had idiopathic pulmonary arterial hypertension (iPAH), 41 (26.6%) had pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH), 45 (29.2%) had PAH related to other diseases (oPAH), and 62 (40.3%) had PH related to left heart disease (LHD-PH). The systolic pulmonary artery pressure (sPAP) was 36–49 mmHg in 53.2% of the patients, 50–69 mmHg in 22.1% of the patients and ≥ 70 mmHg in 24.7% of the patients. Five (3.2%) pregnant women died within 1 week after delivery; iPAH patients had the highest mortality rate (3/6, 50%). Fifty-four patients (35.1%) were admitted to the intensive care unit (ICU), and the incidence of heart failure during pregnancy was 14.9%. A total of 70.1% of the patients underwent caesarean section; 42.9% had premature infants; 28.6% had low-birth-weight (LBW) infants; 13.0% had very-low-birth-weight (VLBW) infants; 3.2% had extremely-low-birth-weight (ELBW) infants; 61% had small for gestational age (SGA) infants; and 1.9% experienced neonatal mortality. Conclusion There were significant differences in the maternal-foetal outcomes in the iPAH, CHD-PAH, oPAH and LHD-PH groups. Maternal mortality was highest in the iPAH group; therefore, iPAH patients should be advised to prevent pregnancy. Standardized and multidiscipline-assisted maternal management is the key to improving maternal-foetal outcomes.

Abstract Mutations in TUB-like protein 1 (TULP1) are associated with severe early-onset retinal degeneration in humans. However, the pathogenesis remains largely unknown. There are two homologous genes of TULP1 in zebrafish, namely tulp1a and tulp1b. Here, we generated the single knockout (tulp1a −/− and tulp1b −/− ) and double knockout (tulp1-dKO) models in zebrafish. Knockout of tulp1a resulted in the mislocalization of UV cone opsins and the degeneration of UV cones specifically, while knockout of tulp1b resulted in mislocalization of rod opsins and rod-cone degeneration. In the tulp1-dKO zebrafish, mislocalization of opsins was present in all types of photoreceptors, and severe degeneration was observed at a very early age, mimicking the clinical manifestations of TULP1 patients. Photoreceptor cilium length was significantly reduced in the tulp1-dKO retinas. RNA-seq analysis showed that the expression of tektin2 (tekt2), a ciliary and flagellar microtubule structural component, was downregulated in the tulp1-dKO zebrafish. Dual-luciferase reporter assay suggested that Tulp1a and Tulp1b transcriptionally activate the promoter of tekt2. In addition, ferroptosis might be activated in the tulp1-dKO zebrafish, as suggested by the up-regulation of genes related to the ferroptosis pathway, the shrinkage of mitochondria, reduction or disappearance of mitochondria cristae, and the iron and lipid droplet deposition in the retina of tulp1-dKO zebrafish. In conclusion, our study establishes an appropriate zebrafish model for TULP1-associated retinal degeneration and proposes that loss of TULP1 causes defects in cilia structure and opsin trafficking through the downregulation of tekt2, which further increases the death of photoreceptors via ferroptosis. These findings offer insight into the pathogenesis and clinical treatment of early-onset retinal degeneration.

Objective To analyze the difference of circulating threshold (Ct) of polymerase chain reaction (PCR) in blood station laboratories during the external quality assessment, and to put forward suggestions for the quality improvement of participating laboratories. Methods From 2018 to 2021, the blood station laboratories participated in the external laboratory quality assessment of CITIC including blood screening items with nucleic acid testing method. The data of Roche diagnostic reagent group were used as the source, and the detected Ct values of three groups of quality control samples of HBV A subtype (400 IU/mL), HCV 1b subtype (400 IU/mL) and HIV B genotype (500 IU/mL) were used as the objects. The data were grouped according to quality control (sample) batches, reagent batches and different laboratories. Using the statistical method of variance analysis (assuming P

Biting midges are one of the most common hematophagous insects. They are capable of transmitting a wide range of arboviruses and have a significant impact on public health and veterinary medicine. Herein, from midge samples collected in 2013 in Yunnan, China, one sample induced a cell cytopathic effect (CPE) in BHK-21, MA104, and PK15 cell lines. Next-generation sequencing data, RACE and PCR determined the genome sequence of the sample and designated as an Oya virus (OYAV) isolate SZC50. Phylogenetic analysis of the sample revealed that it was cluster into viruses from species Orthobunyavirus catqueense. The open reading frames of S, M, and L segment of OYAV SZC50 were closest to those of OYAV SC0806. Moreover, 831 serum samples (736 pigs, 45 cattle, and 50 sheep) were gathered from 13 cities in Yunnan Province to detect neutralizing antibody of OYAV SZC50. A significant proportion of OYAV SZC50 antibody (more than 30%) was found in Yunnan pig populations, with the positive rate of OYAV SZC50 antibody in pigs from Malipo reaching 95%. To determine the pathogenicity of OYAV SZC50, we chose three animal models: specific pathogen-free Kunming mice, C57BL/6 mice lacking the interferon α/β receptor, and chicken embryos. At 5, 6, and 7 days post-infection, all adult and suckling C57BL/6 mice, and specific pathogen-free suckling Kunming mice were dead. Our finding was expanding the knowledge about the infection and pathogenic risk of the neglected virus in the Orthobunyavirus.

Introduction: Pathogenic mutations in RPGRORF15, one of two major human RPGR isoforms, were responsible for most X-linked retinitis pigmentosa cases. Previous studies have shown that RPGR plays a critical role in ciliary protein transport. However, the precise mechanisms of disease triggered by RPGRORF15 mutations have yet to be clearly defined. There are two homologous genes in zebrafish, rpgra and rpgrb. Zebrafish rpgra has a single transcript homologous to human RPGRORF15; rpgrb has two major transcripts: rpgrbex1-17 and rpgrbORF15, similar to human RPGRex1-19 and RPGRORF15, respectively. rpgrb knockdown in zebrafish resulted in both abnormal development and increased cell death in the dysplastic retina. However, the impact of knocking down rpgra in zebrafish remains undetermined. Here, we constructed a rpgra mutant zebrafish model to investigate the retina defect and related molecular mechanism.Methods: we utilized transcription activator-like effector nuclease (TALEN) to generate a rpgra mutant zebrafish. Western blot was used to determine protein expression. RT-PCR was used to quantify gene transcription levels. The visual function of embryonic zebrafish was detected by electroretinography. Immunohistochemistry was used to observe the pathological changes in the retina of mutant zebrafish and transmission electron microscope was employed to view subcellular structure of photoreceptor cells.Results: A homozygous rpgra mutant zebrafish with c.1675_1678delins21 mutation was successfully constructed. Despite the normal morphological development of the retina at 5 days post-fertilization, visual dysfunction was observed in the mutant zebrafish. Further histological and immunofluorescence assays indicated that rpgra mutant zebrafish retina photoreceptors progressively began to degenerate at 3-6 months. Additionally, the mislocalization of cone outer segment proteins (Opn1lw and Gnb3) and the accumulation of vacuole-like structures around the connecting cilium below the OSs were observed in mutant zebrafish. Furthermore, Rab8a, a key regulator of opsin-carrier vesicle trafficking, exhibited decreased expression and evident mislocalization in mutant zebrafish.Discussion: This study generated a novel rpgra mutant zebrafish model, which showed retinal degeneration. our data suggested Rpgra is necessary for the ciliary transport of cone-associated proteins, and further investigation is required to determine its function in rods. The rpgra mutant zebrafish constructed in this study may help us gain a better understanding of the molecular mechanism of retinal degeneration caused by RPGRORF15 mutation and find some useful treatment in the future.

Iodoacetic acid (IAA) is an emerging and the most genotoxic iodinated disinfection byproduct to date. IAA can disrupt the thyroid endocrine function in vivo and in vitro, but the underlying mechanisms remain unclear. In this work, transcriptome sequencing was used to investigate the effect of IAA on the cellular pathways of human thyroid follicular epithelial cell line Nthy-ori 3–1 and determine the mechanism of IAA on the synthesis and secretion of thyroid hormone (TH) in Nthy-ori 3–1 cells. Results of transcriptome sequencing indicated that IAA affected the TH synthesis pathway in Nthy-ori 3–1 cells. IAA reduced the mRNA expression of thyroid stimulating hormone receptor, sodium iodide symporter, thyroid peroxidase, thyroglobulin, paired box 8 and thyroid transcription factor-2, inhibited the cAMP/PKA pathway and Na+-K+-ATPase, and decreased the iodine intake. The results were confirmed by our previous findings in vivo. Additionally, IAA downregulated glutathione and the mRNA expression of glutathione peroxidase 1, leading to increased reactive oxygen species production. This study is the first to elucidate the mechanisms of IAA on TH synthesis in vitro. The mechanisms are associated with down-regulating the expression of genes related to TH synthesis, inhibiting iodine uptake, and inducing oxidative stress. These findings may improve future health risk assessment of IAA on thyroid in human.

Two strains of viruses, JC13C644 and JC13C673, were isolated from Culicoides tainanus collected in Jiangcheng County, Yunnan Province, situated along the border area shared by China, Laos, and Vietnam. JC13C644 and JC13C673 viruses can cause cytopathic effect (CPE) in mammalian cells BHK21 and Vero cells, and cause morbidity and mortality in suckling mice 48 h after intracerebral inoculation. Whole-genome sequencing was performed, yielding complete sequences for all 10 segments from Seg-1 (3942nt) to Seg-10 (810nt). Phylogenetic analysis of the sub-core-shell (T2) showed that the JC13C644 and JC13C673 viruses clustered with the Epizootic Hemorrhagic Disease Virus (EHDV) isolated from Japan and Australia, with nucleotide and amino acid homology of 93.1% to 98.3% and 99.2% to 99.6%, respectively, suggesting that they were Eastern group EHDV. The phylogenetic analysis of outer capsid protein (OC1) and outer capsid protein (OC2) showed that the JC13C644 and JC13C673 viruses were clustered with the EHDV-10 isolated from Japan in 1998, with the nucleotide homology of 98.3% and 98.5%, and the amino acid homology of 99.6% and 99.6–99.8%, respectively, indicating that they belong to the EHDV-10. Seroepidemiological survey results demonstrated that JC13C644 virus-neutralizing antibodies were present in 29.02% (177/610) of locally collected cattle serum and 11.32% (89/786) of goat serum, implying the virus’s presence in Jiangcheng, Yunnan Province. This finding suggests that EHDV-10 circulates not only among blood-sucking insects in nature but also infects local domestic animals in China. Notably, this marks the first-ever isolation of the virus in China and its discovery outside of Japan since its initial isolation from Japanese cattle. In light of these results, it is evident that EHDV Serotype 10 exists beyond Japan, notably in the natural vectors of southern Eurasia, with the capacity to infect local cattle and goats. Therefore, it is imperative to intensify the surveillance of EHDV infection in domestic animals, particularly focusing on the detection and monitoring of new virus serotypes that may emerge in the region and pose risks to animal health.

ObjectiveTraining contributes to the effectiveness of aerosol inhalation therapy. However, qualitative and quantitative evaluation of effective training methods is rarely reported. This study aimed to evaluate the effectiveness of a standardized training model by pharmacists based on verbal instruction and physical demonstration in improving patients' ability to use inhalers using qualitative and quantitative methods. Risk or protective factors affecting correct inhaler use were also explored.Methods431 Outpatients with asthma or COPD were recruited and randomly divided into a standardized training group (n = 280) and a usual training group (control group, n = 151). A framework of qualitative (e.g., multi-criteria analysis) and quantitative comparisons [percentage of correct use (CU%), percentage of complete error (CE%), and percentage of partial error (PE%)] was established to evaluate the two training models. In addition, the changes of key factors (age, education level, adherence, device type, etc.) influencing patients' ability to use inhalers of two models were observed.ResultsThe multi-criteria analysis showed that the standardized training model had comprehensive advantages in qualitative indicators. The average correct use percentage (CU%) of the standardized training group was significantly higher than that of the usual training group (77.6% vs. 35.5%). A stratified analysis further demonstrated that the ORs (95%CI) in the usual training group of age and educational level was 2.263 (1.165–4.398) and 0.556 (0.379–0.815), while in the standardized training group, age and educational level were not the key factors influencing the ability to use inhaler devices (P > 0.05). Logistic regression analysis demonstrated that standardized training was a protective factor for inhalation ability.ConclusionThese findings indicate that the framework of qualitative and quantitative comparisons could be used to evaluate training models, and the standardized training model by pharmacists can significantly improve patients' ability to use inhalers correctly and address the influence of older age and lower education because of its methodological advantages. Further studies with more extended follow-up are needed to validate the role of the standardized training model by pharmacists in the correct use of inhalers.Clinical trial registrationchictr.org.cn, ChiCTR2100043592 (23-02-2021).

Abstract Photoplethysmography (PPG) signal is a novel biometric trait related to the identity of people; many time‐ and frequency‐domain methods for PPG biometric recognition have been proposed. However, the existing domain methods for PPG biometric recognition only consider a single domain or the feature‐level fusion of time and frequency domains, without considering the exploration of the fusion correlations of the time and frequency domains. The authors propose a time–frequency fusion for a PPG biometric recognition method with collective matrix factorisation (TFCMF) that leverages collective matrix factorisation to learn a shared latent semantic space by exploring the fusion correlations of the time and frequency domains. In addition, the authors utilise the ℓ2,1 norm to constrain the reconstruction error and shared matrix, which can alleviate the influence of noise and intra‐class variation, and ensure the robustness of learnt semantic space. Experiments demonstrate that TFCMF has better recognition performance than current state‐of‐the‐art methods for PPG biometric recognition.

MicroRNAs are a class of endogenous, non-coding, small-RNA molecules with important functions in plant development and stress response processes. Root systems are important because they allow plants to absorb nutrients and water from the soil and are fundamental for anchoring the plant and responding to environmental signals. However, the roles of miRNAs underlying root development remain poorly investigated in potato. In this research, small-RNA sequencing was performed to thoroughly detect underlying miRNAs and their roles in regulating root development between the early root (ER) stage and the mature root (MR) stage of potato roots. A total of 203 known and 137 novel miRNAs were obtained, and 64 differentially expressed miRNAs (DEMs) were identified between the ER and MR stages. The expression patterns of 12 DEMs were also determined via qRT-PCR. In addition, a mixed degradome library was constructed from the ER and the MR stages to identify the targets of the identified miRNAs, and 2400 target genes were verified to be the targets of 131 miRNAs. Based on target annotation, we identified that nine target genes of six DEMs were probably involved in potato root development, and eight targets of six DEMs were validated via 5’-RLM-RACE assays. These targets may participate in root development by regulating cell proliferation, root cultures (PGSC0003DMT400013837), root meristem growth (PGSC0003DMT400079970), root morphogenesis (PGSC0003DMT400040282), post-embryonic root development (PGSC0003DMT400021612), root hair elongation (PGSC0003DMT400034518), cell wall repair (PGSC0003DMT400074930), and auxin polar transport (PGSC0003DMT400079970), and by negatively regulating cell proliferation (PGSC0003DMT400009997) and cell growth (PGSC0003DMT400003464). The qRT-PCR analysis indicated that most miRNAs have opposing expression patterns to their targets. It is widely accepted that potato root development is regulated by miRNAs, among which stu-miR8006-p5-1ss9AT is substantially down-regulated during root development. We show here that the suppression of stu-miR8006-p5-1ss9AT led to an alteration in the potato root architecture and that it targeted auxin induction in the root culture protein 12-encoding gene that is potentially involved in the regulation of root development. In addition, the suppression of stu-miR8006-p5-1ss9AT led to a significant alteration in the potato root architecture. Altogether, our results might provide some useful insights into stu-miR8006-p5-1ss9AT and the crucial role that it plays in potato root development; they could also facilitate the molecular genetic breeding of potato.

Semantic segmentation of high spatial resolution (HSR) remote sensing images (RSIs) plays an important role in many applications. However, HSR RSIs have significantly larger spatial sizes than typical natural images, which results in fewer valuable samples when training models. In addition, fusing multiscale features is the key step in obtaining features with strong semantic and high spatial information. However, current feature fusion methods are too straightforward to address misalignment issues. To handle these two problems, we propose an annealing augmented and aligned segmentation network, named $\text{A}^{3}$Seg. Specifically, we propose an annealing online hard example mining (AOHEM) strategy to automatically select more valuable samples during the training stage. Based on AOHEM, a contextual augmentation block is proposed to extract sufficient contextual information using three different attention mechanisms in consideration of three different feature properties. Finally, we propose a novel feature alignment block to fuse features at different levels by alignment with the guidance of a salient feature. Experimental results on three different HSR RSIs datasets demonstrate that the proposed method outperforms the state-of-the-art general semantic segmentation methods with a better tradeoff between accuracy and complexity.

IntroductionThe amygdala plays an important role in stress responses and stress-related psychiatric disorders. It is possible that amygdala connectivity may be a neurobiological vulnerability marker for stress responses or stress-related psychiatric disorders and will be useful to precisely identify the vulnerable individuals before stress happens. However, little is known about the relationship between amygdala connectivity and subsequent stress responses. The current study investigated whether amygdala connectivity measured before experiencing stress is a predisposing neural feature of subsequent stress responses while individuals face an emergent and unexpected event like the COVID-19 outbreak.MethodsData collected before the COVID-19 pandemic from an established fMRI cohort who lived in the pandemic center in China (Hubei) during the COVID-19 outbreak were used to investigate the relationship between amygdala connectivity and stress responses during and after the pandemic in 2020. The amygdala connectivity was measured with resting-state functional connectivity (rsFC) and effective connectivity.ResultsWe found the rsFC of the right amygdala with the dorsomedial prefrontal cortex (dmPFC) was negatively correlated with the stress responses at the first survey during the COVID-19 outbreak, and the rsFC between the right amygdala and bilateral superior frontal gyri (partially overlapped with the dmPFC) was correlated with SBSC at the second survey. Dynamic causal modeling suggested that the self-connection of the right amygdala was negatively correlated with stress responses during the pandemic.DiscussionOur findings expand our understanding about the role of amygdala in stress responses and stress-related psychiatric disorders and suggest that amygdala connectivity is a predisposing neural feature of subsequent stress responses.

BackgroundDespite the demonstrated association between empathy and gambling at the behavioral level, limited neuroimaging research on empathy and gambling disorder (GD) has been conducted. Whether and how the brain network of empathy and that of gambling interact in disordered gamblers has not been investigated. This study aimed to address this research gap by examining the hierarchical organizational patterns, in which the differences of causal interactions of these networks between disordered gamblers and healthy controls were revealed.MethodsResting-state functional magnetic resonance imaging (fMRI) data of 32 disordered gamblers and 56 healthy controls were included in the formal analysis. Dynamic causal modeling was used to examine the effective connectivity within and between empathy and gambling networks among all participants.ResultsAll participants showed significant effective connectivity within and between empathy and gambling networks. However, compared with healthy controls, disordered gamblers displayed more excitatory effective connectivity within the gambling network, the tendency to display more excitatory effective connectivity from the empathy network to the gambling network, and reduced inhibitory effective connectivity from the gambling network to the empathy network.ConclusionThe exploratory study was the first to examine the effective connectivity within and between empathy and gambling networks among disordered gamblers and healthy controls. These results provided insights into the causal relationship between empathy and gambling from the neuroscientific perspective and further confirmed that disordered gamblers show altered effective connectivity within and between these two brain networks, which may be considered to be a potential neural index for GD identification. In addition, the altered interactions between empathy and gambling networks may also indicate the potential targets for the neuro-stimulation intervention approach (e.g., transcranial magnetic stimulation).

Currently, the issue of marine biodiversity in areas beyond national jurisdiction (ABNJ) has made a lot of significant progress in both international legislative process and national practices. As a State Party to UNCLOS, China has actively participated in the negotiations of the BBNJ agreement, in which the marine protected areas (MPAs) as one of the area-based management tools have been an issue of great concern. It is considered to be a feasible and direct conservation tool. In order to evaluate the possibility of China’s participation in the establishment of MPAs in the future, this paper analyzes the drivers for and limits on China’s involvement in the construction of MPAs in the context of the current Chinese situation. And it also puts forward possible countermeasures on how to deal with the challenges brought by the MPAs in ABNJ to China. It is concluded that there is a great possibility that China will eventually choose to participate in the establishment of MPAs in ABNJ as China advocates the concept of a maritime community with a shared future.

Mammalian transducin-like enhancer of split family proteins (TLEs) are homologous to Drosophila Groucho (Gro) and are essential transcriptional repressors. Seven TLE family members, TLE1-7, have been identified to date. These proteins do not bind DNA directly; instead, they bind a set of transcription factors and thereby inhibit target gene expression. Loss of TLEs in mice usually leads to defective early development; however, TLE functions in developmentally mature cells are unclear. Recent studies have revealed that TLEs are dysregulated in certain human cancer types and may function as oncogenes or tumor suppressors in different contexts. TLE levels also affect the efficacy of cancer treatments and the development of drug resistance. In addition, TLEs play critical roles in the development and function of immune cells, including macrophages and lymphocytes. In this review, we provide updates on the expression, function, and mechanism of TLEs; discuss the roles played by TLEs in tumorigenesis and the inflammatory response; and elaborate on several TLE-associated signaling pathways, including the Notch, Wnt, and MAPK pathways. Finally, we discuss potential strategies for targeting TLEs in cancer therapy.

A comprehensive understanding of the changing patterns and the contribution of each component of the forest ecosystem to evapotranspiration is necessary for an accurate assessment of biological quality, terrestrial ecosystem production, energy exchange, and water use efficiency. In this study, two methods (i.e., the sap-flow and lysimeter methods) were used to partition evapotranspiration (ET) into evaporation(E) and transpiration(T) components using stable isotope techniques. The factors affecting the contribution of T to ET (FT) were evaluated. The results showed that FT presents seasonal variation patterns throughout the year. Both methods accurately simulated the ET partitioning and its seasonal variation. The ET value estimated by the sap-flow method was less than that estimated by the lysimeter method. In contrast, the simulated value of T calculated using the lysimeter method was higher than that calculated by the sap-flow method. However, this was within allowable limits. The lysimeter method is more accurate and suitable for monitoring forest ecosystem evapotranspiration in practical experiments. This study provides a technical reference for the optimal calculation method of ET partitioning using a stable isotope-based technique. It provides baseline information to better understand water vapour exchange in forest ecosystems in China.

In this paper, we mainly propose three preconditioners for solving double saddle point problems, which arise from some practical problems. Firstly, the solvability of this kind of problem is investigated under suitable assumption. Next, we prove that all the eigenvalues of the three preconditioned matrices are 1. Furthermore, we analyze the eigenvector distribution and the upper bound of the minimum polynomial degree of the corresponding preconditioned matrix. Finally, numerical experiments are carried to show the effectiveness of the proposed preconditioners.

Electrocardiogram (ECG) signal is a promising biometric trait, and many methods have been proposed for ECG biometric recognition. However, it is challenging to design a robust and precise method to improve the recognition performance of ECG signals with noise and signal variation. We present a multi-feature sparse representations learning model via collective matrix factorization for ECG biometric recognition, MSRCMF for short. First, we extract one-dimensional local binary pattern (1D-LBP), shape and wavelet features of ECG signals and then obtain their sparse representations. Second, to extract discriminative information and preserve the intra- and inter-subject similarities, we leverage the collective matrix factorization on multiple sparse representations and the label information to obtain the latent semantic space. At last, we can recognize the ECG signals in the learned semantic space. Extensive experiments on four ECG databases show that MSRCMF can achieve competitive performance compared to state-of-the-art methods.

The influencing factors of kite culture inheritance form a complex system that is influenced by many factors, such as the inheritance mode, audience preferences, communication mode and social environment, and the influencing factors are plentiful and nonlinear. In this paper, we use the literature search method and Delphi method to determine the set of influencing factors and clarify the direct binary relationships between each of them. Based on the results of these methods, the Adversarial Interpretive Structure Model (AISM) is modeled and used, and the AISM model with a cause-effect reachable hierarchy is obtained by comparing the directed topological diagram of a pair of up and down diagrams and conducting a comprehensive analysis of the influencing factors of kite culture inheritance. Finally, the validity of the model is proved through the project practice of talent training in the National Art Foundation of China. The results of this study show the following: policies and regulations and product characteristics are the root cause elements affecting the inheritance of intangible cultural heritage.

Chicken anemia virus (CAV), which has been reported in many countries, causes severe anemia and immunosuppression in chickens. In this study, a CAV strain YN04 belonging to genotype A was first identified from infected chickens in Yunnan province, China. Moreover, the animal infection experiments further confirmed that the strain YN04 is a highly pathogenic strain, which can cause 86.67% mortality in chickens in the infection group. The mean death time of infected chickens was 13.1 days post infection (dpi). CAV infection induced severe anemia with significant decrease in packed cell volume (PCV), and serious atrophy and lesion of thymus and bursa with high viral load at 14 dpi. Besides, CAV infection caused a sharp decrease in chicken body weight and immune organ indices including the ratio of thymus or bursa to body weight at 21 dpi, which displayed the potential immunosuppression state at this stage. These findings enrich the epidemiological data on CAV and may provide information for preventing its further spread in Yunnan province, China.

Neural retina leucine zipper (NRL) is an essential gene for the fate determination and differentiation of the precursor cells into rod photoreceptors in mammals. Mutations in NRL are associated with the autosomal recessive enhanced S-cone syndrome and autosomal dominant retinitis pigmentosa. However, the exact role of Nrl in regulating the development and maintenance of photoreceptors in the zebrafish (Danio rerio), a popular animal model used for retinal degeneration and regeneration studies, has not been fully determined. In this study, we generated an nrl knockout zebrafish model via the CRISPR-Cas9 technology and observed a surprising phenotype characterized by a reduced number, but not the total loss, of rods and over-growth of green cones. We discovered two waves of rod genesis, nrl-dependent and -independent at the embryonic and post-embryonic stages, respectively, in zebrafish by monitoring the rod development. Through bulk and single-cell RNA sequencing, we characterized the gene expression profiles of the whole retina and each retinal cell type from the wild type and nrl knockout zebrafish. The over-growth of green cones and mis-expression of green-cone-specific genes in rods in nrl mutants suggested that there are rod/green-cone bipotent precursors, whose fate choice between rod versus green-cone is controlled by nrl. Besides, we identified the mafba gene as a novel regulator of the nrl-independent rod development, based on the cell-type-specific expression patterns and the retinal phenotype of nrl/mafba double-knockout zebrafish. Gene collinearity analysis revealed the evolutionary origin of mafba and suggested that the function of mafba in rod development is specific to modern fishes. Furthermore, the altered photoreceptor composition and abnormal gene expression in nrl mutants caused progressive retinal degeneration and subsequent regeneration. Accordingly, this study revealed a novel function of the mafba gene in rod development and established a working model for the developmental and regulatory mechanisms regarding the rod and green-cone photoreceptors in zebrafish.

Abstract TaB2-SiC coating modified by different content of MoSi2 was fabricated on graphite substrate with SiC inner coating by liquid phase sintering to elevate the anti-oxidation capability of the TaB2-SiC coatings. As compared to the sample with the TaB2—40wt%SiC coating, the coating sample modified with MoSi2 exhibited a weight gain trend at lower temperatures, the fastest weight loss rate went down by 76%, and the relative oxygen permeability value reduced from about 1% to near 0. More importantly, the large amount of SiO2 glass phase produced over the coating during oxidation was in contact with the modification of MoSi2, which was proved to be beneficial to the dispersion of Ta-oxides. A concomitantly formed continuous Ta-Si-O-B compound glass layer showed excellent capacity to prevent oxygen penetration. However, when the TaB2 content was sacrificed to increase the MoSi2 content, the relative oxygen permeability of the coating increased instead of decreased. Thus, on the basis of ample TaB2 content, increasing the MoSi2 content of the coating is conducive to reducing the relative oxygen permeability of the coatings in a broad temperature region.

Resistance to platinum-based chemotherapy becomes a major obstacle in non-small-cell lung cancer (NSCLC) treatment. Overexpression of the excision repair cross-complementing 1 (ERCC1) gene is reported to negatively influence the effectiveness of cisplatin-based therapy for NSCLC cells. In this study, we confirm that high ERCC1 expression correlates with cisplatin resistance in NSCLC cells. Importantly, histone deacetylase inhibitors (HDACis) re-sensitize ERCC1-high NSCLC cells to cisplatin both in vitro and in vivo. Mechanistically, the HDACi induces the expression of miR-149 by acetylation and activation of E2F1, which directly targets ERCC1 and inhibits ERCC1 expression. Inhibition of miR-149 reverses the promotion effect of HDACis on cisplatin-induced DNA damage and cell apoptosis in ERCC1-high NSCLC cells. In conclusion, this study reveals a novel mechanism by which HDACis re-sensitizes ERCC1-high NSCLC cells to cisplatin via regulation of the E2F1/miR-149/ERCC1 axis, and we propose that combination of HDACis and cisplatin might hold promise to be a more effective therapeutic paradigm for ERCC1-high NSCLCs.

To date, it is still unclear how word structure might impact lexical processing in the brain for languages with an impoverished system of grammatical morphology such as Chinese. In this study, concurrent electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) recordings were performed to inspect the temporal and spatial brain activities that are related to Chinese word structure (compound vs. derivation vs. non-morphological) effects. A masked priming paradigm was utilized on three lexical conditions (compound constitute priming, derivation constitute priming, and non-morphological priming) to tap Chinese native speakers’ structural sensitivity to differing word structures. The compound vs. derivation structure effect was revealed by the behavioral data as well as the temporal and spatial brain activation patterns. In the masked priming task, Chinese derivations exhibited significantly enhanced brain activation in the frontal cortex and involved broader brain networks as compared with lexicalized compounds. The results were interpreted by the differing connection patterns between constitute morphemes within a given word structure from a spreading activation perspective. More importantly, we demonstrated that the Chinese word structure effect showed a distinct brain activation pattern from that of the dual-route mechanism in alphabetic languages. Therefore, this work paved a new avenue for comprehensively understanding the underlying cognitive neural mechanisms associated with Chinese derivations and coordinate compounds.