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Introduction: Although programmed death ligand 1 (PD-L1) inhibitor plus chemotherapy regimen is a promising strategy for malignant tumors, it can induce significant immune-related adverse events, such as immune-related pneumonitis. Here, we report the first case of lethal immune-related pneumonitis in an Asian patient receiving anti-PD-L1 treatment. Case Presentation: A 68-year-old man was diagnosed with small cell lung cancer and interstitial pneumonia. After his pulmonary infection was relieved by comprehensive treatment, the patient received first-line treatment with durvalumab plus etoposide and carboplatin. Two weeks after starting durvalumab treatment, the patient had chest pain and shortness of breath. He was diagnosed with immune-induced pneumonia and treated with methylprednisolone, cefoperazone, and sulbactam, followed by oxygen and pirfenidone. Oxygen partial pressure decreased to 58 mm Hg within next the 4 days and laboratory assessment suggested cytokine storm. The patient underwent 2 plasma exchanges, one double filtration plasmapheresis and oxygen saturation decreased continuously. The patient died 1 month after durvalumab treatment. Conclusion: Immune-related pneumonitis induced by PD-L1 inhibitors is rare but life-threatening. Infection should be ruled out before starting immunotherapy.

Abstract Improving access to HIV/AIDS healthcare services is of great concern to government and policymakers striving to strengthen overall public health. How to reasonably allocate HIV/AIDS healthcare resources and maximize the equality of access to healthcare services across subdistrict areas has become an urgent problem to be solved. However, there is limited research on this topic in China. It is necessary to evaluate spatial accessibility to improve the accessibility and equity of HIV/AIDS healthcare services. In this study, the improved multi-modal two-step floating catchment area (2SFCA) and inverted 2SFCA (i2SFCA) methods are used to measure the spatial accessibility of HIV/AIDS healthcare services and the crowdedness of the healthcare sites in Shandong Province, China. Then, the theoretical supply and the optimal spatial distribution of resources are calculated and visualized by minimizing the accessibility gaps between demand locations. This study showed that the spatial accessibility of HIV/AIDS service resources in Shandong Province was concentrated and unevenly distributed, and the accessibility scores in the marginal areas of prefecture-level cities were significantly lower than those in other areas. Regions with a large number of doctors had significantly higher levels of spatial accessibility. The ART accessibility scores in the southwest of Shandong Province were higher than those in other regions. As the travel friction coefficient increased, the accessibility scores formed an approximately circular cluster distribution centered on the healthcare sites in geographical distribution. More ART drugs needed to be supplied in marginal areas and more doctors were needed to work on HIV/AIDS in urban areas to address the spatial distribution imbalance of HIV/AIDS healthcare services. This study profoundly analyzed the spatial accessibility of HIV/AIDS healthcare services and provided essential references for decision-makers. In addition, it gives a significant exploration for achieving the goal of equal access to HIV/AIDS healthcare services in the future.

Many biological studies show that microRNAs (miRNAs) play an indispensable role in the regulation of various biological processes. MiRNAs are significant biomakers in disease diagnosis, aiding in the understanding of pathogenesis and facilitating the identification, diagnosis, and treatment of various diseases. However, the exact mechanism by which miRNAs influence the development of these diseases remains incompletely understood. Thus, it is crucial to develop a computational method to identify unknown miRNA-disease associations. In this study, we designed a computational framework based on singular value decomposition (SVD) and node2vec to predict unknown miRNA-disease associations (SNMDA). We use SVD technique to extract the linear features of miRNAs and diseases. The node2vec method is applied to learn the non-linear embeddings of miRNAs and diseases. We combine the linear feature and non-linear feature to get a new feature vector and feed it into the Gradient Boosting (GB) classifier for binary classification prediction. According to the experimental findings, SNMDA demonstrated an average area under the curve (AUC) of 0.9608 during five-fold cross-validation. Compared with the other Cutting-edge methods, SNMDA achieved the highest AUC value. Furthermore, the case studies on gastric cancer, malignant esophageal lesions, and lung tumors validate the effectiveness of SNMDA. The comprehensive experimental results demonstrate that SNMDA is effective in identifying unknown miRNA-disease associations.

Arbuscular mycorrhizal fungi (AMF) play a key role in regulating the carbon cycle in terrestrial ecosystems. However, there is little information on how AMF inoculation affects the carbon fluxes of paddy fields, which are major sources of global carbon emissions. We, therefore, designed an experiment to study the effects of AMF inoculation on methane and carbon dioxide emissions from a paddy field. Results showed that: (1) Among the tested factors, the C/N ratio was the main environmental determinant of microbial community structure in the investigated soil; (2) compared with traditional fertilisation (control), the soil C/N ratio increased by 2.1~15.2% and 1.4~10.5% as a result of AMF application alone (M) or in combination with mineral fertiliser (FM) throughout the growing season, respectively. This change shifted microbial community composition to higher G+/G- bacterial and fungal/bacterial ratios; (3) the microbial community change favoured soil carbon retention. Methane (CH4) emission peaks were reduced by 59.4% and 76.0% versus control in the M treatment and by 52.5% and 29.4% in the FM treatment in the midseason and end-of-season drainage periods, and CO2 emission peaks were reduced by 70.1% and 52.3% in the M plots and by 55.4% and 66.4% in the FM plots.

BackgroundMaternal immune activation (MIA) is a mature means to construct a schizophrenia model. However, some preclinical studies have reported that a MIA-induced schizophrenia model seemed to have gender heterogeneity in behavioral phenotype. On the other hand, the MIA’s paradigms were diverse in different studies, and many details could affect the effect of MIA. To some extent, it is not credible and scientific to directly compare the gender differences of different MIA programs. Therefore, it is necessary to study whether the sex of the exposed offspring leads to behavioral differences on the premise of maintaining a consistent MIA mode.MethodsAn animal model of schizophrenia was established by the administration of 10 mg/kg Poly (I: C) when dams were on day 9 of gestation. Then, a number of female and male offspring completed a series of behavioral tests during postnatal days 61–75.ResultsCompared with the female control group (n = 14), female MIA offspring (n = 12) showed a longer movement distance (d = 1.07, p < 0.05) and higher average speed (d = 1.08, p < 0.05) in the open field test (OFT). In the Y maze test, the percentage of entering the novel arm of female MIA offspring was lower (d = 0.92, p < 0.05). Compared with the male control group (n = 14), male MIA offspring (n = 13) displayed less movement distance (d = 0.93, p < 0.05) and a lower average speed (d = 0.94, p < 0.05) in the OFT. In the Y maze test, the proportion of exploration time in the novel arm of male MIA offspring was lower (d = 0.96, p < 0.05). In the EPM, male MIA offspring showed less time (d = 0.85, p < 0.05) and a lower percentage of time spent in the open arms (d = 0.85, p < 0.05). Male MIA offspring also had a lower PPI index (76 dB + 120 dB, d = 0.81, p < 0.05; 80 dB + 120 dB, d = 1.45, p < 0.01).ConclusionsOur results showed that the behavioral phenotypes induced by prenatal immune activation were highly dependent on the sex of the offspring.

The occurrence of hand, foot, and mouth disease (HFMD) is closely related to meteorological factors. However, location-specific characteristics, such as persistent air pollution, may increase the complexity of the impact of meteorological factors on HFMD, and studies across different areas and populations are largely lacking. In this study, a two-stage multisite time-series analysis was conducted using data from 16 cities in Shandong Province from 2015 to 2019. In the first stage, we obtained the cumulative exposure–response curves of meteorological factors and the number of HFMD cases for each city. In the second stage, we merged the estimations from the first stage and included city-specific air pollution variables to identify significant effect modifiers and how they modified the short-term relationship between HFMD and meteorological factors. High concentrations of air pollutants may reduce the risk effects of high average temperature on HFMD and lead to a distinct peak in the cumulative exposure-response curve, while lower concentrations may increase the risk effects of high relative humidity. Furthermore, the effects of average wind speed on HFMD were different at different levels of air pollution. The differences in modification effects between subgroups were mainly manifested in the diversity and quantity of significant modifiers. The modification effects of long-term air pollution levels on the relationship between sunshine hours and HFMD may vary significantly depending on geographical location. The people in age＜3 and male groups were more susceptible to long-term air pollution. These findings contribute to a deepening understanding of the relationship between meteorological factors and HFMD and provide evidence for relevant public health decision-making.

Infrared ship detection is of great significance due to its broad applicability in maritime surveillance, traffic safety and security. Multiple infrared sensors with different spectral sensitivity provide enhanced sensing capabilities, facilitating ship detection in complex environments. Nevertheless, current researches lack discussion and exploration of infrared imagers in different spectral ranges for marine objects detection. Furthermore, for unmanned marine vehicles (UMVs), e.g., unmanned surface vehicles (USVs) and unmanned ship (USs), detection and perception are usually performed in embedded devices with limited memory and computation resource, which makes traditional convolutional neural network (CNN)-based detection methods struggle to leverage their advantages. Aimed at the task of sea surface object detection on USVs, this paper provides lightweight CNNs with high inference speed that can be deployed on embedded devices. It also discusses the advantages and disadvantages of using different sensors in marine object detection, providing a reference for the perception and decision-making modules of USVs. The proposed method can detect ships in short-wave infrared (SWIR), long-wave infrared (LWIR) and fused images with high-performance and high-inference speed on an embedded device. Specifically, the backbone is built from bottleneck depth-separable convolution with residuals. Generating redundant feature maps by using cheap linear operation in neck and head networks. The learning and representation capacities of the network are promoted by introducing the channel and spatial attention, redesigning the sizes of anchor boxes. Comparative experiments are conducted on the infrared ship dataset that we have released which contains SWIR, LWIR and the fused images. The results indicate that the proposed method can achieve high accuracy but with fewer parameters, and the inference speed is nearly 60 frames per second (FPS) on an embedded device.

In tumor treatment, the highly disordered vascular system and lack of accumulation of chemotherapeutic drugs in tumors severely limit the therapeutic role of nanocarriers. Smaller drug-containing nanoparticles (NPs) can better penetrate the tumor but are easily removed, which severely limits the tumor-killing properties of the drug. The chemotherapeutic medication doxorubicin (DOX) is highly toxic to the heart, but this toxicity can be effectively mitigated and the combined anticancer effect can be enhanced by clinically incorporating curcumin (CUR) as part of the dual therapy. We designed a small-molecule peptide, Pep1, containing a targeting peptide (CREKA) and a pH-responsive moiety. These NPs can target the blood vessels in tumor microthrombi and undergo a morphological shift in the tumor microenvironment. This process enhances the penetration and accumulation of drugs, ultimately improving the effectiveness of cancer treatment. In vitro and in vivo experiments demonstrated that this morphological transformation allowed rapid and effective drug release into tumors, the effective inhibition of tumor angiogenesis, and the promotion of tumor cell apoptosis, thus effectively killing tumor cells. Our findings provide a novel and simple approach to nhibit the growth and metastasis of hepatocellular carcinoma.

Abstract Background Gallbladder carcinoma (GBC) is a highly malignant tumor with a poor overall prognosis. This study aimed to identify the characteristic microRNAs (miRNAs) of GBC and the competing endogenous RNA (ceRNA) regulatory mechanisms. Methods The microarray data of GBC tissue samples and normal gallbladder (NGB) tissue samples from the Gene Expression Omnibus (GEO) database was downloaded. GBC-related differentially expressed miRNAs (DE-miRNAs) were identified by inter-group differential expression analysis and weighted gene co-expression network analysis (WGCNA). Machine learning algorithms were used to screen the characteristic miRNA based on the intersect between least absolute shrinkage and selection operator (LASSO) and Support vector machine-recursive feature elimination (SVM-RFE). Based on the differential expression analysis of GEO database, the ceRNA network of characteristic miRNA was predicted and constructed. The biological functions of the ceRNA network were revealed by carrying out the gene enrichment analysis was implemented. We further screened the key genes of ceRNA network and constructed a protein-protein interaction (PPI) network, and predicted and generated the transcription factors (TFs) network of signature miRNAs. The expression of characteristic miRNA in clinical samples was verified by quantitative real-time polymerase chain reaction (qRT-PCR). Results A total of 131 GBC-related DE-miRNAs were obtained. The hsa-miR-4770 was defined as characteristic miRNA for GBC. The ceRNA network containing 211 mRNAs, one miRNA, two lncRNAs, and 48 circRNAs was created. Gene enrichment analysis suggested that the downstream genes were mainly involved in actin filament organization, cell-substrate adhesion, cell-matrix adhesion, reactive oxygen species metabolic process, glutamine metabolic process and extracellular matrix (ECM)-receptor interaction pathway. 10 key genes in the network were found to be most correlated with disease, and involved in cell cycle-related processes, p53, and extrinsic apoptotic signaling pathways. The qRT-PCR result demonstrated that hsa-miR-4770 is down-regulated in GBC, and the expression trend is consistent with the public database. Conclusions We identified hsa-miR-4770 as the characteristic miRNA for GBC. The ceRNA network of hsa-miR-4770 may play key roles in GBC. This study provided some basis for potential pathogenesis of GBC.

With the rapid advancement of wireless communication technology, automatic modulation classification (AMC) plays a crucial role in drone communication systems, ensuring reliable and efficient communication in various non-cooperative environments. Deep learning technology has demonstrated significant advantages in the field of AMC, effectively and accurately extracting and classifying modulation signal features. However, existing deep learning models often have high computational costs, making them difficult to deploy on resource-constrained drone communication devices. To address this issue, this study proposes a lightweight Mobile Automatic Modulation Classification Transformer (MobileAmcT). This model combines the advantages of lightweight convolutional neural networks and efficient Transformer modules, incorporating the Token and Channel Conv (TCC) module and the EfficientShuffleFormer module to enhance the accuracy and efficiency of the automatic modulation classification task. The TCC module, based on the MetaFormer architecture, integrates lightweight convolution and channel attention mechanisms, significantly improving local feature extraction efficiency. Additionally, the proposed EfficientShuffleFormer innovatively improves the traditional Transformer architecture by adopting Efficient Additive Attention and a novel ShuffleConvMLP feedforward network, effectively enhancing the global feature representation and fusion capabilities of the model. Experimental results on the RadioML2016.10a dataset show that compared to MobileNet-V2 (CNN-based) and MobileViT-XS (ViT-based), MobileAmcT reduces the parameter count by 74% and 65%, respectively, and improves classification accuracy by 1.7% and 1.09% under different SNR conditions, achieving an accuracy of 62.93%. This indicates that MobileAmcT can maintain high classification accuracy while significantly reducing the parameter count and computational complexity, clearly outperforming existing state-of-the-art AMC methods and other lightweight deep learning models.

Background. Diabetes self-management education (DSME) provides diabetic patients with knowledge of diabetes, requires attention and recording of dietary habits, and increases the frequency and accuracy of blood glucose monitoring. DSME also achieves better blood glucose control, thus benefiting diabetic patients and reducing the risk of diabetes complications. However, few studies have systematically examined whether DSME follows AADE 7 Self-Care Behaviors (AADE7™). Therefore, this study aimed to investigate the control effect of AADE7™-based management on laboratory test indicators of diabetic patients. Methods. The patients with diabetes who received shared care management in our hospital between June 2014 and April 2022 were analyzed retrospectively. According to the process of outpatient consultation, each patient received health education provided by diabetes education nurses and dietitians after consultation. Health education was a process from assessment to health guidance. The basic information of all patients was recorded, and AADE7™ behavior assessment and health education session were conducted through interviews. A total of 13,650 were given shared care management, requiring more than 6 follow-up visits per year, as well as health education. It was reassessed annually according to AADE standards. The impact of the patients’ behavior change after the AADE7™-based management on the relevant test indicators was observed. Results. After eight years of intervention, a total of 8319 samples were obtained after excluding the outliers. Stepwise regression analysis was performed, and the results showed that, with other conditions held constant, a greater number of days per week to follow a healthy diet, to take hypoglycemic medication as prescribed, to monitor blood glucose, and to exercise and higher education level were associated with lower levels of glycosylated hemoglobin. The change from drinking to nondrinking was associated with lower triglycerides. If low blood glucose was monitored, patients who reviewed and took immediate action showed lower levels of low-density lipoprotein, urine microalbumin, and urine microalbumin/creatinine ratio compared with those without review and immediate action. Significance tests for each term showed P value

Background Gastric cancer (GC) stem cells play an important role in GC progression. Circular RNAs (circRNAs) act as microRNA (miRNA) sponges and inhibit the biological function of miRNAs in GC cytoplasm. MiRNAs also participate in GC progress. circ_0051246 was shown to be associated with miR-375 after analyzing GC microarray data GSE78091 and GSE83521. The oncoprotein Yes-associated protein 1 (YAP1) is targeted by miR-375 and can be inactivated via the Hippo tumor suppressor pathway. Due to insufficient research on circ_0051246, this study aimed to investigate its relationship with miR-375 and YAP1 in cancer stem cells (CSCs). Methods SGC-7901 CSCs were used to establish knockdown/overexpression models of circ_0051246, miR-375, and YAP1. Malignant phenotypes of CSCs were assessed using Cell Counting Kit 8, colony/sphere formation, 5-Ethynyl-2′-deoxyuridine assay, flow cytometry, Transwell, and wound healing assays. To detect the interactions between circ_0051246, miR-375, and YAP1 in CSCs, a dual-luciferase reporter assay and fluorescence in situ hybridization were performed. In addition, 24 BALB/c nude mice were used to establish orthotopic xenograft tumor models. Four groups of mice were injected with CSCs (1 × 106 cells/100 µL) with circ_0051246 knockdown, miR-375 overexpression, or their respective control cells, and tumor progression and gene expression were observed by hematoxylin-eosin staining, immunohistochemistry. Western blot and quantitative real-time PCR were utilized to examine protein and gene expression, respectively. Results Circ_0051246 silencing reduced viability, promoted apoptosis, and inhibited proliferation, migration and invasion of CSCs. The functional effects of miR-375 mimics were comparable to those of circ_0051246 knockdown; however, the opposite was observed after miR-375 inhibitors treatment of CSCs. Furthermore, circ_0051246-overexpression antagonized the miR-375 mimics’ effects on CSCs. Additionally, YAP1 overexpression promoted CSC features, such as self-renewal, migration, and invasion, inhibited apoptosis and E-cadherin levels, and upregulated the expression of N-cadherin, vimentin, YAP1, neurogenic locus notch homolog protein 1, and jagged canonical notch ligand 1. Conversely, YAP1-silenced produced the opposite effect. Moreover, miR-375 treatment antagonized the malignant effects of YAP1 overexpression in CSCs. Importantly, circ_0051246 knockdown and miR-375 activation suppressed CSC tumorigenicity in vivo. Conclusion This study highlights the promotion of circ_0051246-miR-375-YAP1 axis activation in GC progression and provides a scientific basis for research on the molecular mechanism of CSCs.

Abstract Background The high prevalence of depression among older people in China places a heavy burden on the health system. Multimorbidity, mobility limitation and subjective memory impairment are found to be risk indicators for depression. However, most studies on this topic focused on depression at a single point in time, ignoring the dynamic changes in depressive symptoms and the relationship between the trajectories and these three conditions. Therefore, we aimed to identify distinct trajectories of depressive symptoms in older people and investigate their associations with multimorbidity, mobility limitation and subjective memory impairment. Methods Data was drawn from China Health and Retirement Longitudinal Study conducted during 2011–2018. A total of 5196 participants who completed 4 visits, conducted every 2–3 years were included in this study. Group-based trajectory modeling was conducted to identify distinct trajectories of depressive symptoms z-scores. Multinomial logistic regression was used to investigate the relationships. Results Four distinct trajectories of depressive symptoms z-scores were identified, labeled as persistently low symptoms (68.69%, n = 3569), increasing symptoms (12.14%, n = 631), decreasing symptoms (14.05%, n = 730) and persistently high symptoms (5.12%, n = 266). Participants with multimorbidity had unfavorable trajectories of depressive symptoms compared with those without multimorbidity, with adjusted odds ratios (95% CIs) of 1.40 (1.15, 1.70), 1.59 (1.33, 1.90) and 2.19 (1.65, 2.90) for the increasing symptoms, decreasing symptoms and persistently high symptoms, respectively. We also observed a similar trend among participants with mobility limitations. Compared with participants who had poor subjective memory, participants with excellent/very good/good subjective memory had a lower risk of developing unfavorable trajectories of depressive symptoms. The adjusted odds ratios (95% CIs) of the increasing symptoms, decreasing symptoms and persistently high symptoms were 0.54 (0.40, 0.72), 0.50 (0.38, 0.65) and 0.48 (0.31, 0.73), respectively. Conclusions Multimorbidity, mobility limitation and subjective memory impairment were found to be potential risk factors for unfavorable depression trajectories.

Abstract Background Postoperative insulin resistance (PIR) represents an important characteristic of metabolic response following surgical injury. Clinical outcomes are negatively correlated to postoperative insulin resistance and hyperglycemia, indicating a novel treatment for reducing postoperative insulin resistance is urgently needed. The current work aimed to assess the protective effects of branched-chain amino acids (BCAA) on glucose metabolism disorders induced surgically in a rat model, and to explore the underpinning mechanism. Methods and results Rats were randomly assigned to 2 groups, including the control and BCAA groups. Rats were given a compulsory oral 3 mL load by gavage two hours before surgery. The results showed that BCAA remarkably reduced glycemia by suppressing liver gluconeogenesis via reduction of cAMP-response element-binding protein-regulated transcription coactivator 2 (CRTC2) and glucose-6-phosphatase (G6PC) gene and protein expression levels (all Ps

BTB/POZ domain-containing protein 7 (BTBD7) has a relative molecular weight of 126KD and contains two conserved BTB/POZ protein sequences. BTBD7 has been shown to play an essential role in normal human development, precancerous lesions, heat-stress response, and tumor progression. BTBD7 promotes branching morphogenesis during development and participates in the salivary gland, lung, and tooth formation. Furthermore, many studies have shown that aberrant expression of BTBD7 promotes heat stress response and the progression of precancerous lesions. BTBD7 has also been found to play an important role in cancer. High expression of BTBD7 affects tumor progression by regulating multiple pathways. Therefore, a complete understanding of BTBD7 is crucial for exploring human development and tumor progression. This paper reviews the research progress of BTBD7, which lays a foundation for the application of BTBD7 in regenerative medicine and as a biomarker for tumor prediction or potential therapeutic target.

Abstract Introduction Cordycepin has been reported to exhibit hepatic protective and anti‐inflammatory properties. Here, we investigated the role of cordycepin in ischemia/reperfusion (IR)‐induced liver injury in a mouse model. Methods Mice were pretreated with cordycepin by gavage for 3 weeks, followed by the establishment of the IR modeling. Liver injury, Suzuki's histological grading, hepatic apoptosis, and inflammatory responses were evaluated by biochemical and pathological analysis. Results It was found that Cordycepin pretreatment at 50 mg/kg for 3 weeks attenuated IR‐induced liver injury, as reflected by the significant decrease of the levels of aspartate aminotransferase, alanine transaminase, lactate dehydrogenase, and low‐density lipoprotein. Cordycepin pretreatment also reduced histopathological changes, attenuated hepatocyte apoptosis, inflammatory responses in the livers of IR mice. Mechanically, toll‐like receptor 4/nuclear factor kappa‐B signaling in liver tissues was inhibited by Cordycepin pretreatment. Conclusions In conclusion, Cordycepin pretreatment protects IR‐induced liver injury, which demonstrates its potential for the treatment of IR in the liver.

In this paper, a modified infrared and visible image registration method based on contour feature is proposed. Our method firstly extracts the feature contour and eliminates sparkling waves contour of the sea surface, determines the main direction of the contour based on the contour image, then uses the improved Scale Invariant Feature Transform (SIFT) method as the feature point to construct the descriptor, completes the registration of the two images. 30 sets of infrared and visible-band vessels images were selected for registration experiments. Compared with previous reports, the experimental results showed that the proportion of effective feature points detected by this method can reach 70%, and the average number of effective feature points detected by proposed method can reach 196 in visible band image and 279 in infrared image. The running time was 5.3599s, shortened by 25% compared with previous reports, and the average Root Mean Square Error (RMSE) value was 2.3566, smaller by 75% compared with previous reports. An effective registration method is provided, which can be used for infrared and visible image processing and comprehensive utilization of information in marine scenes.

Abstract Air supply systems are essential subsystems in proton exchange membrane (PEM) fuel cell systems. Compressors are the key devices of air supply systems that greatly influence the characteristics of fuel cells. The simulation and experimental researches on a small centrifugal compressor with high rotation speed have been presented in this paper. Firstly, the input parameters of a compressor are obtained based on the output power and operating pressure of PEM fuel cells. Then, a prototype of small centrifugal compressors applied in PEM fuel cells is designed, simulated with the computational fluid dynamics (CFD) method, and tested in actual working conditions. Finally, the simulation results show that the internal flow in compressors affects the performance strongly. The discharge pressure of the simulation is close to the test data in the studied working conditions, and the maximum error is less than 6%.

Abstract Long non‐coding RNAs (LncRNAs), which are more than 200 nucleotides in length and with limited protein‐coding potential, play vital roles in the pathogenesis, tumorigenesis, and angiogenesis of cancers. Aberrant expression of lncRNAs has been detected in various carcinomas and may be correlated with oncogenesis by affecting related genes expression. Recently, an increasing number of studies have reported on long intergenic non‐protein coding RNA 460 (LINC00460) in human tumor fields. LINC00460 is upregulated in diverse cancer tissues and cells. The upregulated expression level of LINC00460 is correlated with larger tumor size, tumor node metastasis (TNM) stage, lymph node metastasis, and shorter overall survival. The regulatory mechanism of LINC00460 was complex and diverse. LINC00460 could act as a competitive endogenous RNA (ceRNA), directly bind with proteins or regulate multiple pathways, which affected tumor progression. Moreover, LINC00460 was also identified to increase drug resistance, and therefore, weaken the effectiveness of tumor treatment. It has become increasingly important to investigate the roles of LINC00460 in various cancers by different mechanisms. Therefore, a more comprehensive understanding of LINC00460 is crucial to expound on the cellular function and molecular mechanism of human cancers. In this review, we refer to studies concerning LINC00460 and provide the basis for the evaluation of LINC00460 as a predicted biomarker or potential therapeutic target in malignancies, and also provide ideas for the future research of lncRNAs similar to LINC00460.

Abstract Transfer RNA (tRNA)-derived small RNAs (tsRNAs), a novel category of small noncoding RNAs, are enzymatically cleaved from tRNAs. Previous reports have shed some light on the roles of tsRNAs in the development of human diseases. However, our knowledge about tsRNAs is still relatively lacking. In this paper, we review the biogenesis, classification, subcellular localization as well as action mechanism of tsRNAs, and discuss the association between chemical modifications of tRNAs and the production and functions of tsRNAs. Furthermore, using immunity, metabolism, and malignancy as examples, we summarize the molecular mechanisms of tsRNAs in diseases and evaluate the potential of tsRNAs as new biomarkers and therapeutic targets. At the same time, we compile and introduce several resource databases that are currently publicly available for analyzing tsRNAs. Finally, we discuss the challenges associated with research in this field and future directions.

ObjectiveType 2 diabetes is more common in adults, but is becoming the major concern in children and adolescent recently. This study aimed to provide additional pharmaceutical management for children and adolescents with type 2 diabetes by assessing the efficacy and safety of several glucose-lowering drugs.MethodsSearches were performed in PubMed, Medline, Ovid, Cochrane Controlled Register of Trials (CENTRAL), and ClinicalTrials.gov that reported the efficacy and safety of drugs for children and adolescents with type 2 diabetes. Pooled effects were calculated by frequentist fixed effects network meta-analyses and additive network meta-analyses.ResultsA total of 12 trials assessing eight glucose-lowering drugs were included, which compose of seven trials with monotherapy and five trials with combination therapies. Network meta-analysis results showed compared to placebo, saxagliptin+metformin (mean difference (MD) -1.91% [-2.85%, -0.97%]), liraglutide+metformin (MD -1.45% [-1.65%, -1.26%]), and liraglutide (MD -0.90% [-1.35%, -0.45%]) were the top 3 drugs that significantly reduced hemoglobin A1c (HbA1c). Sitagliptin+metformin, dapagliflozin, exenatide-2mcg, linagliptin-5mg, metformin, exenatide-5/10mcg, glimepiride, and sitagliptin also showed significant reduction in HbA1c. There were no significant differences between treatments in the incidence of adverse events, except that liraglutide+metformin had significant adverse effect such as abdominal pain. In addition, dapagliflozin, sitagliptin+metformin, and saxagliptin+metformin showed better efficacy compared with FDA-approved drugs.ConclusionsThe top 10 treatments of type 2 diabetes in children and adolescents aged 10–17 years were saxagliptin+metformin, liraglutide+metformin, liraglutide, dapagliflozin, exenatide–2 mcg, sitagliptin+metformin, linagliptin–5 mg, linagliptin–1 mg, metformin, and exenatide–5/10 mcg.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=284897, identifier CRD42021284897.

Objective: Malignant ascites (MA) is a common complication of terminal cancer, which seriously affects the life quality and prognosis of patients. Both hyperthermic intraperitoneal chemotherapy (HIPEC) and traditional Chinese medicine (TCM) preparations have achieved significant efficacy in the treatment of MA. The treatment strategy of TCM combined with HIPEC has been gradually promoted and applied in China. The purpose of this systematic review and meta-analysis was to assess the efficacy of TCM combined with HIPEC in the treatment of MA.Methods: Randomized controlled trials (RCTs) of TCM combined with HIPEC for MA were searched from seven electronic databases. Two researchers used the Cochrane Collaboration’s tool to assess the risk of bias. Excel 2019 was used to establish a database for information extraction, RevMan 5.4 software was used to analyze the included test data, and STATA v16.0 was used to conduct Egger’s test to further detect publication bias.Results: A total of 19 studies involving 1,504 patients were included in this meta-analysis. The results showed that compared with the single use of HIPEC, TCM combined with HIPEC could significantly improve the clinical efficacy (RR = 1.51, 95% CI [1.40, 1.63], p < 0.00001) and karnofsky performance status (KPS) score (MD = 8.16, 95% CI [6.46, 9.85], p < 0.00001), reduce the ascites volume (MD = −156.98, 95% CI [−213.71, −100.25], p < 0.00001). However, there was no statistical significance in reducing abdominal circumference between TCM combined with HIPEC and HIPEC alone (MD = −1.8, 95% CI [−4.57, −0.97], p = 0.2).Conclusion: This study found that TCM combined with HIPEC had a beneficial therapeutic effect on MA. However, more standard, double-blind, multicenter RCTs are needed to further confirm the efficacy of TCM combined with HIPEC in the treatment of MA.Systematic Review Registration:https://www.crd.york.ac.uk/, identifier CRD42022319993.

Abstract Background This study aimed to investigate the associations of sarcopenia and its defining components with cognitive function in community-dwelling oldest old (over 80 years old) in China. Methods Sarcopenia was diagnosed by the 2019 Asian Working Group for Sarcopenia (AWGS) criteria. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). Logistic and linear regression models were used to explore the associations of sarcopenia and its defining components with risk of mild cognitive impairment (MCI), and performance on multiple cognitive domains among 428 adults aged 80 years and older. Results The overall prevalence of sarcopenia was 35.5%, with 40.34% for men and 32.14% for women. The prevalence of MCI was higher among sarcopenic oldest old than non-sarcopenic oldest old (28.95% vs. 17.39%, p = 0.005). Multivariate logistic regression analyses showed that sarcopenia [odds ratio (OR) = 1.86, 95% confidence interval (CI): 1.04–3.33], low handgrip strength (HS) [OR = 2.33, 95% CI: 1.40–3.87] and slow gait speed (GS) [OR = 2.31, 95% CI: 1.13–4.72] were significantly and independently associated with risk of MCI. Multivariate linear regression analyses showed that low HS was associated with worse performance in global cognitive function, visuospatial and executive function, naming and delayed recall. Conclusions Sarcopenia, low HS and low GS was significantly associated with MCI in community-dwelling oldest old. The associations between sarcopenia and its defining components with different cognitive subdomains could be further explored in the future.

Abstract Background The Pittsburgh Fatigability Scale (PFS) was developed to capture fatigue and demand in a single tool, filling a gap that no validated questionnaire existed to measure perceived fatigability. Since fatigability is a more sensitive measure of a person’s susceptibility to fatigue, we validated the simplified-Chinese version of the PFS among Chinese community-dwelling older adults. Methods This cross-sectional study was conducted in an urban community in Beijing between November 2018 and July 2019. The PFS was translated into simplified-Chinese by the translation, retro-translation method. Internal consistency of the Physical subscale of the PFS was evaluated by Cronbach’s alpha. Convergent validity and discriminant validity were evaluated against physical performance measures (i.e., Short Physical Performance Battery & Timed Up and Go Test) and daily living performance (i.e., Barthel Index & Instrumental activity of daily living). Results Our study included 457 participants, including 182 men (39.8%) and 275 women (60.2%). The age range of the included participants was 61–96 years (mean = 84.8 years, SD = 5.8 years). The simplified-Chinese version of PFS Physical scores showed strong internal consistency (Cronbach’s alpha = 0.81). Higher PFS Physical scores were associated with worse physical performance, and daily living performance (|correlation coefficient| range: 0.36–0.56, p

Branched-chain amino acids (BCAAs) are the three essential amino acids including leucine, isoleucine, and valine. BCAA metabolism has been linked with the development of a variety of tumors. However, the impact of dietary BCAA intake on breast tumor progression and metastasis remains to be fully explored. Here, we unexpectedly find that the elevated BCAA, either in the genetic model or via increasing dietary intake in mice, suppresses the tumor growth and lung metastasis of breast cancer. The survival analysis shows that BCAA catabolic gene expression is strongly associated with long-term oncological outcomes in patients with breast cancer. In Pp2cm knockout mice in which BCAAs accumulate due to the genetic defect of BCAA catabolism, the breast tumor growth is suppressed. Interestingly, while the cell proliferation and tumor vasculature remain unaffected, more cell death occurs in the tumor in Pp2cm knockout mice, accompanied with increased natural killer (NK) cells. Importantly, increasing BCAA dietary intake suppresses breast tumor growth in mice. On the other hand, there are fewer lung metastases from primary breast tumor in Pp2cm knockout mice and the high BCAA diet-fed mice, suggesting high BCAA also suppresses the lung metastasis of breast cancer. Furthermore, low BCAA diet promotes lung colonization of breast cancer cells in tail vein model. The migration and invasion abilities of breast cancer cells are impaired by high concentration of BCAA in culture medium. The suppressed tumor metastasis and cell migration/invasion abilities by elevated BCAA are accompanied with reduced N-cadherin expression. Together, these data show high BCAA suppresses both tumor growth and metastasis of breast cancer, demonstrating the potential benefits of increasing BCAA dietary intake in the treatment of breast cancer.

Soil phosphorus (P) can be divided into inorganic P (Pi) and organic P (Po). Microorganisms play essential roles in soil P transformation. However, there are many ways to detect P transformation, and the relationship between P forms and microorganisms under long-term fertilization is largely unclear. In this study, soil P forms were analyzed by a chemical sequential fractionation method and solution 31P nuclear magnetic resonance (31P-NMR) technique. Phospholipid fatty acid (PLFA) contents were measured by gas chromatography as the characterization of soil microbial community structures. The objective was to determine the changes of soil P forms and associated microbial community composition in mollisol with long-term fertilization. We sampled soil from a field experiment with 26-year-old continuous maize (Zea mays L.) cropping in Northeastern China. Three fertilization treatments were selected as chemical fertilization (NPK), NPK with crop straw (NPKS), and NPK with manure (NPKM). As shown in 31P-NMR spectra, orthophosphate accounted for 62.8–85.8% of total extract P. Comparison to NPK and NPKS treatments, NPKM application notably increased the concentrations of Po, Olsen-P, orthophosphate, orthophosphate monoester, and total P. Soil P fractions including resin-Pi, NaHCO3-P, NaOH-P, and HCl-P, especially Pi fractions, were enhanced by NPKM. The amounts of total PLFAs and PLFAs in bacteria, Gram-positive (G+) and Gram-negative (G−) bacteria, actinomycetes, and fungi were high in NPKM-treated soil. The percentages of PLFAs in bacteria and fungi in total soil PLFAs were 56.8% and 9.7%, respectively, which did not show any significant difference among the treatments. NPKM increased the proportions (%) of PLFAs in G+ bacteria, and NPKS increased the proportions (%) of G− bacteria in total PLFAs. The composition of soil microbial community was found to be significantly affected by soil total carbon and pH. There was a close relationship between HCl-Pi, NaHCO3-Po, orthophosphate, and pyrophosphate with anaerobe, aerobes, and G+. Manure addition directly increased soil available P concentrations, and indirectly acted through the alterations of anaerobe, aerobes, and G+. It is concluded that long-term NPKM application would lead to the accumulation of labile P and moderately labile P in mollisol through the activity of soil microbes.

High definition video application has drawn a lot of interest both from academy and industry. The relevant latest video coding technology, H.265/HEVC has been a promising area for video steganography. In this paper, we present a novel and efficient video steganography method based on transform block decision for H.265. In order to improve the visual quality of carrier video, we analyze the embedding error of data hiding with modifying partitioning parameters of CB, PB and TB, and modify the transform block decision to embed secret message and update corresponding residuals synchronously. In order to limit embedding error, we utilize an efficient embedding mapping rule which can embed N (N>1) bits message and at most modify one bit transform partitioning flag. Our experimental results show that the proposed method can achieve better visual quality, larger embedding capacity and less bit-rate increase than state-of-the-art researches.

Esophageal squamous cell carcinoma (ESCC) is the major type of EC in China. Chemoradiotherapy is a standard definitive treatment for early-stage EC and significantly improves local control and overall survival for late-stage patients. However, chemoradiotherapy resistance, which limits therapeutic efficacy and treatment-induced toxicity, is still a leading problem for treatment break. To optimize the selection of ESCC patients for chemoradiotherapy, we retrospectively analyzed the clinical features and genome landscape of a Chinese ESCC cohort of 58 patients. TP53 was the most frequent mutation gene, followed by NOTCH1. Frequently, copy number variants were found in MCL1 (24/58, 41.4%), FGF19 (23/58, 39.7%), CCND1 (22/58, 37.9%), and MYC (20/58, 34.5%). YAP1 and SOX2 amplifications were mutually exclusive in this cohort. Using univariate and multivariate analyses, the YAP1 variant and BRIP1 mutant were identified as adverse factors for OS. Patients with PI3K-Akt pathway alterations displayed longer PFS and OS than patients with an intact PI3K-Akt pathway. On the contrary, two patients with Keap1-Nrf2 pathway alterations displayed significantly shortened PFS and OS, which may be associated with dCRT resistance. Our data highlighted the prognostic value of aberrant cancer pathways in ESCC patients, which may provide guidance for better chemoradiotherapy management.

Tumor-associated macrophage (TAM) is a major component of tumor microenvironment (TME) and plays critical role in the progression of cancer metastasis. However, TAM-mediated regulation in gallbladder cancer (GBC) has not been fully characterized. Here, we found that exosomes derived from GBC cell polarized macrophage to M2 phenotype, which then facilitated the invasion and migration of GBC cells. We discovered that leptin was enriched in GBC cell-derived exosomes. Exosomal leptin levels promoted invasion and migration of GBC-SD cells. The inhibition of leptin not only attenuated M2 macrophage of polarization but also inhibited the invasive and migratory ability of GBC cell. In addition, GBC-SD cell-derived exosomal leptin induced M2 polarization of macrophage via activation of STAT3 signal pathway. Taken together, our results suggested that GBC cells secrete exosome-enclosed leptin facilitated cell invasion and migration via polarizing TAM.

Objectives The prevalence of childhood hypertension is rising in parallel with the increasing prevalence of overweight and obesity in children. How growth trajectories from childhood to puberty relate to high blood pressure (HBP) is not well defined. We aimed to characterise potential body mass index (BMI) dynamic changing trajectories from childhood to puberty and investigate their association with HBP.Design A dynamic prospective cohort.Setting China Health and Nutrition Survey 1991–2015.Participants There were 1907 participants (1027 men and 880 women) in this study.Outcomes The primary outcome was HBP defined as systolic blood pressure (SBP)/diastolic blood pressure (DBP) exceeding the standards or diagnosis by medical records or taking antihypertensive medication.Results A model of cubic parameters with three groups was chosen, labelled as normal increasing group (85.16%, n=1624), high increasing group (9.81%, n=187) and resolving group (5.03%, n=96). Compared with the normal increasing group, the unadjusted HRs (95% CIs) for the resolving and high increasing groups were 0.91 (0.45 to 1.86) and 1.88 (1.26 to 2.81), respectively. After adjusting for baseline age, region, sex, baseline BMI z-score, baseline SBP and baseline DBP in model 3, the HRs (95% CIs) for the resolving and high increasing groups were 0.66 (0.30 to 1.45) and 1.56 (1.02 to 2.38).Conclusions These results indicate that the BMI trajectories from childhood to puberty have significant impact on HBP risk. Puberty is a crucial period for the development of HBP.

Perivascular adipose tissue (PVAT) is the connective tissue around most blood vessels throughout the body. It provides mechanical support and maintains vascular homeostasis in a paracrine/endocrine manner. Under physiological conditions, PVAT has anti-inflammatory effects, improves free fatty acid metabolism, and regulates vasodilation. In pathological conditions, PVAT is dysfunctional, secretes many anti-vasodilator factors, and participates in vascular inflammation through various cells and mediators; thus, it causes dysfunction involving vascular smooth muscle cells and endothelial cells. Inflammation is an important pathophysiological event in many vascular diseases, such as vascular aging, atherosclerosis, and hypertension. Therefore, the pro-inflammatory crosstalk between PVAT and blood vessels may comprise a novel therapeutic target for the prevention and treatment of vascular diseases. In this review, we summarize findings concerning PVAT function and inflammation in different pathophysiological backgrounds, focusing on the secretory functions of PVAT and the crosstalk between PVAT and vascular inflammation in terms of vascular aging, atherosclerosis, hypertension, diabetes mellitus, and other diseases. We also discuss anti-inflammatory treatment for potential vascular diseases involving PVAT.

In this paper, the mineralogical composition, concentrations, distribution, and modes of occurrence of the trace elements in coal from the Anjialing coal seam 9 in the Pingshuo mining district, Ningwu coalfield, were studied using optical microscopy, X-ray powder diffraction (XRD), inductively coupled plasma optical emission spectrometry (ICP-OES), inductively coupled plasma mass spectrometry (ICP-MS), and sequential chemical extraction procedures (SCEPs). The identified minerals included mainly kaolinite, boehmite, pyrite, calcite, quartz, and muscovite. Compared to other hard coal from around the world, the coal from seam 9 was enriched with lithium (Li); slightly enriched with gallium (Ga), hafnium (Hf), zirconium (Zr), and mercury (Hg); typically enriched with lead (Pb), and depleted in arsenic (As). The results of the SCEPs analysis showed that Li, Ga, Zr, and Hf were mainly associated with clay minerals. Arsenic mainly occurred in its silicate and sulfide forms in pyrite and Pb was mainly associated with aluminosilicate, sulfide, and carbonate minerals.

BackgroundImmunotherapy, adjuvant chemotherapy, and prognosis of colorectal cancer are associated with MSI. Biopsy pathology cannot fully reflect the MSI status and heterogeneity of rectal cancer.PurposeTo develop a radiomic-based model to preoperatively predict MSI status in rectal cancer on MRI.AssessmentThe patients were divided into two cohorts (training and testing) at a 7:3 ratio. Radiomics features, including intensity, texture, and shape, were extracted from the segmented volumes of interest based on T2-weighted and ADC imaging.Statistical TestsIndependent sample t test, Mann-Whitney test, the chi-squared test, Receiver operating characteristic curves, calibration curves, decision curve analysis and multi-variate logistic regression analysisResultsThe radiomics models were significantly associated with MSI status. The T2-based model showed an area under the curve of 0.870 with 95% CI: 0.794–0.945 (accuracy, 0.845; specificity, 0.714; sensitivity, 0.976) in training set and 0.895 with 95% CI, 0.777–1.000 (accuracy, 0.778; specificity, 0.887; sensitivity, 0.772) in testing set. The ADC-based model had an AUC of 0.790 with 95% CI: 0.794–0.945 (accuracy, 0.774; specificity, 0.714; sensitivity, 0.976) in training set and 0.796 with 95% CI, 0.777–1.000 (accuracy, 0.778; specificity, 0.889; sensitivity, 0.772) in testing set. The combined model integrating T2 and ADC features showed an AUC of 0.908 with 95% CI: 0.845–0.971 (accuracy, 0.857; specificity, 0.762; sensitivity, 0.952) in training set and 0.926 with 95% CI: 0.813-1.000 (accuracy, 0.852; specificity, 1.000; sensitivity, 0.778) in testing set. Calibration curve showed that the combined score had a good calibration degree, and the decision curve demonstrated that the combined score was of benefit for clinical use.Data ConclusionRadiomics analysis of T2W and ADC images showed significant relevance in the prediction of microsatellite status, and the accuracy of combined model of ADC and T2W features was better than either alone.

Physiological reactive oxygen species (ROS) are important regulators of intercellular signal transduction. Oxidative and antioxidation systems maintain a dynamic balance under physiological conditions. Increases in ROS levels destroy the dynamic balance, leading to oxidative stress damage. Oxidative stress is involved in the pathogenesis of aging-related cardiovascular diseases (ACVD), such as atherosclerosis, myocardial infarction, and heart failure, by contributing to apoptosis, hypertrophy, and fibrosis. Oxidative phosphorylation in mitochondria is the main source of ROS. Increasing evidence demonstrates the relationship between ACVD and humanin (HN), an endogenous peptide encoded by mitochondrial DNA. HN protects cardiomyocytes, endothelial cells, and fibroblasts from oxidative stress, highlighting its protective role in atherosclerosis, ischemia–reperfusion injury, and heart failure. Herein, we reviewed the signaling pathways associated with the HN effects on redox signals, including Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2), chaperone-mediated autophagy (CMA), c-jun NH2 terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38 MAPK), adenosine monophosphate-activated protein kinase (AMPK), and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)-Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3). Furthermore, we discussed the relationship among HN, redox signaling pathways, and ACVD. Finally, we propose that HN may be a candidate drug for ACVD.

Objective The aim of this study was to investigate the underlying mechanism whereby HBx modulates the targeting of NUSAP1 by miR-18b to enhance hepatocarcinogenesis.Methods We employed an integrated approach of bioinformatics analysis and molecular experiments in hepatoma cells, HBV transgenic mice, and clinical liver cancer tissues to investigate the role of HBx-regulated miR-18b in the development of liver cancer.Results In this study, we report that the HBx-mediated tumor suppressor miR-18b modulates hepatocarcinogenesis during the host-HBV interaction. The expression levels of miR-18b were lower in clinical HBV-positive liver cancer tissues and liver tissues of HBV-transgenic mice. Interestingly, HBx inhibited miR-18b expression by inducing the methylation of CpG islands in its promoter. Accordingly, we tested the hypothesis that HBx enhanced hepatocarcinogenesis by increasing the expression of target genes of miR-18b. Moreover, we identified nucleolar spindle-associated protein 1 (NUSAP1) as one of the target genes of miR-18b. NUSAP1 was expressed at high levels in liver cancer tissues. Interestingly, HBx up-regulated NUSAP1 by suppressing miR-18b. Functionally, miR-18b significantly inhibited the proliferation of hepatoma cells by depressing NUSAP1 levels in vivo and in vitro.Conclusions Thus, we conclude that the targeting of NUSAP1 mRNA by the tumor suppressor miR-18b is controlled by HBx-modulated promoter methylation during the host-virus interaction, leading to hepatocarcinogenesis. Our findings provide new insights into the mechanism by which HBx-mediated miRNAs modulate hepatocarcinogenesis.

Abstract Background Few studies have investigated the associations between outdoor air pollution and outpatient visits for respiratory diseases (RDs) in general population. Methods We collected daily outpatient data of primary RDs from five hospitals in Jinan during January 2012 and December 2016, as well as daily measurements of air pollutants from the Jinan Environmental Monitoring Center and daily meteorological variables from the China Meteorological Data Sharing Service System. A generalized additive model (GAM) with quasi-Poisson regression was constructed to estimate the associations between daily average concentrations of outdoor air pollutants (PM2.5,PM10, SO2, NO2, CO and O3) and daily outpatient visits of RDs after adjusting for long-time trends, seasonality, the “day of the week” effect, and weather conditions. Subgroup analysis stratified by gender, age group and the type of RDs was conducted. Results A total of 1,373,658 outpatient visits for RDs were identified. Increases of 10 μg/m3 in PM2.5, PM10, NO2, CO and O3 were associated with0.168% (95% CI, 0.072–0.265%), 0.149% (95% CI, 0.082–0.215%), 0.527% (95% CI, 0.211–0.843%), 0.013% (95% CI, 0.003–0.023%), and 0.189% (95% CI, 0.032–0.347%) increases in daily outpatient visits for RDs, respectively. PM2.5 and PM10 showed instant and continuous effects, while NO2, CO and O3 showed delayed effects on outpatient visits for RDs. In stratification analysis, PM2.5 and PM10 were associated with acute RDs only. Conclusions Exposure to outdoor air pollutants including PM2.5, PM10, NO2, CO and O3 associated with increased risk of outpatient visits for RDs.

The power system using carbon dioxide (CO2) as the working fluid has been the research hotspot due to its high performance and potential for use in many energy fields. In this paper, the difference of compression processes between supercritical CO2 (S–CO2) and transcritical CO2 (T-CO2) power cycles is researched, and their effects on the thermodynamic performances of power cycles and equipment are discussed. The results show that the thermal efficiency and net output power increase with the decreasing of the compressor/pump inlet temperature, and there is a big jump near the critical temperature. The condensation margin is more sensitive to the temperature than the pressure near the critical point. To minimize the compressor input power and to guarantee the reliability of equipment, the inlet parameters of compressors should be designed and operated carefully. And the inlet velocity of compressors should be set below the usually recommend value.

Gastric cancer (GC) is the most common malignancy of the stomach. This study was aimed at elucidating the regulatory network of circRNA-miRNA-mRNA and identifying the precise inflammation-related targets in GC. The expression profiles of GSE83521, GSE78091, and GSE33651 were obtained from the GEO database. Interactions between miRNAs and circRNAs were investigated by the Circular RNA Interactome, and targets of miRNAs were predicted with miRTarBase. Then, a circRNA/miRNA/mRNA regulatory network was constructed. Also, functional enrichment analysis of selected differentially expressed genes (DEGs) was performed. The inflammation-/GC-related targets were collected in the GeneCards and GenLiP3 database, respectively. And a protein-protein interaction (PPI) network of DE mRNAs was constructed with STRING and Cytoscape to identify hub genes. The genetic alterations, neighboring gene networks, expression levels, and the poor prognosis of hub genes were investigated in cBioPortal, Oncomine, and Human Protein Atlas databases and Kaplan-Meier plotter, respectively. A total of 10 DE miRNAs and 33 DEGs were identified. The regulatory network contained 26 circRNAs, 10 miRNAs, and 1459 mRNAs. Functional enrichment analysis revealed that the selected 33 DEGs were involved in negative regulation of fat cell differentiation, response to wounding, extracellular matrix- (ECM-) receptor interaction, and regulation of cell growth pathways. THBS1, FN1, CALM1, COL4A1, CTGF, and IGFBP5 were selected as inflammation-related hub genes of GC in the PPI network. The genetic alterations in these hub genes were related to amplification and missense mutations. Furthermore, the genes RYR2, ERBB2, PI3KCA, and HELZ2 were connected to hub genes in this study. The hub gene levels in clinical specimens were markedly upregulated in GC tissues and correlated with poor overall survival (OS). Our results suggest that THBS1, FN1, CALM1, COL4A1, CTGF, and IGFBP5 were associated with the pathogenesis of gastric carcinogenesis and may serve as biomarkers and inflammation-related targets for GC.

Summary: In addition to acting as building blocks for biosynthesis, amino acids might serve as signaling regulators in various physiological and pathological processes. However, it remains unknown whether amino acid levels affect the activities of hematopoietic stem cells (HSCs). By using a genetically encoded fluorescent sensor of the intracellular levels of branched-chain amino acids (BCAAs), we could monitor the dynamics of BCAA metabolism in HSCs. A mitochondrial-targeted 2C-type Ser/Thr protein phosphatase (PPM1K) promotes the catabolism of BCAAs to maintain MEIS1 and p21 levels by decreasing the ubiquitination-mediated degradation controlled by the E3 ubiquitin ligase CDC20. PPM1K deficiency led to a notable decrease in MEIS1/p21 signaling to reduce the glycolysis and quiescence of HSCs, followed by a severe impairment in repopulation activities. Moreover, the deletion of Ppm1k dramatically extended survival in a murine leukemia model. These findings will enhance the current understanding of nutrient signaling in metabolism and function of stem cells. : Liu et al. show that the dynamics of BCAA metabolism in hematopoietic stem cells (HSCs) and leukemia-initiating cells (LICs) can be monitored by a genetically encoded fluorescent sensor. PPM1K promotes BCAA catabolism and maintains the glycolysis and quiescence of HSCs/LICs through the downregulation of CDC20-mediated ubiquitination of MEIS1 and p21. Keywords: branched-chain amino acids, PPM1K, ubiquitination, CDC20, MEIS1/p21, hematopoietic stem cells, leukemia-initiating cells

This paper presents a novel and robust data hiding method based on H.265/High Efficiency Video Coding (HEVC) standard. To improve the robustness of data hiding, the embedded data are first encoded into the encoded data by using the BCH syndrome code (BCH code) technique. To improve the visual quality of data hiding, three groups of the prediction directions are provided to limit the intra-frame distortion drift. Then, the encoded data are embedded into the multi-coefficients of the selected 4 × 4 luminance discrete sine transform blocks, which meet the groups. It is experimentally proven that the proposed method can achieve greater robustness, better visual quality, and higher embedding capacity than previously studied methods.

The ocean connects all continents and is an important space for human activities. Ship detection with electro-optical images has shown great potential due to the abundant imaging spectrum and, hence, strongly supports human activities in the ocean. A suitable imaging spectrum can obtain effective images in complex marine environments, which is the premise of ship detection. This paper provides an overview of ship detection methods with electro-optical images in marine environments. Ship detection methods with sea–sky backgrounds include traditional and deep learning methods. Traditional ship detection methods comprise the following steps: preprocessing, sea–sky line (SSL) detection, region of interest (ROI) extraction, and identification. The use of deep learning is promising in ship detection; however, it requires a large amount of labeled data to build a robust model, and its targeted optimization for ship detection in marine environments is not sufficient.

In the field of industrial wastewater treatment, membrane separation technology, as an emerging separation technology, compared with traditional separation technology such as precipitation, adsorption, and ion exchange, has advantages in separation efficiency, low energy consumption, low cost, simple operation, and no secondary pollution. The application has been expanding in recent years, but membrane fouling and other problems have seriously restricted the development of membrane technology. Natural cellulose is one of the most abundant resources in nature. In addition, nanocellulose has characteristics of high strength and specific surface area, surface activity groups, as well as being pollution-free and renewable, giving it a very wide development prospect in many fields, including membrane separation technology. This paper reviews the current status of nanocellulose filtration membrane, combs the widespread types of nanocellulose and its derivatives, and summarizes the current application of cellulose in membrane separation. In addition, for the purpose of nanocellulose filtration membrane in wastewater treatment, nanocellulose membranes are divided into two categories according to the role in filtration membrane: the application of nanocellulose as membrane matrix material and as a modified additive in composite membrane in wastewater treatment. Finally, the advantages and disadvantages of inorganic ceramic filtrations and nanocellulose filtrations are compared, and the application trend of nanocellulose in the filtration membrane direction is summarized and discussed.

Source camera identification has long been a hot topic in the field of image forensics. Besides conventional feature engineering algorithms developed based on studying the traces left upon shooting, several deep-learning-based methods have also emerged recently. However, identification performance is susceptible to image content and is far from satisfactory for small image patches in real demanding applications. In this paper, an efficient patch-level source camera identification method is proposed based on a convolutional neural network. First, in order to obtain improved robustness with reduced training cost, representative patches are selected according to multiple criteria for enhanced diversity in training data. Second, a fine-grained multiscale deep residual prediction module is proposed to reduce the impact of scene content. Finally, a modified VGG network is proposed for source camera identification at brand, model, and instance levels. A more critical patch-level evaluation protocol is also proposed for fair performance comparison. Abundant experimental results show that the proposed method achieves better results as compared with the state-of-the-art algorithms.

Buthus martensii Karsch (BmK), is a kind of traditional Chinese medicine, which has been used for a long history for the treatment of many diseases, such as inflammation, pain and cancer. In this study, DKK-SP1/2/3 genes were screened and extracted from the cDNA library of BmK. The DKK-SP1/2/3 were expressed by using plasmid pSYPU-1b in E. coli BL21, and recombinant proteins were obtained by column chromatography. In the xylene-induced mouse ear swelling and carrageenan-induced rat paw swelling model, DKK-SP1 exerted a significant anti-inflammatory effect by inhibiting the expression of Nav1.8 channel. Meanwhile, the release of pro-inflammatory cytokines (COX-2, IL-6) was decreased significantly and the release of anti-inflammatory cytokines (IL-10) were elevated significantly. Moreover, DKK-SP1 could significantly decrease the Nav1.8 current in acutely isolated rat DRG neurons. In the acetic acid-writhing and ION-CCI model, DKK-SP2 displayed significant analgesic activity by inhibiting the expression of the Nav1.7 channel. Moreover, DKK-SP2 could significantly inhibit the Nav1.7 current in the hNav1.7-CHO cells.

The stimulator of interferon genes (STING) protein has been shown to play a pivotal role in response to both cytosolic RNA and dsDNA to elicit interferon (IFN) production in mammals. However, the role of duck STING (DuSTING) in antiviral innate immunity, especially in anti-RNA virus infection, has yet to be elucidated. In this study, the function of DuSTING in IFN induction and its role in anti-RNA virus infections were studied. DuSTING was amplified via reverse transcription-polymerase chain reaction (RT-PCR) from Pekin duck, showing that its cDNA sequence contains an open reading frame (ORF) of 1,149 bp and encodes 382 amino acids (aa). Sequence alignment showed that DuSTING protein shares 71.1, 43.4, and 33.3% identity with chickens, humans, and zebra fish, respectively. Overexpression of DuSTING in duck embryo fibroblasts (DEFs) strongly activated IFN-β promotor activity. Deletion mutant analysis revealed that the first 42 aa containing the first transmembrane (TM) domains and the last 32 aa containing a part of the C-terminal tail (CTT) are essential for its IFN-β activation. In vitro experiments showed that the mRNA levels of DuSTING and IFNs were all upregulated when the DEFs were infected with H9N2 avian influenza virus (AIV) SH010, while overexpression of DuSTING inhibited the replication of this virus. In vivo studies showed that DuSTING mRNA was widely expressed in different tissues, and was up-regulated in the spleen and lung of ducks challenged with SH010. In conclusion, our results indicate that DuSTING is an essential IFN mediator and plays a role in anti-RNA virus innate immunity.

Recent studies show branched-chain amino acid (BCAA) catabolic pathway is defective in obese animals and humans, contributing to the pathogenesis of insulin resistance and diabetes. However, in the context of obesity, various processes including the dysfunctional lipid metabolism can affect insulin sensitivity and glycemic regulation. It remains unclear how BCAA catabolic defect may exert direct impacts on glucose metabolism without the disturbance of obesity. The current study characterized the glucose metabolism in lean mice in which the genetic deletion of PP2Cm leads to moderate BCAA catabolic defect. Interestingly, compared to the wildtype control, lean PP2Cm deficient mice showed enhanced insulin sensitivity and glucose tolerance, lower body weight, and the preference for carbohydrate over lipids utilization. Metabolomics profiling of plasma and tissues revealed significantly different metabolic patterns in the PP2Cm deficient mice, featured by the marked alterations in glucose metabolic processes, including gluconeogenesis/glycolysis, glycogen metabolism, and tricarboxylic acid cycle. The metabolic changes of glucose were predominantly observed in liver but not skeletal muscle or white adipose tissue. The elevated branched-chain keto acids (BCKAs) resulted from the BCAA catabolic defect may play a critical role in regulating the expression of key regulators of glucose metabolic processes and the activity of respiratory Complex II/succinate dehydrogenase in TCA cycle. Together, these results show BCAA catabolic defect significantly alters glucose metabolism in lean mice with some impacts different or even opposite from those in obese mice, highlighting the critical role of BCAA catabolism in glycemic regulation and the complex interplay between macronutrients in lean and obese animals.

TANK-binding kinase 1 (TBK1) is involved in innate immunity, prompting transcriptional induction of type I interferons in response to pathogenic infection. Many studies have focused on mammals but the function of TBK1 in chickens remains poorly defined. CRISPR/Cas9 system has made gene-knockout easy to accomplish. Although CRISPR/Cas9 has been used in chicken cells, low mutation efficiency limits its wide application in chickens. In this study, an effective gene-knockout system was developed based on the CRISPR/Cas9 system in chicken embryonic fibroblast DF-1. Two CRISPR/Cas9 plasmids were constructed, TBK1-g1 and TBK1-g2, which express gRNAs targeting different sequences of the chicken TBK1 gene. After transfection and enrichment with puromycin screening, the mutation rates as assessed via T7E1 assay were 88.05 and 89.55%, respectively, and subsequent sequence analysis showed mutation efficiencies of 86.67 and 93.33%. With the limiting-dilution method, a chTBK1 gene-deficiency monoclonal cell line was obtained and was named DF-1-TBK1-C3. The DF-1-TBK1-C3 cells exhibited normal morphology and maintained stable proliferation ability compared to wild-type cells. The gene-overexpression system and luciferase reporter assay showed that IFN-β induction induced by chSTING was almost completely blocked in DF-1-TBK1-C3 cells. With quantitative real-time PCR, we further confirmed the essential role of chTBK1 in the chSTING-mediated IFN-β induction. At last, the study demonstrated that the chTBK1 knockout system is also applicable in primary chick embryo fibroblasts (CEFs). In this study, an effective gene-knockout system was applied in chickens, a TBK1 gene-deleted DF-1 cell line was successfully created using this system, and with the chTBK1 knockout cells, chTBK1 was revealed to be indispensable in STING-mediated IFN-β activation in chicken cells.

Objectives: The aim of this study was to quantify the relationship between meteorological factors and the occurrence of hand, foot, and mouth disease (HFMD) among children in Shandong Province, China, at a county level, using spatial panel data models. Methods: Descriptive analysis was applied to describe the epidemic characteristics of HFMD from January 2008 to December 2012, and then a global autocorrelation statistic (Moran's I) was used to detect the spatial autocorrelation of HFMD in each year. Finally, spatial panel data models were performed to explore the association between the incidence of HFMD and meteorological factors. Results: Moran's I at the county level were high, from 0.30 to 0.45 (p