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Abstract Wheat is a crucial crop worldwide, and accurate detection and counting of wheat spikes are vital for yield estimation and breeding. However, these tasks are daunting in complex field environments. To tackle this, we introduce RIA-SpikeNet, a model designed to detect and count wheat spikes in such conditions. First, we introduce an Implicit Decoupling Detection Head to incorporate more implicit knowledge, enabling the model to better distinguish visually similar wheat spikes. Second, Asymmetric Loss is employed as the confidence loss function, enhancing the learning weights of positive and hard samples, thus improving performance in complex scenes. Lastly, the backbone network is modified through reparameterization and the use of larger convolutional kernels, expanding the effective receptive field and improving shape information extraction. These enhancements significantly improve the model’s ability to detect and count wheat spikes accurately. RIA-SpikeNet outperforms the state-of-the-art YOLOv8 detection model, achieving a competitive 81.54% mAP and 90.29% R2. The model demonstrates superior performance in challenging scenarios, providing an effective tool for wheat spike yield estimation in field environments and valuable support for wheat production and breeding efforts.

Abstract Neural networks are frequently employed to model species distribution through backpropagation methods, known as backpropagation neural networks (BPNN). However, the complex structure of BPNN introduces parameter settings challenges, such as the determination of connection weights, which can affect the accuracy of model simulation. In this paper, we integrated the Grey Wolf Optimizer (GWO) algorithm, renowned for its excellent global search capacity and rapid convergence, to enhance the performance of BPNN. Then we obtained a novel hybrid algorithm, the Grey Wolf Optimizer algorithm optimized backpropagation neural networks algorithm (GNNA), designed for predicting species’ potential distribution. We also compared the GNNA with four prevalent species distribution models (SDMs), namely the generalized boosting model (GBM), generalized linear model (GLM), maximum entropy (MaxEnt), and random forest (RF). These models were evaluated using three evaluation metrics: the area under the receiver operating characteristic curve, Cohen’s kappa, and the true skill statistic, across 23 varied species. Additionally, we examined the predictive accuracy concerning spatial distribution. The results showed that the predictive performance of GNNA was significantly improved compared to BPNN, was significantly better than that of GLM and GBM, and was even comparable to that of MaxEnt and RF in predicting species distributions with small sample sizes. Furthermore, the GNNA demonstrates exceptional powers in forecasting the potential non-native distribution of invasive plant species.

Abstract Background Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis. Methods The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry. Results After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased. Conclusions In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis.

Abstract Emerging and recurrent infectious diseases caused by human coronaviruses (HCoVs) continue to pose a significant threat to global public health security. In light of this ongoing threat, the development of a broad-spectrum drug to combat HCoVs is an urgently priority. Herein, we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment (SELEX). These aptamers have nanomolar affinity with the nucleocapsid protein (NP) of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and also show excellent binding efficiency to the N proteins of both SARS, MERS, HCoV-OC43 and -NL63 with affinity KD values of 1.31 to 135.36 nM. Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant (BA.5) with EC50 values at 2.00 nM and 41.08 nM, respectively. The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs (−229E and -HKU1). In conclusion, we have identified six aptamers with a high pan-coronavirus antiviral activity, which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.

Acquired pure red cell aplasia (aPRCA) is a rare hematological disorder characterized by normochromic, normocytic anemia, reticulocytopenia, and the absence of erythroblasts. The pathogenesis of aPRCA has remained elusive. This review delves into the intricate web of immune mechanisms underlying the development of this enigmatic condition. By exploring immune responses, cytotoxic effects, and antibody-mediated processes, we dissect the immune-driven assault on erythroid progenitors. The classification of aPRCA, including its primary and secondary forms, is elucidated, with a particular emphasis on etiological factors such as viruses, drugs, thymoma, and large granular lymphocytic leukemia. Furthermore, we discuss the implications of cytogenetic changes in erythroid progenitors and immune cells in the pathophysiology of aPRCA. This comprehensive overview aims to shed light on the complex interplay between immune dysregulation and erythroid failure in aPRCA, offering insights that will be crucial for better understanding and treating this disease.

Objective: Current cost-effectiveness analyses of amblyopia screening are mainly from western countries. It remains unclear whether it is cost-effective to implement a preschool amblyopia screening programme in China. Our study aimed to evaluate the cost-effectiveness of a hypothetical kindergarten-based amblyopia screening versus non-screening among 3-year-old children. Methods: We developed a decision tree combined with a Markov model to compare the cost and effectiveness of screening versus non-screening for 3-year-old children from a third-party payment perspective. The primary outcomes were quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER). Costs were obtained from expert opinions in different regions of China. Transition probabilities and health utilities were mainly based on published literature and open sources. Sensitivity analyses were performed to assess the impact of parameters’ uncertainty on results. Results: Base-case analysis demonstrated that the ICER of screening versus non-screening was $17,466/QALY, well below the WTP threshold ($38,223/QALY) for China. One-way sensitivity analysis showed that the prevalence of amblyopia, the transition probability per year from untreated amblyopia to healthy, and the discount rate were the top three factors. The likelihood of cost-effectiveness of screening compared with non-screening was 92.56%, according to probabilistic sensitivity analysis. Scenario analysis also indicated that ICER was lower than the WTP threshold even if the time horizon was shortened or the screening was delayed to the age of 4 or 5. Conclusions: Amblyopia screening could be considered a cost-effective strategy compared to non-screening for 3-year-old children in China. Screening for children at the age of 4 or 5 may even yield better results.

Abstract Alzheimer's disease (AD) is the most prevalent form of dementia, and it displays both clinical and molecular variability. RNA N6-methyladenosine (m6A) regulators are involved in a wide range of essential cellular processes. In this study, we aimed to identify molecular signatures associated with m6A in Alzheimer's disease and use those signatures to develop a predictive model. We examined the expression patterns of m6A regulators and immune features in Alzheimer’s disease using the GSE33000 dataset. We examined the immune cell infiltration and molecular groups based on m6A-related genes in 310 Alzheimer's disease samples. The WGCNA algorithm was utilized to determine differently expressed genes within each cluster. After evaluating the strengths and weaknesses of the random forest model, the support vector machine model, the generalized linear model, and eXtreme Gradient Boosting, the best machine model was selected. Methods such as nomograms, calibration curves, judgment curve analysis, and the use of independent data sets were used to verify the accuracy of the predictions made. Alzheimer's disease and non-disease Alzheimer's groups were compared to identify dysregulated m6A-related genes and activated immune responses. In Alzheimer's disease, two molecular clusters linked to m6A were identified. Immune infiltration analysis indicated substantial variation in protection between groups. Cluster 1 included processes like the Toll-like receptor signaling cascade, positive regulation of chromatin binding, and numerous malignancies; cluster 2 included processes like the cell cycle, mRNA transport, and ubiquitin-mediated proteolysis. With a lower residual and root mean square error and a larger area under the curve (AUC = 0.951), the Random forest machine model showed the greatest discriminative performance. The resulting random forest model was based on five genes, and it performed well (AUC = 0.894) on external validation datasets. Accuracy in predicting Alzheimer's disease subgroups was also shown by analyses of nomograms, calibration curves, and decision curves. In this research, we methodically outlined the tangled web of connections between m6A and AD and created a promising prediction model for gauging the correlation between m6A subtype risk and AD pathology.

Abstract Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC50 = 8.26 μM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 μM (EC50). In comparison with vehicle-treated animals, rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals. At necropsy, nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude. A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center, which were randomized (1:1) to nelfinavir and control groups, showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days (9.0 vs. 14.5 days, P = 0.055) and the duration of fever time by 3.8 days (2.8 vs. 6.6 days, P = 0.014) in mild/moderate COVID-19 patients. The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients, together with its well-established good safety profile in almost all ages and during pregnancy, indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.

Background Obesity may cause insulin resistance (IR), then leads to type 2 diabetes mellitus (T2DM), seriously affecting human health. Irisin is a newly discovered myokine produced by adipose and skeletal muscle tissues, which plays an important role in metabolic regulation. It is worth investigating what changes will occur in serum irisin levels in T2DM patients with overweight or obesity. Objective To examine the abnormality in serum irisin levels in overweight or obese patients with T2DM, and to explore the influencing factors. Methods A total of 119 patients with T2DM who were hospitalized in Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University from December 2019 to June 2021 were selected, including 78 with overweight or obesity and 41 with normal weight assessed by body mass index (BMI). They were compared to 52 healthy people with normal body weight in terms of general demographics, laboratory test indices and serum irisin level. Spearman rank correlation analysis was used to explore the correlation of serum irisin level with demographic and laboratory test indices. Multiple linear regression analysis was used to explore factors associated with the abnormality in serum irisin in overweight or obese T2DM patients. Results Normal-weight diabetics, overweight or obese diabetics and healthy controls had significant differences in levels of systolic blood pressure (SBP), diastolic blood pressure (DBP), BMI, triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) (P

Abstract Aiming at solving the trouble that digital image information is easily intercepted and tampered during transmission, we proposed a color image encryption scheme based on alternate quantum random walk and controlled Rubik’s Cube transformation. At the first, the color image is separated into three channels: channel R, channel G and channel B. Besides, a random sequence is generated by alternate quantum walk. Then the six faces of the Rubik’s Cube are decomposed and arranged in a specific order on a two-dimensional plane, and each pixel of the image is randomly mapped to the Rubik’s Cube. The whirling of the Rubik’s Cube is controlled by a random sequence to realize image scrambling and encryption. The scrambled image acquired by Rubik’s Cube whirling and the random sequence received by alternate quantum walk are bitwise-XORed to obtain a single-channel encrypted image. Finally the three-channel image is merged to acquire the final encrypted image. The decryption procedure is the reverse procedure of the encryption procedure. The key space of this scheme is theoretically infinite. After simulation experiments, the information entropy after encryption reaches 7.999, the NPCR is 99.5978%, and the UACI is 33.4317%. The encryption scheme with high robustness and security has a excellent encryption effect which is effective to resist statistical attacks, force attacks, and other differential attacks.

Klotho (KL) is a renal protein with aging-suppression properties that mediates its regulatory effect during cardiac fibroblast aging. However, to determine whether KL can protect aged myocardial cells by attenuating ferroptosis, this study aimed to investigate the protective effect of KL on aged cells and to explore its potential mechanism. Cell injury of H9C2 cells was induced with D-galactose (D-gal) and treated with KL in vitro. This study demonstrated that D-gal induces aging in H9C2 cells. D-gal treatment increased β-GAL(β-galactosidase) activity, decreased cell viability, enhanced oxidative stress, reduced mitochondrial cristae, and decreased the expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase-4 (GPx4), and P53, which are primary regulators of ferroptosis. The results showed that KL can eliminate D-gal-induced aging in H9C2 cells, likely due to its ability to increase the expression of the ferroptosis-associated proteins SLC7A11 and GPx4. Moreover, pifithrin-α, a P53-specific inhibitor, enhanced the expression of SLC7A11 and GPx4. These results suggest that KL may be involved in D-gal-induced H9C2 cellular aging during ferroptosis, mainly through the P53/SLC7A11/GPx4 signaling pathway.

Abstract To effectively solve the problem of dust pollution caused by the parallel double-belt transportation of coal in a coal preparation plant, taking the Huangyuchuan coal preparation plant as an example, a numerical model of the air flow-dust distribution was established by means of simulation. The flow lines between the strips of tape and the tail of the tape machine will gather, and there will be backflow on the right side of the 3001 tape and left side of the 3002 tape. Under the action of wind current, most of the dust particles larger than 10 μm are distributed in the range of 0–5 m on both sides of the tape; dust particles smaller than 10 μm spread to the entire preparation workshop. Combined with field test verification, dust pollution is mainly concentrated at the guide trough, the feed inlet, the rear of the machine, and the joint of the belt corridor. Based on this, a targeted spray dust reduction treatment plan is proposed. By measuring the dust concentration before and after the treatment of dust-polluted areas, it is proven that the dust reduction efficiency of this plan can reach more than 90%.

Background and Aims. Previous studies have reported a correlation between vitamin D levels and seasonality in healthy populations. However, there are few studies on the seasonal variation in vitamin D levels and its relationship with glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to investigate seasonal changes in serum 25-hydroxyvitamin D [25(OH)D] levels and the associations between these vitamin D concentrations and HbA1c levels in T2DM patients in Hebei, China. Methods. A cross-sectional study of 1,074 individuals with T2DM was conducted from May 2018 to September 2021. Levels of 25(OH)D in these patients were assessed based on both sex and season, and relevant clinical or laboratory variables that could impact vitamin D status were also considered. Results. In the T2DM patient cohort, the mean blood 25(OH)D levels were 17.05 ng/mL. A total of 698 patients (65.0%) had insufficient serum 25(OH)D levels. The vitamin D deficiency rates were significantly higher in the winter and spring compared to the autumn (P

Abstract Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. This pathological pattern, which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens, was significantly correlated with the systemic accumulation of CXCR3+ cells in lungs, spleens, and peripheral blood. Furthermore, the ratio of CXCR3+ to T-box protein expression in T cell (T-bet)+ (CXCR3+/T-bet+ ratio) in CD8+ cells may be used as a predictor of severe COVID-19. These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+ cells in predicting severe COVID-19.

Background The HIV epidemic in key populations such as men who have sex with men (MSM) is a public health issue of worldwide concern. China has seen an increase in newly diagnosed HIV infections through male–male sexual contact in the past decade. In a long-term cohort, how the complex behaviour pattern of MSM changed and the association with the HIV risk are unclear at present.Methods This study was conducted from October 2011 to December 2019 in Tianjin. MSM were recruited by snowball sampling through online and offline ways. Demographic and sexual behavioural data were collected for analysis. Three indicators (condom use in last anal sex, frequency of condom use during anal sex and the number of sexual partners) were used to define the behaviour change. Participants with zero, one, and two or three risk indicators were categorised into behaviour types of ‘protective’, ‘moderate’, and ‘fragile’, respectively. Change in behaviour type between baseline and each visit was considered. Time-varying Cox models were performed to evaluate HIV infection risk.Results Of 2029 MSM included in the study, 127 were new HIV diagnoses. The overall incidence rate was 3.36 per 100 person-years. The percentage of ‘protective’ and ‘moderate’ behaviour types had a conspicuous growth trend as the follow-up. Furthermore, the HIV incidence rate in each visit among different behaviour transition types showed a general downward trend as the number of total follow-up times increased. Individuals who remained in ‘fragile’ (adjusted HR (aHR): 25.86, 95% CI: 6.92 to 96.57) or changed from ‘protective’ to ‘moderate’ (aHR: 4.79, 95% CI: 1.18 to 19.47), ‘protective’ to ‘fragile’ (aHR: 23.03, 95% CI: 6.02 to 88.13), and ‘moderate’ to ‘fragile’ (aHR: 25.48, 95% CI: 6.79 to 95.40) between baseline and the last follow-up had a higher HIV risk. Gained risk indicators were associated with the increase of HIV risk (gained one indicator, aHR: 2.67, 95% CI: 1.68 to 4.24; gained two or three indicators, aHR: 4.99, 95% CI: 3.00 to 8.31) while losing just one risk indicator could halve the risk (aHR: 0.43, 95% CI: 0.21 to 0.90).Conclusions Among MSM in Tianjin, it is necessary to get timely behaviour change for those with high-incidence behaviour patterns while sustaining for those with low-incidence patterns.Trial registration number Chinese Clinical Trials Registry (ChiCTR2000039500).

Objective To study the effect of angelica polysaccharide on proliferation and apoptosis of rat cardiomyocyte line H9c2. Methods Rat cardiomyocyte H9c2 was divided into a control group (Control group), doxorubicin (ADR) induced H9c2 cell replication dilated cardiomyopathy cardiomyocyte group (ADR group), APS intervention (APS group), transfection anti-miR-NC (APS+anti-miR-NC group) and transfected anti-miR-4701-3p(APS+anti-miR-4701-3p group). Flow cytometry was applied to determine apoptosis, Western blot was employed to test B cell lymphoma/leukemia-2(Bcl-2), Bcl-2 related X protein (Bax), nuclear related antigen Ki-67(Ki-67) and proliferation cell nuclear antigen (PCNA) protein expression, enzyme-linked immunoassay (ELISA) method was used to detect B-type brain natriuretic peptide (BNP) level. Cell proliferation was detected by commercially available kit 8(CCK-8), and real-time quantitative PCR (RT-qPCR) was used to analyze the microRNA-4701-3p(miR-4701-3p) expression. Results Adriamycin significantly increased BNP content, apoptosis rate, and Bax protein level in H9c2 cells, and greatly reduced Bcl-2 protein expression(P＜0.05). Angelica polysac-charide obviously increased H9c2 cell viability, Ki-67, PCNA, Bcl-2 protein expression and miR-4701-3p expression after doxorubicin induction, and remarkably reduced cell apoptosis and Bax protein expression(P＜0.05). Knockdown of miR-4701-3p significantly reduced the cell viability, Ki-67, PCNA, and Bcl-2 protein levels of dilated cardiomyopathy H9c2 cells treated with angelica polysaccharide, while significantly increased its apoptosis rate and Bax protein expression(P＜ 0.05). Conclusions Angelica polysaccharide up-regulates the expression of miR-4701-3p, promotes the proliferation of adriamycin-induced rat cardiomyocyte line H9c2.

Spinophilin (SPN) was first isolated from the dendritic spines of neurons as a binding protein of protein phosphatase PP1, it is also known as PPP1R9B. SPN can not only bind to PP1, but also interacts with more than 30 proteins, including cytoskeleton proteins and adhesion molecules. SPN participates in biological processes such as synaptic plasticity, neuronal migration, intracellular signal transduction, and plays an important role in the development of neurodegenerative diseases, psychiatric disorders and neuronal tumors. Therefore, understanding the role and mechanism of SPN in the physiological and pathological processes may support is helpful to advance the basic research and clinical transformation.

Objective To investigate the current situation of improving patient safety and healthcare quality in a tertiary hospital and the understanding of healthcare providers and medical students. Methods A total of 526 valid questionnaires were collected from clinicians, nurses, residents from Peking Union Medical College Hospital(PUMCH) and medical students of Peking Union Medical College(PUMC). Results In the past year, there were 8.2% and 58.8% of the respondents who had experienced medical errors and found potential risks in the clinical process. More than half of respondent's team had reported adverse events, and most of them (75.3%) followed the right way to report. Most people believed hospital authority encouraged reporting medical adverse events, while some of them still worried about potential blame and punishment stemmed from reporting. The results also showed that 88.0% supported development of special curriculum in this field. Some of them had experiences that may have impacts on patient safety in transfer-ring(42.6%)and handover (15.4%), and the majority of people agreed that occupational burnouthas negative impact to patient safety. Almost all the investigation participnts-complained that their emotions and work would be negatively affected if there was a medical error, while 44.5% said that the error also had a positive impact. Conclusions Most of the respondents are relatively satisfied with the current measures of patient safety and quality improvement in PUMCH, but they are still worried about the negative impact on the individuals after the adverse events are reported.

Abstract Background Neutrophils form the first line of innate host defense against invading microorganisms. We previously showed that F0F1 ATP synthase (F-ATPase), which is widely known as mitochondrial respiratory chain complex V, is expressed in the plasma membrane of human neutrophils and is involved in regulating cell migration. Whether F-ATPase performs cellular functions through other pathways remains unknown. Methods Blue native polyacrylamide gel electrophoresis followed by nano-ESI-LC MS/MS identification and bioinformatic analysis were used to identify protein complexes containing F-ATPase. Then, the identified protein complexes containing F-ATPase were verified by immunoblotting, immunofluorescence colocalization, immunoprecipitation, real-time RT-PCR and agarose gel electrophoresis. Immunoblotting, flow cytometry and a LPS-induced mouse lung injury model were used to assess the effects of the F-ATPase-containing protein complex in vitro and in vivo. Results We found that the voltage-gated calcium channel (VGCC) α2δ-1 subunit is a binding partner of cell surface F-ATPase in human neutrophils. Further investigation found that the physical connection between the two proteins may exist between the F1 part (α and β subunits) of F-ATPase and the α2 part of VGCC α2δ-1. Real-time RT-PCR and PCR analyses showed that Cav2.3 (R-type) is the primary type of VGCC expressed in human neutrophils. Research on the F-ATPase/Cav2.3 functional complex indicated that it can regulate extracellular Ca2+ influx, thereby modulating ERK1/2 phosphorylation and reactive oxygen species production, which are typical features of neutrophil activation. In addition, the inhibition of F-ATPase can reduce neutrophil accumulation in the lungs of mice that were intratracheally instilled with lipopolysaccharide, suggesting that the inhibition of F-ATPase may prevent neutrophilic inflammation-induced tissue damage. Conclusions In this study, we identified a mechanism by which neutrophil activity is modulated, with simultaneous regulation of neutrophil-mediated pulmonary damage. These results show that surface F-ATPase of neutrophils is a potential innate immune therapeutic target. Graphical abstract

For the problem of coal dust pollution in the return air lane of the comprehensive mining working face of soft rock mines.Based on the principle of supersonic siphon pneumatic atomization dust control, mobile vehicle-mounted pneumatic spraying combined with full-section fog curtain dust control technology is proposed to address the coal dust pollution problem in the return air tunnel of the comprehensive mining working face of soft rock mines. This technology has a wider spraying range, stronger wind resistance and lower energy consumption.Using the k-ε turbulence module and the fluid flow particle tracking module of COMSOL simulation software, a three-dimensional numerical model of the return air tunnel was established. The effect of wind flow characteristics on the diffusion range of coal dust and fog droplets was analysed, and the dust transport pattern and dust control effect of the new technology were obtained for different cross-sectional return airways. The results show that the velocity of the wind flow is continuously decayed by the slope, and the dust of different particle sizes is distributed differently by the inertial force. Coal dust with particle sizes larger than 6.5 μm accumulates below the structure at a lower velocity, and coal dust with particle sizes smaller than 4.5 μm is mostly suspended above the structure at a higher velocity. The device effectively stops the transport of dust and covers the whole section of the roadway, and the dust removal efficiency reaches 96.53%~97.93%, which provides relevant theoretical support and treatment means for the control of dust pollution in the return airway of coal mines.

To solve the problem of the inability of traditional spray dust removal technology to efficiently restrain dust diffusion at the heading face, a multilayer spiral fog curtain dust control method based on spirally arranged pneumatic nozzles is proposed. In this paper, the k-ɛ turbulence model and K-H droplet breakage model are used. First, different airflow fields are analyzed by simulating the simultaneous injection of different numbers of nozzles, and the motion law of airflow interaction is obtained. Taking the two-layer fog curtain as an example, a multiphysical field coupling numerical simulation of the two-layer spiral fog curtain applied in the field is carried out, and the variation law of its velocity field distribution and particle motion characteristics is analyzed. A similar experimental platform is established to verify the effectiveness of the simulation results and the feasibility of the dust removal scheme. The simulation results show that the double helix arrangement will form a rotating airflow with the cutting arm as the axis to cover the whole roadway section and produce a double-layer spiral fog curtain. The water mist is fragmented into smaller fog droplets under the action of rotating airflow, which improves the dust catching effect of the fog curtain. Experiments show that the dust removal rate and efficiency of multilayer spiral fog curtains are obviously stronger than those of natural dust reduction and traditional spray. After 3 minutes, a dust concentration of approximately 470 mg/m3 can be reduced to less than 4 mg/m3. The average dust removal rates of total dust and exhaled dust were 2.600 mg/(m3.s) and 0.189 mg/(m3.s), respectively, and the dust removal efficiencies were 97.01% and 94.32%.

Text information mining is a key step to data-driven automatic/semi-automatic quality management (QM). For Chinese texts, a word segmentation algorithm is necessary for pre-processing since there are no explicit marks to define word boundaries. Because of intrinsic characteristics of QM-related texts, word segmentation algorithms for normal Chinese texts cannot be directly applied. Hence, based on the analysis of QM-related texts, we summarized six features, and proposed a hybrid Chinese word segmentation model by means of integrating transfer learning (TL), bidirectional long-short term memory (Bi-LSTM), multi-head attention (MA), and conditional random field (CRF) to construct the mTL-Bi-LSTM-MA-CRF model, considering insufficient samples of QM-related texts and excessive cutting of idioms. The mTL-Bi-LSTM-MA-CRF model is composed of two steps. Firstly, based on a word embedding space, the Bi-LSTM is introduced for context information learning, and the MA mechanism is selected to allocate attention among subspaces, and then the CRF is used to learn label sequence constraints. Secondly, a modified TL method is put forward for text feature extraction, adaptive layer weights learning, and loss function correction for selective learning. Experimental results show that the proposed model can achieve good word segmentation results with only a relatively small set of samples.

In order to solve the problem of coal dust pollution at the transfer point, a three-dimensional numerical model of wind flow-coal dust at the loading point of underground rubber run was established by computational fluid dynamics (CFD) discrete particle model and finite element method and k-ε turbulence model, and the coal dust diffusion pollution phenomenon caused by the coal flow transfer under the intersection of wind flow in the cross tunnel was studied. Based on the simulation results of wind flow velocity contour, pressure contour and isochronous flow vector distribution, the influence mechanism of wind flow and coal dust characteristics on the distribution of wind flow and coal dust diffusion in the roadway is analysed, and a dust control and reduction system and treatment scheme with new pneumatic screw spray technology as the core is proposed to suppress coal dust pollution at the reloading point. The results of the study show that the wind flow distribution is mainly influenced by the intersection of tape traction and cross-roadway wind flow, showing a complex multi-layer distribution along the roadway and in the normal direction; the diffusion of coal dust of different particle sizes is influenced by the roadway wind flow, and coal dust with particle sizes in the range of 10μm~20μm is more easily diffused, and the dust with particle sizes in the range of 20μm~45μm is mainly collected and suspended near the vortex wind flow at the cross-roadway. The coal dust in the range of 20 μm~45 μm is more likely to gather in the vortex; the treatment system effectively controls the coal dust inside the dust cover, and the spiral-shaped transported droplet particle group formed by the pneumatic spiral spray combines with it efficiently, which verifies the dust control and reduction effect of the pneumatic spiral spray system at the transfer point, and the dust removal efficiency reaches 89.35%~93.06%, which provides relevant theoretical support for the treatment of dust pollution at the coal transfer point in underground coal mines It provides the theoretical support and means to control dust pollution at underground coal transfer points.

The genus Fritillaria has attracted great attention because of its medicinal and ornamental values. At least three reasons, including the accurate discrimination between various Fritillaria species, protection and sustainable development of rare Fritillaria resources as well as understanding of relationship of some perplexing species, have prompted phylogenetic analyses and development of molecular markers for Fritillaria species. Here we determined the complete chloroplast (CP) genomes for F. unibracteata, F. przewalskii, F. delavayi, and F. sinica through Illumina sequencing, followed by de novo assembly. The lengths of the genomes ranged from 151,076 in F. unibracteata to 152,043 in F. przewalskii. Those CP genomes displayed a typical quadripartite structure, all including a pair of inverted repeats (26,078 to 26,355 bp) separated by the large single-copy (81,383 to 81,804 bp) and small single-copy (17,537 to 17,569 bp) regions. Fritillaria przewalskii, F. delavayi, and F. sinica equivalently encoded 133 unique genes consisting of 38 transfer RNA genes, eight ribosomal RNA genes, and 87 protein coding genes, whereas F. unibracteata contained 132 unique genes due to absence of the rps16 gene. Subsequently, comparative analysis of the complete CP genomes revealed that ycf1, trnL, trnF, ndhD, trnN-trnR, trnE-trnT, trnN, psbM-trnD, atpI, and rps19 to be useful molecular markers in taxonomic studies owning to their interspecies variations. Based on the comprehensive CP genome data collected from 53 species in Fritillaria and Lilium genera, a phylogenomic study was carried out with three Cardiocrinum species and five Amana species as outgroups. The results of the phylogenetic analysis showed that Fritillaria was a sister to Lilium, and the interspecies relationships within subgenus Fritillaria were well resolved. Furthermore, phylogenetic analysis based on the CP genome was proved to be a promising method in selecting potential novel medicinal resources to substitute current medicinal species that are on the verge of extinction.

Aspergillus flavus and the produced aflatoxins cause great hazards to food security and human health across all countries. The control of A. flavus and aflatoxins in grains during storage is of great significance to humans. In the current study, bacteria strain YM6 isolated from sea sediment was demonstrated effective in controlling A. flavus by the production of anti-fungal volatiles. According to morphological characteristics and phylogenetic analysis, strain YM6 was identified as Pseudomonas stutzeri. YM6 can produce abundant volatile compounds which could inhibit mycelial growth and conidial germination of A. flavus. Moreover, it greatly prevented fungal infection and aflatoxin production on maize and peanuts during storage. The inhibition rate was 100%. Scanning electron microscopy further supported that the volatiles could destroy the cell structure of A. flavus and prevent conidia germination on the grain surface. Gas chromatography/mass spectrometry revealed that dimethyl trisulfide (DMTS) with a relative abundance of 13% is the most abundant fraction in the volatiles from strain YM6. The minimal inhibitory concentration of DMTS to A. flavus conidia is 200 µL/L (compound volume/airspace volume). Thus, we concluded that Pseudomonas stutzeri YM6 and the produced DMTS showed great inhibition to A. flavus, which could be considered as effective biocontrol agents in further application.

ABSTRACT: Background: Induction of autoantigen-specific Treg cells that suppress tissue-specific autoimmunity without compromising beneficial immune responses is the holy-grail for immunotherapy to autoimmune diseases. Methods: In a model of experimental autoimmune uveitis (EAU) that mimics human uveitis, ocular inflammation was induced by immunization with retinal antigen interphotoreceptor retinoid-binding protein (IRBP). Mice were given intraperitoneal injection of αCD4 antibody (Ab) after the onset of disease, followed by administration of IRBP. EAU was evaluated clinically and functionally. Splenocytes, CD4+CD25− and CD4+CD25+ T cells were sorted and cultured with IRBP or αCD3 Ab. T cell proliferation and cytokine production were assessed. Findings: The experimental approach resulted in remission of ocular inflammation and rescue of visual function in mice with established EAU. Mechanistically, the therapeutic effect was mediated by induction of antigen-specific Treg cells that inhibited IRBP-driven Th17 response in TGF-β and IL-10 dependent fashion. Importantly, the Ab-mediated immune tolerance could be achieved in EAU mice by administration of retinal autoantigens, arrestin but not limited to IRBP only, in an antigen-nonspecific bystander manner. Further, these EAU-suppressed tolerized mice did not compromise their anti-tumor T immunity in melanoma model. Interpretation: We successfully addressed a specific immunotherapy of EAU by in vivo induction of autoantigen-specific Treg cells without compromising host overall T cell immunity, which should have potential implication for patients with autoimmune uveitis. Funding: This study was supported by the Natural Science Foundation of Guangdong Province and the Fundamental Research Fund of the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center.

The distribution of multiscale pores and fractures in coal and rock is an important basis for reflecting the capacity of fluid flow in coal seam seepage passages. Accurate extraction and qualitative and quantitative analysis of pore-fracture structures are helpful in revealing the flow characteristics of fluid in seepage channels. The relationship between pore and fracture connectivity can provide a scientific reference for optimizing coal seam water injection parameters. Therefore, to analyse the change in permeability caused by the variability in the coal pore-fracture network structure, a CT scanning technique was used to scan coal samples from the Leijia District, Fuxin. A total of 720 sets of original images were collected, a median filter was used to filter out the noise in the obtained images, and to form the basis of a model, the reconstruction and analysis of the three-dimensional pore-fracture morphology of coal samples were carried out. A pore-fracture network model of the coal body was extracted at different scales. Using the maximum sphere algorithm combined with the coordination number, the effect of different quantitative relationships between pore size and pore throat channel permeability was studied. Avizo software was used to simulate the flow path of fluid in the seepage channels. The change trend of the fluid velocity between different seepage channels was discussed. The results of the pore-fracture network models at different scales show that the pore-fracture structure is nonuniform and vertically connected, and the pores are connected at connecting points. The pore size distribution ranges from 104 μm to 9425 μm. The pore throat channel length distribution ranges from 4206 μm to 48073 μm. The size of the coordination number determines the connectivity and thus the porosity of the coal seam. The more connected pore channels there are, the larger the pore diameters and the stronger the percolation ability. During flow in the seepage channels of the coal, the velocity range is divided into a low-speed region, medium-speed region and high-speed region. The fluid seepage in the coal seam is driven by the following factors: pore connectivity > pore and pore throat dimensions > pore and pore throat structure distribution. Ultimately, the pore radius and pore connectivity directly affect the permeability of the coal seam.

Rice-crab culture is the characteristic rice ecological breeding model used in the Panjin area of Liaohe River Basin, China, and it can improve the ecological environment and create increased economic benefits. From a food perspective, both rice yield and quality, which are closely related to the fertilization mode, should be considered. However, the effect of different fertilization modes on rice quality has not been comprehensively investigated in this co-culture system. This study investigated the effects of three fertilization modes(FP1, FP2, and OPT) divided according to different fertilization types and methods on rice yield and quality, and set up a non-fertilized control group. In the rice-crab culture system, FP2 used fewer fertilizers and had a lower economic cost, and the yield was only slightly less than that of OPT(highest yield) but there was no statistical difference. FP2 elicited the best appearance quality and better cooking and eating quality among all treatment modes. Compared with CK, three fertilization modes significantly increased the protein content in rice and decreased the amylose content, which would lead to the deterioration of rice eating quality. However FP2 had the least protein increase and the least amylose reduction. There was no significant change in crude fat and starch content. Therefore, the FP2 fertilization mode was the best choice for the rice-crab culture system, as it significantly improved rice yield and increased rice quality at a relatively low cost.

Objective(s): -methyl-D-aspartate NMDA receptor (NMDAR) and aquaporin 4 (AQP4) are involved in the molecular cascade of edema after traumatic brain injury (TBI) and are potential targets of studies in pharmacology and medicine. However, their association and interactions are still unknown.Materials and Methods: We established a rat TBI model in this study. The cellular distribution patterns of AQP4 after inhibition of NMDAR were determined by Western blotting and immunoreactive staining. Furthermore, the regulation of NMDA receptor 1 by AQP4 was studied by injection of a viral vector targeting AQP4 by RNAi into the rat brain before TBI.Results: The results suggest that AQP4 protein expression increased significantly (P

Background: Current methods of lymph node (LN) staging are controversial in predicting the survival of SBA. We aimed to develop an alternative LN-classification-based nomogram to individualize SBA prognosis. Methods: Based on the data from the Surveillance, Epidemiology, and End Results (SEER) database of patients diagnosed with SBA between 2004 and 2014, we identified the cut-off points for the number of LNs examined and the number found to be metastatic using the K-adaptive partitioning (KAPS) algorithm. Using metastatic LNs, a nomogram predicting the survival of SBA was derived, internally and externally validated, and measured by calibration curve, C-index, and decision curve analysis (DCA), and compared to the 8th TNM stage. Results: A total of 1516 patients were included. The cut-off of 17 was the optimal examined LN number. For metastatic LN numbers, the cut-off points were 0, 2, and 8. The C-index for the nomogram was higher than the 8th TNM staging (internal: 0.734; 95% CI, 0.693 to 0.775 vs. 0.677; 95% CI, 0.652 to 0.702, P 8 metastatic LNs and set the least examined LN number to 17. A nomogram based on this staging showed great clinical usability than TNM staging for predicting the survival of SBA patients. Keywords: Small bowel carcinoma, Metastatic lymph node, Survival predicting model, TNM staging

Objective: With the evolution of society and changes in human lifestyle, obesity is becoming increasingly prevalent worldwide, and obesity-related comorbidities such as diabetes, hyperlipidemia, hypertension, and coronary heart disease are more common. As a result, new devices and methods for bariatric and metabolic endoscopy are being developed for clinical use, offering new options for patients. This review discussed the progress in bariatric and metabolic endoscopy. Data Sources: This review was based on data in articles published in the PubMed database up to September 2017, with the following keywords: “obesity”, “endoscopy”, “weight loss”, and “metabolism”. Study Selection: Original articles about various endoscopic methods of weight loss and other reviews of bariatric and metabolic endoscopy were included and analyzed. Results: The technology of bariatric and metabolic endoscopy has advanced rapidly in recent years. The intragastric balloon (IGB), with its comparatively long period of development, is the most mature and widely used instrument. Multiple new endoscopic devices have been created in recent years, with different targets to achieve weight loss. Despite the proliferation of new devices, the lack of clinical data results in a shortage of clinical experience and instruction in the use of this new equipment. Conclusions: Bariatric and metabolic endoscopy would help obese people lose weight or prepare for bariatric surgery and hopefully alleviate some of the complications of bariatric procedures. Adequate studies and data are still needed for the new endoscopic devices.

Abstract During microbial electrosynthesis (MES) driven CO2 reduction, cathode plays a vital role by donating electrons to microbe. Here, we exploited the advantage of reduced graphene oxide (RGO) paper as novel cathode material to enhance electron transfer between the cathode and microbe, which in turn facilitated CO2 reduction. The acetate production rate of Sporomusa ovata-driven MES reactors was 168.5 ± 22.4 mmol m−2 d−1 with RGO paper cathodes poised at −690 mV versus standard hydrogen electrode. This rate was approximately 8 fold faster than for carbon paper electrodes of the same dimension. The current density with RGO paper cathodes of 2580 ± 540 mA m−2 was increased 7 fold compared to carbon paper cathodes. This also corresponded to a better cathodic current response on their cyclic voltammetric curves. The coulombic efficiency for the electrons conversion into acetate was 90.7 ± 9.3% with RGO paper cathodes and 83.8 ± 4.2% with carbon paper cathodes, respectively. Furthermore, more intensive cell attachment was observed on RGO paper electrodes than on carbon paper electrodes with confocal laser scanning microscopy and scanning electron microscopy. These results highlight the potential of RGO paper as a promising cathode for MES from CO2.

Abstract Chronic intestinal pseudo-obstruction (CIPO) is a rare intestinal motility disorder with significant morbidity and mortality in pediatric patients. The diagnosis of CIPO is difficult, because it is clinically based on the symptoms and signs of bowel obstruction which are similar to the clinical manifestations of other gastrointestinal diseases like short bowel syndrome (SBS). Therefore, it is desirable to identify and establish new laboratory diagnostic markers for CIPO that are reliable and easily accessible. In our study we have identified the ratio of the urinary glutamine and glutamic acid as a promising biomarker for distinguishing suspected CIPO cases and simple SBS cases. The area under ROC curve was 0.83, at cutoff value = 7.04 with sensitivity of 65% and specificity of 92%.

Platycladus orientalis L. (Cupressaceae) has a lifespan of thousands of years. Ancient trees have very high scientific, economic and cultural values. The senescence of ancient trees is a new research area but is poorly understood. Leaves are the primary and the most sensitive organ of a tree. To understand leaf structural response to tree senescence in ancient trees, experiments investigating the morphology, anatomy and ultrastructure were conducted with one-year leaves of ancient P. orientalis (ancient tree >2,000 years) at three different tree senescent levels (healthy, sub-healthy and senescent) at the world’s largest planted pure forest in the Mausoleum of Yellow Emperor, Shaanxi Province, China. Observations showed that leaf structure significantly changed with the senescence of trees. The chloroplast, mitochondria, vacuole and cell wall of mesophyll cells were the most significant markers of cellular ultrastructure during tree senescence. Leaf ultrastructure clearly reflected the senescence degree of ancient trees, confirming the visual evaluation from above-ground parts of trees. Understanding the relationships between leaf structure and tree senescence can support decision makers in planning the protection of ancient trees more promptly and effectively by adopting the timely rejuvenation techniques before the whole tree irreversibly recesses.

PurposePharmacokinetic models facilitate assessment of properties of the micro-vascularization based on DCE-MRI data. However, accurate pharmacokinetic modeling in the liver is challenging since it has two vascular inputs and it is subject to large deformation and displacement due to respiration.MethodsWe propose an improved pharmacokinetic model for the liver that (1) analytically models the arrival-time of the contrast agent for both inputs separately; (2) implicitly compensates for signal fluctuations that can be modeled by varying applied flip-angle e.g. due to B1-inhomogeneity. Orton's AIF model is used to analytically represent the vascular input functions. The inputs are independently embedded into the Sourbron model. B1-inhomogeneity-driven variations of flip-angles are accounted for to justify the voxel's displacement with respect to a pre-contrast image.ResultsThe new model was shown to yield lower root mean square error (RMSE) after fitting the model to all but a minority of voxels compared to Sourbron's approach. Furthermore, it outperformed this existing model in the majority of voxels according to three model-selection criteria.ConclusionOur work primarily targeted to improve pharmacokinetic modeling for DCE-MRI of the liver. However, other types of pharmacokinetic models may also benefit from our approaches, since the techniques are generally applicable.

Background: Esophageal cancer is the sixth leading cause of cancer-related death worldwide. Pentraxin-3 (PTX3) is a member of the PTX superfamily. Here, we investigated the role of PTX3 in esophageal squamous cell carcinoma (ESCC). Methods: The effect of PTX3 on ESCC cell proliferation, colony formation, apoptosis, migration, and invasion was investigated using cell viability assays, colony formation assays, flow cytometry, and migration and invasion assays. The effect of PTX3 on the tumorigenicity of ESCC in vivo was investigated with xenograft studies in nude mice. Results: PTX3 overexpression in ESCC cells reduced cellular proliferation and colony formation (P < 0.05) and increased the rate of apoptosis (P < 0.05). PTX3 expression had no significant effect on the migratory or invasive potential of ESCC cells. In our mouse model of human ESCC, we achieved 100% successful tumor establishment. Compared with the control and empty vector-expressing groups, the PTX3-expressing group formed significantly smaller tumors (P < 0.05). Conclusions: This study indicates that PTX3 might play an inhibitory role in ESCC.

Schizophrenia (SCZ) is a severe psychiatric disorder with evidence of a strong genetic component in the complex etiologies. Some studies indicated that gamma-aminobutyric acid (GABA)A receptor β2 subunit gene (GABRB2) was associated with SCZ. Other studies reported a negative association. Moreover, the results of two previous meta-analyses of GABRB2 with SCZ were inconsistent and the sample sizes were limited. Therefore, an updated meta-analysis combined with genome-wide association study (GWAS) data of the Han Chinese population and Psychiatric Genomics Consortium (PGC) was performed. Available case-control and family-based genetic data were extracted from association studies, and the GWAS data were included. The findings showed no association between six single-nucleotide polymorphisms of GABRB2 (rs6556547, rs1816071, rs1816072, rs194072, rs252944, and rs187269) and SCZ in a total of 51,491 patients and 74,667 controls. The ethnic subgroup analysis revealed no significant association in Asian populations. Since the PGC data of SCZ (SCZ-PGC, 2014) contained 3 studies of Asian populations (1866 patients and 3418 controls), only the data of European samples in SCZ-PGC were used for the meta-analysis of the Caucasian population in the present study. The result still showed no association in the Caucasian population. In conclusion, the present meta-analysis on combined data from GWASs of the Han Chinese population and PGC suggested that GABRB2 polymorphisms might not be associated with SCZ.