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Abstract Background Patients with non‐small cell lung cancer (NSCLC) with liver metastasis have a poor prognosis, and there are no reliable biomarkers for predicting disease progression. Currently, no recognized and reliable prediction model exists to anticipate liver metastasis in NSCLC, nor have the risk factors influencing its onset time been thoroughly explored. Methods This study conducted a retrospective analysis of 434 NSCLC patients from two hospitals to assess the association between the risk and timing of liver metastasis, as well as several variables. Results The patients were divided into two groups: those without liver metastasis and those with liver metastasis. We constructed a nomogram model for predicting liver metastasis in NSCLC, incorporating elements such as T stage, N stage, M stage, lack of past radical lung cancer surgery, and programmed death ligand 1 (PD‐L1) levels. Furthermore, NSCLC patients with wild‐type EGFR, no prior therapy with tyrosine kinase inhibitors (TKIs), and no prior radical lung cancer surgery showed an elevated risk of early liver metastasis. Conclusion In conclusion, the nomogram model developed in this study has the potential to become a simple, intuitive, and customizable clinical tool for assessing the risk of liver metastasis in NSCLC patients following validation. Furthermore, it provides a framework for investigating the timing of metachronous liver metastasis.

Abstract Background While de novo cholesterol biosynthesis plays a crucial role in chemotherapy resistance of colorectal cancer (CRC), the underlying molecular mechanism remains poorly understood. Methods We conducted cell proliferation assays on CRC cells with or without depletion of squalene epoxidase (SQLE), with or without 5-fluorouracil (5-FU) treatment. Additionally, a xenograft mouse model was utilized to explore the impact of SQLE on the chemosensitivity of CRC to 5-FU. RNA-sequencing analysis and immunoblotting analysis were performed to clarify the mechanism. We further explore the effect of SQLE depletion on the ubiquitin of NF-κB inhibitor alpha (IκBα) and (S)-2,3-epoxysqualene on the binding of IκBα to beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) by using immunoprecipitation assay. In addition, a cohort of 272 CRC patients were selected for our clinical analyses. Results Mechanistically, (S)-2,3-epoxysqualene promotes IκBα degradation and subsequent NF-κB activation by enhancing the interaction between BTRC and IκBα. Activated NF-κB upregulates the expression of baculoviral IAP repeat containing 3 (BIRC3), sustains tumor cell survival after 5-FU treatment and promotes 5-FU resistance of CRC in vivo. Notably, the treatment of terbinafine, an inhibitor of SQLE commonly used as antifungal drug in clinic, enhances the sensitivity of CRC to 5-FU in vivo. Additionally, the expression of SQLE is associated with the prognosis of human CRC patients with 5-FU-based chemotherapy. Conclusions Thus, our finding not only demonstrates a new role of SQLE in chemoresistance of CRC, but also reveals a novel mechanism of (S)-2,3-epoxysqualene-dependent NF-κB activation, implicating the combined potential of terbinafine for 5-FU-based CRC treatment.

Abstract Road extraction from remote-sensing images is of great significance for vehicle navigation and emergency insurance. However, the road information extracted in the remote-sensing image is discontinuous because the road in the image is often obscured by the shadows of trees or buildings. Moreover, due to the scale difference of roads in remote-sensing images, it remains a computational challenge to extract small-size roads from remote-sensing images. To address those problems, we propose a road extraction method based on adaptive global feature fusion (AGF-Net). First, a dilated convolution strip attention (DCSA) module is designed from the encoder–decoder structure. It consists of the dilated convolution and the strip attention module, which adaptively emphasizes relevant features in vertical and horizontal directions. Then, multiple global feature fusion modules (GFFM) in the skip connection are designed to supplement the decoder with road detail features, and we design a multi-scale strip convolution module (MSCM) to implement the GFFM module to obtain multi-scale road information. We compare AGF-Net to state-of-the-art methods and report their performance using standard evaluation metrics, including Intersection over Union (IoU), F1-score, precision, and recall. Our proposed AGF-Net achieves higher accuracy compared to other existing methods on the Massachusetts Road Dataset, DeepGlobe Road Dataset, CHN6-CUG Road Dataset, and BJRoad Dataset. The IoU obtained on these datasets are 0.679, 0.673, 0.567, and 0.637, respectively.

BackgroundLong-term exposure to ambient fine particulate matter (PM2.5) may increase the risk of diabetes, and a healthy diet can effectively control fasting blood glucose levels. However, it is unclear whether dietary factors have a moderating effect on the risk of diabetes associated with atmospheric PM2.5 exposure. ObjectiveTo investigate the association between long-term exposure to PM2.5 and diabetes in rural areas of Ningxia, and potential interaction of long-term exposure to atmospheric PM2.5 and diet on diabetes.MethodsThe study subjects were selected from the baseline survey data of the China Northwest Cohort-Ningxia (CNC-NX) , a natural population cohort. A total of 13917 subjects were included, excluding participants with missing covariate information. We utilized the annual average ambient PM2.5 concentration from 2014 to 2018 as the long-term exposure level. Logistic regression and multiple linear regression were employed to analyze the associations of long-term atmospheric PM2.5 exposure with diabetes and fasting blood glucose levels. Stratification by frequency of vegetable consumption, frequency of fruit consumption, and salty taste was used to examine moderating effects on the diabetes risk associated with atmospheric PM2.5 exposure.ResultsThe mean age of the 13917 subjects was (56.8±10.0) years, and the prevalence of diabetes was 9.8%. Between 2014 and 2018, the average annual concentration of PM2.5 was (38.10±4.67) μg·m−3. The risk (OR) of diabetes was 1.018 (95%CI: 1.005, 1.032) and the fasting blood glucose was increased by 0.011 (95%CI: 0.004, 0.017) mmol·L−1 for each 1 μg·m−3 increase in PM2.5 concentration. Compared to those who consumed vegetables < 1 time per week, individuals who consume vegetables 1-3 times per week and ≥4 times per week had a reduced risk of developing diabetes by 27.1% (OR=0.729, 95%CI: 0.594, 0.893) and 16.8% (OR=0.832, 95%CI: 0.715, 0.971) respectively. Similarly, when compared to those who consumed fruits

Building extraction from remote sensing images (RSIs) requires exploring multiscale boundary detailed information and extracting it completely, which is challenging but indispensable. However, existing solutions tend to augment feature information solely through multiscale fusion and apply attention mechanisms to focus on feature relationships within a single layer while ignoring the multiscale information, which affects segmentation results. Therefore, enhancing the capability of the network to adaptively capture multiscale information and capture the global relationship of features remains a pivotal challenge in overcoming the aforementioned hurdles. To address the preceding challenge, we propose a Multiscale Direction Context-aware network with Global Attention (MDCGA-Net), employing a classic encoder–decoder architecture enhanced with direction information and global attention flow. Specifically, in the encoder part, the multiscale layer is used to extract contextual information from the interlayer. In addition, the multiscale direction context-aware module is adopted to adaptively acquire multiscale information. In the decoder part, we propose a global attention gate module to capture discriminative features. Furthermore, we construct an operation of attention feature flow to obtain the global relationship among the different features with long-range dependencies, which guarantees the integrity of results. Finally, we have performed comprehensive experiments on three public datasets to showcase the efficacy and efficiency of MDCGA-Net in building extraction.

BackgroundThe impact of atmospheric fine particulate matter (PM2.5) and ozone (O3) on the mortality of circulatory system diseases cannot be ignored. However, whether the interaction between PM2.5 and O3 can affect population health is rarely reported and requires study. ObjectiveTo investigate the individual and interactive impacts of atmospheric PM2.5 and O3 on the mortality of circulatory system diseases in the population of Ningxia region. MethodsThe data of 119647 deaths due to circulatory system diseases, daily average concentrations of atmospheric pollutants, and meteorological data in Ningxia from 2013 to 2020 were retrieved. PM2.5 was divided into low, medium, and high concentrations according to the primary and secondary national limits (35 and 75 μg·m−3) of the Ambient air quality standards. Similarly, O3 was divided into low, medium, and high concentrations according to the national limits (100 and 160 μg·m−3). Using a generalized additive mixed model based on quasi Poisson distribution, the impacts of atmospheric PM2.5 and O3 as well as their interaction on the mortality of circulatory system diseases were analyzed using the population data of Ningxia region. ResultsDuring the target period, males and the ≥ 65 year group accounted for larger proportions of deaths due to circulatory system diseases (55.47% and 79.87% respectively). The daily average concentration of PM2.5 (40.25 μg·m−3) exceeded the national primary limit. In the single pollution model, the highest cumulative lag effects for mortality from circulatory system diseases were PM2.5 exposure over previous 1 d (lag01) and O3 exposure for previous 2 d (lag02), and their excess risk (ER) values were 1.03% (95%CI: 0.67%, 1.40%) and 1.02% (95%CI: 0.57%, 1.50%), respectively. The results of concentration stratification analysis showed that the most significant risks of death from circulatory system diseases [ER (95%CI): 1.12% (0.32%, 1.92%) and 0.95% (0.13%, 1.79%) respectively] were found at medium PM2.5 and O3 concentrations. The interaction analysis revealed that under, a synergistic effect on the risk of death from circulatory system diseases was identified (relative excess risk due to interaction=3.08%, attributable proportion of interaction=2.90%, synergy index=1.89) when considering the coexistence of PM2.5 and O3 above the primary limit. As the concentrations of PM2.5 and O3 increased, the synergistic effect increased the risk of death from circulatory system diseases in the general population, men, women, and the ≥ 65 years group. ConclusionBoth atmospheric PM2.5 and O3 can increase the risk of death from circulatory system diseases, and the two pollutants have a synergistic effect on the risk of death from circulatory system diseases.

Summary: Loss of Protocadherin 9 (PCDH9) is associated with the metastasis and the prognosis of gastric cancer patients, while the molecular mechanism of PCDH9-impaired gastric cancer metastasis remains unclear. Here we show that PCDH9 is cleaved in gastric cancer cells. Intracellular domain of PCDH9 translocates into nucleus, where it interacts with DNA methyltransferase 1 (DNMT1) and increases DNMT1 activity. Activated DNMT1 downregulates cadherin 2 (CDH2) expression by increasing DNA methylation at its promoter, thereby dampening the migration and in vivo metastasis of gastric cancer cells. In addition, the levels of nuclear PCDH9 correlate with CDH2 expression, lymph node metastasis, and the prognosis of gastric cancer patients. Our finding demonstrates a unique mechanism of nuclear PCDH9-impaired gastric cancer metastasis by promoting DNA methylation of CDH2 promoter.

Abstract Background The main symptoms of preeclampsia (PE), a specific ailment that develops during pregnancy, are proteinuria and hypertension. The pathological root of the onset and progression of PE is widely regarded as abnormal placental trophoblast cell function. This study aimed to look into the character and mechanism of Placenta-specific 8 (PLAC8) in trophoblast cell invasion and migration. Methods Expressions of PLAC8 and AlkB homologue 5 (ALKBH5) were examined by western blot and quantitative real-time PCR. The m6A level of PLAC8 mRNA was detected by methylated RNA Immunoprecipitation. Using Transwell experiments, cell invasion and migration were examined. The enzyme-linked immunosorbent assay was utilized to analyze the MMP-2 and MMP-9 secretion levels. RNA pull-down and RNA immunoprecipitation were conducted to detect the binding between ALKBH5 and PLAC8. Results In PE tissue and hypoxia-treated HTR-8/SVneo cells, levels of ALKBH5 and PLAC8 were increased, and PLAC8 m6A methylation levels were decreased. There was a positive correlation between PLAC8 and ALKBH5 expression in clinical tissues. In addition, overexpressing PLAC8 promoted HTR-8/SVneo cell migration and invasion, and so as the levels of MMP-2 and MMP-9; while interference with PLAC8 reduced the migration and invasion of hypoxia-treated HTR-8/SVneo cells, and so as the levels of MMP-2 and MMP-9. Moreover, the PLAC8 mRNA’s m6A modification site was GAACU (Position 1449, Site 2). Increased levels of MMP-2 and MMP-9, as well as migration and invasion of HTR-8/SVneo cells exposed to hypoxia, were all facilitated by the m6A Site2 mutation. Furthermore, ALKBH5 could bind to PLAC8, reduce its m6A modification, and promote its expression. Conclusion High-expressed ALKBH5 inhibits the m6A level of PLAC8 mRNA and promotes PLAC8 expression, while PLAC8 overexpression can promote hypoxia-induced invasion and migration of HTR-8/Svneo cells, indicating its potential protective function in PE.

Abstract Background Patients with stroke frequently experience walking dysfunction. Core training can help improve balance and walking function in patients with stroke. However, core training movements in clinical practice are numerous and differently targeted. Therefore, this study will investigate the improvement of walking function in patients with combined diaphragmatic breathing maneuver (DBM) and draw-in breathing technique (ADIM) training. Methods This single-blind, randomized controlled preliminary will analyze the viability of DBM combined ADIM training versus routine rehabilitation therapy in patients with stroke with early to mid-stroke. Patients will be randomly assigned to either the DBM and ADIM training or the routine rehabilitation training. We will recruit 42 stroke inpatients from the Second Rehabilitation Hospital of Shanghai who meet the trial criteria and measure the balance and walking functions and improvement of that after 4 weeks of intervention. The primary outcome is the 10 m maximum walking test (10MWT). The secondary outcomes indices include the limits of stability test (LOS), Berg balance scale test (BBS), Functional Ambulation Categories test (FAC), Timed Up and Go test (TUG), trunk impairment scale test (TIS), ultrasound indicators of the diaphragm and transversus abdominis (UI), rhythmic weight shift test (RWS), walk across test (WA), Fugl-Meyer assessment of lower extremity (FMA-LE), and Barthel index of ADL test. Discussion The primary objective of this project was to investigate the effects of DBM combined with ADIM on balance capacity and walking function for patients with early to mid-stroke. The outcomes of this study will hold significant implications for future clinical applications in rehabilitation. Trial registration Chinese Clinical Trial Registry (ChiCTR), ID: ChiCTR2100054897. Registered on 28 December 2021.

Bacterial spores are extremely resistant to various processing techniques attributable to its special structure and physiological processes, and often lead to the spoilage of thermally sterilized food. Therefore, it is of great significance to inactivate spores or control spore germination in the food industry. This review summarizes the structure and the sporulation regulation mechanism in the formation process of bacterial spores, germination process and the factors of spore germination; then reviews the effects and mechanisms of action of some physical technologies (i.e., heat treatment, ultrasonic treatment, high pressure treatment and plasma treatment), chemical technologies (i.e., surfactants and chemical preservatives) and natural bio-antibacterial agents individually or in combination with other treatments against spore. This review is expected to provide reference for the development of safer and more efficient control technology of bacterial spores.

Converting low-grade thermal energy into electrical energy is crucial for the development of modern smart wearable energy technologies. The free-standing films of PEDOT@Bi2Te3 prepared by tape-casting hold promise for flexible thermoelectric technology in self-powered sensing applications. Bi2Te3 nanosheets fabricated by the solvothermal method are tightly connected with flat-arranged PEODT molecules, forming an S-Bi bonded interface in the composite materials, and the bandgap is reduced to 1.63 eV. Compared with the PEDOT film, the mobility and carrier concentration of the composite are significantly increased at room temperature, and the conductivity reaches 684 S/cm. Meanwhile, the carrier concentration decreased sharply at 360 K indicating the creation of defect energy levels during the interfacial reaction of the composites, which increased the Seebeck coefficient. The power factor was improved by 68.9% compared to PEDOT. In addition, the introduction of Bi2Te3 nanosheets generated defects and multidimensional interfaces in the composite film, which resulted in weak phonon scattering in the conducting polymer with interfacial scattering. The thermal conductivity of the film is decreased and the ZT value reaches 0.1. The composite film undergoes 1500 bending cycles with a 14% decrease in conductivity and has good flexibility. This self-supporting flexible thermoelectric composite film has provided a research basis for low-grade thermal energy applications.

Multiple organs and tissues coordinate to respond to dietary and environmental challenges. It is interorgan crosstalk that contributes to systemic metabolic homeostasis. The liver and brain, as key metabolic organs, have their unique dialogue to transmit metabolic messages. The interconnected pathogenesis of liver and brain is implicated in numerous metabolic and neurodegenerative disorders. Recent insights have positioned the liver not only as a central metabolic hub but also as an endocrine organ, capable of secreting hepatokines that transmit metabolic signals throughout the body via the bloodstream. Metabolites from the liver or gut microbiota also facilitate a complex dialogue between liver and brain. In parallel to humoral factors, the neural pathways, particularly the hypothalamic nuclei and autonomic nervous system, are pivotal in modulating the bilateral metabolic interplay between the cerebral and hepatic compartments. The term “liver–brain axis” vividly portrays this interaction. At the end of this review, we summarize cutting-edge technical advancements that have enabled the observation and manipulation of these signals, including genetic engineering, molecular tracing, and delivery technologies. These innovations are paving the way for a deeper understanding of the liver–brain axis and its role in metabolic homeostasis.

Abstract Schizophrenia is characterized by dysconnectivity syndrome. Evidence of widespread impairment of structural and functional integration has been demonstrated in schizophrenia. Although white matter (WM) microstructural abnormalities have been commonly reported in schizophrenia, the dysfunction of WM as well as the relationship between structure and function in WM remains uncertain. In this study, we proposed a novel structure-function coupling measurement to reflect neuronal information transfer, which combined spatial-temporal correlations of functional signals with diffusion tensor orientations in the WM circuit from functional and diffusion magnetic resonance images (MRI). By analyzing MRI data from 75 individuals with schizophrenia (SZ) and 89 healthy volunteers (HV), the associations between structure and function in WM regions in schizophrenia were examined. Randomized validation of the measurement was performed in the HV group to confirm the capacity of the neural signal transferring along the WM tracts, referring to quantifying the association between structure and function. Compared to HV, SZ showed a widespread decrease in the structure-function coupling within WM regions, involving the corticospinal tract and the superior longitudinal fasciculus. Additionally, the structure-function coupling in the WM tracts was found to be significantly correlated with psychotic symptoms and illness duration in schizophrenia, suggesting that abnormal signal transfer of neuronal fiber pathways could be a potential mechanism of the neuropathology of schizophrenia. This work supports the dysconnectivity hypothesis of schizophrenia from the aspect of circuit function, and highlights the critical role of WM networks in the pathophysiology of schizophrenia.

BackgroundThe contribution of long-term ambient PM2.5 exposure to hypertension should not be ignored. However, the conclusions of whether dietary factors play a role in regulating PM2.5-related hypertension are still inconsistent. ObjectiveTo explore the correlation between long-term exposure to ambient PM2.5 and blood pressure indicators (systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure) in adults in Ningxia and a potential moderating effect of dietary factors. MethodsA set of cross-sectional survey data from March, 2013 to May, 2018 was retrieved from the China Northwest Cohort-Ningxia, and the average ambient PM2.5 concentration in the previous three years was also collected to estimate the long-term exposure of the participants. Binary logistic regression model was used to validate the correlation between long-term exposure to ambient PM2.5 and hypertension in Ningxia, and linear model was used to study the correlation between long-term exposure to ambient PM2.5 and blood pressure indicators (systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure), and to explore the influence of dietary factors on ambient PM2.5-related hypertension. ResultsA total of 11470 participants were included in the study, 42.2% male and 57.8% female. The three-year average ambient PM2.5 concentration before the baseline survey was 37.0 μg·m−3. Each 1 μg·m−3 increase in ambient PM2.5 was associated with an increased risk of hypertension (OR=1.111, 95%CI: 1.097, 1.125), and increased systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure by 0.886 (95%CI: 0.783, 0.990), 0.570 (95%CI: 0.500, 0.641), 0.676 (95%CI: 0.600, 0.751), and 0.316 (95%CI: 0.243, 0.389) mmHg, respectively. The stratified analysis showed that the OR and 95%CI of hypertension were 1.171 (1.097, 1.254), 1.117 (1.064, 1.174), and 1.160 (1.116, 1.207) respectively for each 1 μg·m−3 increased in PM2.5 with low frequency of vegetable and fruit consumption and salty taste respectively. The OR and 95%CI of hypertension were decreased when the moderate and high frequency of vegetable and fruit intake and moderate and light taste applied, the values were 1.091 (1.062, 1.121) and 1.114 (1.097, 1.131), 1.105 (1.082, 1.129) and 1.111 (1.092, 1.13), 1.115 (1.090, 1.140) and 1.102 (1.083, 1.121) respectively. Compared with low frequency of vegetable and fruit intake and salty taste, the increase degree of ambient PM2.5 related systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure also decreased in middle and high frequency of vegetable and fruit intake and moderate and light taste. ConclusionLong-term exposure to ambient PM2.5 is significantly associated with increased risks of hypertension and blood pressure in Ningxia area. Increasing the frequency of vegetable and fruit intake and decreasing salty taste may reduce the effect of ambient PM2.5 on hypertension and blood pressure.

BackgroundThe move away from investigating mental disorders as whole using sum scores to the analysis of symptom-level interactions using network analysis has provided new insights into comorbidities. The current study explored the dynamic interactions between depressive and anxiety symptoms in older Chinese adults with diabetes mellitus (DM) and identified central and bridge symptoms in the depression-anxiety network to provide potential targets for prevention and intervention for depression and anxiety.MethodsThis study used a cross-sectional design with data from the 2017–2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A regularized partial correlation network for depressive and anxiety symptoms was estimated based on self-reported scales completed by 1685 older adults with DM aged 65 years or older. Depressive and anxiety symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) and the Seven-Item Generalized Anxiety Disorder Scale (GAD-7), respectively. Expected influence (EI) and bridge expected influence (BEI) indices were calculated for each symptom.ResultsAccording to cutoff scores indicating the presence of depression and anxiety, the prevalences of depression and anxiety in our sample were 52.9% and 12.8%, respectively. The comorbidity rate of depression and anxiety was 11.5%. The six edges with the strongest regularized partial correlations were between symptoms from the same disorder. “Feeling blue/depressed”, “Nervousness or anxiety”, “Uncontrollable worry”, “Trouble relaxing”, and “Worry too much” had the highest EI values. “Nervousness or anxiety” and “Everything was an effort” exhibited the highest BEI values.ConclusionCentral and bridge symptoms were highlighted in this study. Targeting these symptoms may be effective in preventing the comorbidity of depressive and anxiety symptoms and facilitate interventions in older Chinese adults with DM who are at risk for or currently have depressive and anxiety symptoms.

Coordination is crucial for individuals to achieve common goals; however, the causal relationship between coordination behavior and neural activity has not yet been explored. Interbrain synchronization (IBS) and neural efficiency in cortical areas associated with the mirror neuron system (MNS) are considered two potential brain mechanisms. In the present study, we attempted to clarify how the two mechanisms facilitate coordination using hypertranscranial electrical stimulation (hyper-tES). A total of 124 healthy young adults were randomly divided into three groups (the hyper-tACS, hyper-tDCS and sham groups) and underwent modulation of the right inferior frontal gyrus (IFG) during functional near-infrared spectroscopy (fNIRS). Increased IBS of the PFC or neural efficiency of the right IFG (related to the MNS) was accompanied by greater coordination behavior; IBS had longer-lasting effects on behavior. Our findings highlight the importance of IBS and neural efficiency of the frontal cortex for coordination and suggest potential interventions to improve coordination in different temporal windows.

The growing number of long COVID cases has drawn clinical attention to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has been spreading worldwide since winter 2019. Its symptoms are not limited to fatigue and shortness of breath but also affect daily life. We report the use of metagenomic next-generation sequencing (mNGS) to detect coinfection with SARS-CoV-2 and influenza A virus in a patient with long COVID. The patient was admitted with fever, expectoration, fatigue, and shortness of breath. The PCR test was negative due to possible clearance of SARS-Cov-2 in the upper respiratory tract of patients with long COVID. Other routine microbiological tests were also negative, making the clinical diagnosis difficult. Bronchoalveolar lavage fluid (BALF) samples were tested using mNGS. The patient was diagnosed and treated promptly, recovered quickly, and continued taking azvudine after discharge; his condition was stable. This study illustrates that mNGS may be valuable for the timely diagnosis of patients with long COVID and their mixed infections.

Background: Immunity and ferroptosis often play a synergistic role in the progression and treatment of hepatocellular carcinoma (HCC). However, few studies have focused on identifying immune-related ferroptosis gene biomarkers.Methods: We performed weighted gene co-expression network analysis (WGCNA) and random forest to identify prognostic differentially expressed immune-related genes (PR-DE-IRGs) highly related to HCC and characteristic prognostic differentially expressed ferroptosis-related genes (PR-DE-FRGs) respectively to run co-expression analysis for prognostic differentially expressed immune-related ferroptosis characteristic genes (PR-DE-IRFeCGs). Lasso regression finally identified 3 PR-DE-IRFeCGs for us to construct a prognostic predictive model. Differential expression and prognostic analysis based on shared data from multiple sources and experimental means were performed to further verify the 3 modeled genes’ biological value in HCC. We ran various performance testing methods to test the model’s performance and compare it with other similar signatures. Finally, we integrated composite factors to construct a comprehensive quantitative nomogram for accurate prognostic prediction and evaluated its performance.Results: 17 PR-DE-IRFeCGs were identified based on co-expression analysis between the screened 17 PR-DE-FRGs and 34 PR-DE-IRGs. Multi-source sequencing data, QRT-PCR, immunohistochemical staining and testing methods fully confirmed the upregulation and significant prognostic influence of the three PR-DE-IRFeCGs in HCC. The model performed well in the performance tests of multiple methods based on the 5 cohorts. Furthermore, our model outperformed other related models in various performance tests. The immunotherapy and chemotherapy guiding value of our signature and the comprehensive nomogram’s excellent performance have also stood the test.Conclusion: We identified a novel PR-DE-IRFeCGs signature with excellent prognostic prediction and clinical guidance value in HCC.

BackgroundAcute stress reaction (ASR) following a stressful event is associated with stress-related mental disorders. However, no studies have investigated the relationships between ASR symptom clusters. The present study aimed to provide a fine-grained understanding of the complex relationships among symptom clusters and identify the central symptom clusters of ASR using network analysis.MethodsThe Acute Stress Reaction Scale (ASRS) was used to investigate the network structure of ASR in 1792 Chinese male military college students who were about to participate in an important physical fitness test. We calculated the weights of the edges connecting different symptom clusters and the central indices of 25 symptom clusters in the final network.ResultsThere were five strongest edges with significantly higher weights than most other edge weights, including the edges between “Less communication” and “Isolated from others.” The symptom clusters of “Somatic symptoms,” “Hypoprosexia,” and “Anxiety” were found to be the central nodes with the highest expected influences (primary centrality index).ConclusionThe present study explored the network structure of ASR, revealed complex connections between symptom clusters, and identified central clusters. These findings have important clinical implications, and it is suggested that the three central symptom clusters may be potential targets for effective interventions for ASR.

Based on deep neural network, elliptic partial differential equations in complex regions are solved. Accurate and effective strategies and numerical methods for elliptic partial differential equations are proposed by implementing deep feedforward artificial neural network, appropriate loss function solving strategy are constructed. The solution of an elliptic partial differential equation is obtained by iteratively learning the parameters of a neural network. Constructing a composite multi-layer radial basis function neural network can improve the real function approximation performance and operational accuracy of the constructed multi-layer radial basis function neural network. Use this high-precision composite multi-layer radial basis function neural network to solve partial differential equations. By providing specific examples of solving partial differential equations, the effectiveness of this method is tested. An improved partial differential equation solving method based on deep neural networks (Taylor PINN) has been proposed. This method utilizes the universal approximation theorem of deep neural networks and the function fitting ability of Taylor’s formula to achieve a meshless numerical solution process. The numerical experimental results on Helmholtz, Klein Gordon, and Navier Stokes equations show that Taylor PINN can well fit the mapping relationship between the coordinates of spatiotemporal points in the computational domain and the value of the desired function, which can provide accurate numerical prediction results. Compared with commonly used physical information based neural network methods, Taylor PINN improves prediction accuracy by 3–20 times for different numerical problems.

Changes in land surface properties during urbanization have a significant impact on variations in precipitation. Little research has been carried out on spatial heterogeneity and influence strength of the driving factors of precipitation changes at different urbanization scales. Using a trend analysis and multi-scale geographically weighted regression, this study analysed the spatial heterogeneity and impact scale of driving factors of precipitation changes in 156 urban units in the Beijing-Tianjin-Hebei urban agglomeration region (Jing-Jin-Ji). In summer, RAD (radiation), RHU (relative humidity), WIN (wind speed), and POP (urban population density) were found to act on a small regional scale, AOD (aerosol optical depth) on a medium regional scale, and NDVI (normalized difference vegetation index), NLI (night time light intensity), UHI (urban heat island intensity), and AREA (urban area size) on a global scale. In winter, AREA and WIN acted on a medium regional scale, UHI on a large regional scale, and AOD, NDVI and NLI on a global scale. Across the whole year, NDVI and AREA had a medium regional impact and NLI a large regional one. Variations in natural factors, such as RAD and RHU, had a great influence on the spatial heterogeneity of precipitation changes, whereas human factors, such as NLI and UHI, had a small influence. In summer, AOD mainly affected Tangshan and Qinhuangdao in the northeast and Cangzhou in the southeast of the Jing-Jin-Ji. RHU and AREA primarily affected the cities of Handan and Xingtai. In winter, NLI, AREA, WIN, and UHI had significant effects in the cities of Handan and Xingtai, with AREA being the most important factor. In the Shijiazhuang-Hengshui area, RAD and NLI played a significant role; in the Beijing-Zhangjiakou-Chengde area, the most important factor affecting precipitation changes was the variation in POP. These results provide a scientific basis for flood disaster risk management in the Jing-Jin-Ji and the establishment of differentiated climate policies in different cities.

Background Checkpoint inhibitor pneumonitis (CIP) that does not respond to corticosteroids is termed steroid-refractory CIP. We aimed to find risk factors of steroid-refractory CIP and evaluate the management strategies of immunomodulators (IMs).Methods Patients with CIP were identified between August 2019 and August 2022 retrospectively. Clinical characteristics, peripheral blood biomarkers, and radiologic images were collected.Results Among 1209 patients with solid tumor receiving programmed death (ligand)-1 antibody, 28 patients developed steroid-refractory CIP and 38 patients developed steroid-response CIP. Patients with steroid-refractory CIP had a higher proportion of previous interstitial lung disease (p=0.015) and grade 3–4 (p

Chemical preservatives are used to control spoilage microorganisms in food. Preservative residues have certain potential hazards to the human body. In this paper, lactic acid bacteria resistant to food spoilage fungi were screened and compounded and mixed fermentation were carried out to improve the antifungal activity of the fermentation broth. The 24-well double-layer agar method and the graded inhibitory concentration method were used to screen the more antifungal strains from multiple strains of lactic acid bacteria and Propionibacterium and determine the optimal combination of mixed bacteria. Through the Plackett-Burman test and the steepest climbing test, the fermentation process was optimized, and the antifungal activity of the fermentation supernatant was measured with a 96-well plate microplate reader method. The results showed that the optimal combination of mixed bacteria was Lactobacillus plantarum L9 and Propionibacterium frederi D5. The optimized formula of fermentation medium: Glucose 55.0 g/L, calcium carbonate 6.7 g/L, yeast extract 14.8 g/L, hydrogen phosphate dipotassium 0.25 g/L, manganese sulfate 0.1 g/L, sodium acetate 5.0 g/L, ammonium citrate 2.0 g/L, the inoculation ratio was 5:1 (D5:L9), and the fermentation temperature was 37 °C. The optimized fermentation medium of the selected L9 and D5 was verified by mixed fermentation, and the antifungal activity of the fermentation broth could be as high as 47.07AU.

Abstract Background Endophytic bacteria have been demonstrated to be one of the most potentially important biocontrol agents for their efficiently improved plant growth and protection of host plants from infection by phytopathogens. Results Nine strains of endophytic bacteria isolated from Glycyrrhiza uralensis Fisch. (G. uralensis) seeds were screened for the inhibitory effect against 5 fungal phytopathogens by using dual culture method. Among which, the isolate FT2 showed the highest percentage of inhibition to all the test fungal phytopathogens. Detached root assay showed that FT2 significantly reduced disease index and rotted area on Angelica sinensis root slices caused by Fusarium acuminatum. FT2 also exhibited multiple plant growth promotion traits by qualitative analytical method. Based on phenotypic, physiological and biochemical characterization and genotypic characterization, the FT2 strain was identified as Stenotrophomonas rhizophila. Application of strain FT2 reduced the disease index of Cucumber Fusarium Wilt, and the biocontrol effect was equal to chemical fungicide, carbendazim. Moreover, strain FT2 increased the plant height, stem diameter, leaf number and fresh weight of cucumber seedlings and the activities of the defense-related enzymes including phenylalanine ammonia-lyase, polyphenol oxidase and peroxidase. In addition, strain FT2 could promote seed germination and seedling growth of G. uralensis and increase enzyme activities, available nutrient contents and bacterial count in G. uralensis rhizosphere soil. Conclusions The results demonstrated that the strain FT2 could be used to develop environmentally friendly microbial products to improve the activity against pathogenic and promote plant growth.

Summary: Hepatic metastasis is the leading cause of colorectal-cancer (CRC)-associated death. Here we describe an optimized protocol to establish a more clinically relevant mouse model of CRC metastasis. We detail steps for subcutaneous transplantation of luciferase-expressing CRC cells and subsequent orthotopic transplantation of subcutaneous tumor tissues. This mouse model allows CRC cells to form tumors within the intestinal tract and metastasize to the liver, thereby providing the approach to assess hepatic metastasis of CRC in vivo.For complete details on the use and execution of this protocol, please refer to Zhang et al. (2021).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Air pollution has become one of the most important public health problems worldwide. Exposure to air pollution during pregnancy is one of the important risk factors for adverse birth outcomes such as preterm birth, low birth weight, and birth defects. Air pollution control has a long way to go. Therefore, it is extremely urgent to analyze and identify relevant protective factors. Some studies have shown that green space may be a protective factor for the adverse birth outcomes related to air pollution. This kind of research mainly utilizes satellite monitoring data, quantifies the green space coverage level in a certain range of buffer zone centered on the pregnant women's home addresses, and analyzes its mediation effect on the adverse pregnancy outcomes related to air pollution. In this paper we reviewed the use of green space data, the estimated effect of green space mediating the relationship between air pollution and adverse birth outcomes, and its possible mechanisms, aiming to clarify the impact of green space on adverse birth outcomes related to air pollution and provide a scientific basis for public health intervention strategies.

Measurement(s) road density • PM2.5 • NDVI Technology Type(s) open street map, google map • satellite-, simulation- and monitor-based PM2.5 sources • Moderate resolution Imaging Spectroradiometer Factor Type(s) ServiceNam • ServiceTyp • ServiceAdd • Suburb • State • Postcode • NumberOfAp • QualityAre • OverallRat • Long_Day_C • Preschool_ • Outside_sc • type • lon_final.x • lat_final.x • PM2.5_2013 • PM2.5_2014 • PM2.5_2015 • PM2.5_2016 • PM2.5_2017 • PM2.5_2018 • NDVIMax_2013 • NDVIMax_2014 • NDVIMax_2015 • NDVIMax_2016 • NDVIMax_2017 • NDVIMax_2018 • NDVIMax_2019 • dismain • dismotorway • main_50 • main_100 • main_300 • main_500 • main_1000 • moto_50 • moto_100 • moto_300 • moto_500 • moto_1000 Sample Characteristic - Organism child care center Sample Characteristic - Environment road density • PM2.5 • NDVI Sample Characteristic - Location Australia

Forests not only are an essential resource for human society but also have a significant impact on the climate. With the development of remote sensing technology, some progress has been made in forest change monitoring. However, relatively little research has been conducted on historical forest dynamics. Estimating forest loss and its drivers during historical time periods remains a scientific pursuit. In this study, we reconstructed forest loss and its dominant drivers across China based on long time-series socioeconomic and environmental data using LightGBM classification and regression models. The models showed good performance in both 10-fold cross-validation and comparison with other datasets. The results indicate that from 1900 to 2000, forest loss mainly occurred in southern China, with a total loss area of 34.4 × 104 km2. Additionally, there was significant spatial heterogeneity, showing a decreasing trend from east to west and from south to north. The forest loss in China can be divided into two stages: (1) the stable stage from 1900 to 1949; and (2) the fluctuating stage from 1950 to 1999. In the first stage, most of the forest loss was attributed to forestry (>80%), followed by commodity-driven deforestation. In the early stage of the development of the People’s Republic of China, forest loss showed an increasing trend. In the 1960s, the forest loss area decreased by 12.9% due to the stagnation of the economy. With the adoption of the reform and opening-up policy, the total forest loss area in China reached its peak value (6.4 × 104 km2) during 1980–1989. The models also accurately captured the impact of urbanization and government policy in this period. This study not only provides an in-depth understanding of historical forest change in China, but also offers data and methodological references for the further study of human–nature interactions over the long term.

Accumulating evidence showed that major depressive disorder (MDD) is characterized by a dysfunction of serotonin neurotransmission. Raphe nuclei are the sources of most serotonergic neurons that project throughout the brain. Incorporating measurements of activity within the raphe nuclei into the analysis of connectivity characteristics may contribute to understanding how neurotransmitter synthesized centers are involved in the pathogenesis of MDD. Here, we analyzed the resting-state functional magnetic resonance imaging (RS-fMRI) dataset from 1,148 MDD patients and 1,079 healthy individuals recruited across nine centers. A seed-based analysis with the dorsal raphe and median raphe nuclei was performed to explore the functional connectivity (FC) alterations. Compared to controls, for dorsal raphe, the significantly decreased FC linking with the right precuneus and median cingulate cortex were found; for median raphe, the increased FC linking with right superior cerebellum (lobules V/VI) was found in MDD patients. In further exploratory analyzes, MDD-related connectivity alterations in dorsal and median raphe nuclei in different clinical factors remained highly similar to the main findings, indicating these abnormal connectivities are a disease-related alteration. Our study highlights a functional dysconnection pattern of raphe nuclei in MDD with multi-site big data. These findings help improve our understanding of the pathophysiology of depression and provide evidence of the theoretical foundation for the development of novel pharmacotherapies.

IntroductionBased on the compensatory Internet use theory and diathesis-stress model, the present study explores the effects of chronic stress on smartphone addiction (SPA). As intolerance of uncertainty and emotion-related variables are important factors that affect addictive behavior, we explore the mediating role of intolerance of uncertainty and the moderating role of emotion differentiation.MethodsWe conducted a questionnaire survey of 286 participants (13.64% female; Mage = 22.88; SD = 3.77; range = 17–39) on chronic stress, SPA, intolerance of uncertainty, and emotion differentiation. SPSS 28.0 was used to analyze the descriptive statistics and correlations and test the moderated mediation model.ResultsWe find that (1) intolerance of uncertainty, SPA, and chronic stress are positively correlated with each other. Positive emotion differentiation is positively correlated with intolerance of uncertainty and negative emotion differentiation. (2) Intolerance of uncertainty plays a mediating role in chronic stress and SPA. (3) Positive emotion differentiation significantly moderates the relationship between chronic stress and SPA. Under the condition of low positive emotion differentiation, chronic stress is more effective in predicting SPA.DiscussionThese findings may contribute to intervention and prevention programs for SPA. Thus, the intervention and prevention of SPA can start from two directions-reduce the intolerance of uncertainty and enhance the ability to experience positive emotion differentiation.

Abstract Background Immune‐based combination therapies have revolutionized the first‐line treatment for advanced non‐small cell lung cancer (NSCLC). However, for the efficacy and safety, the best treatment option is still uncertain. Methods We conducted a Bayesian network meta‐analysis of randomized controlled trials (RCTs) to evaluate first‐line immune‐based combination therapies for advanced NSCLC. Results Fourteen trials involving 8467 patients were included. For the programmed cell death‐ligand 1 (PD‐L1) expression non‐selective patients, there were no significant differences among all the treatment modes for overall survival (OS), but the ranking profiles indicated that Immunotherapy + Immunotherapy + Chemotherapy (IO + IO + Chemo) was most likely to be the best mode (probability = 68%). Immunotherapy + Immunotherapy + Anti‐angiogenic therapy + Chemotherapy (IO + Anti‐angio + Chemo) was significantly better than most other treatment modes for progression‐free survival (PFS) with better objective response rate (ORR) and more obvious grade ≥3 treatment‐related adverse events (TRAEs). In PD‐L1‐high cohort, IO + Anti‐angio + Chemo seemed to be the best mode for OS, PFS, and ORR according to the ranking profiles. In PD‐L1‐intermediate and PD‐L1‐negative cohort, IO + IO + Chemo was inclined to be ranked first for prolonging OS (probability = 78%; 37%) and IO + Anti‐angio + Chemo was most likely to provide best PFS (probability = 96%; 100%). Conclusion IO + IO + Chemo has great potential to improve the OS regardless of histology type, especially in PD‐L1‐intermediate and PD‐L1‐negative cohort. IO + Anti‐angio + Chemo shows great superiority in improving the short‐term survival accompanied by increasing grade ≥3 TRAEs.

Vascular smooth muscle cell (VSMC) migration plays a critical role in the pathogenesis of many cardiovascular diseases. We recently showed that TMEM16A is involved in hypertension-induced cerebrovascular remodeling. However, it is unclear whether this effect is related to the regulation of VSMC migration. Here, we investigated whether and how TMEM16A contributes to migration in basilar artery smooth muscle cells (BASMCs). We observed that AngII increased the migration of cultured BASMCs, which was markedly inhibited by overexpression of TMEM16A. TMEM16A overexpression inhibited AngII-induced RhoA/ROCK2 activation, and myosin light chain phosphatase (MLCP) and myosin light chain (MLC20) phosphorylation. But AngII-induced myosin light chain kinase (MLCK) activation was not affected by TMEM16A. Furthermore, a suppressed activation of integrinβ3/FAK pathway, determined by reduced integrinβ3 expression, FAK phosphorylation and F-actin rearrangement, was observed in TMEM16A-overexpressing BASMCs upon AngII stimulation. Contrary to the results of TMEM16A overexpression, silencing of TMEM16A showed the opposite effects. These in vitro results were further demonstrated in vivo in basilar arteries from VSMC-specific TMEM16A transgenic mice during AngII-induced hypertension. Moreover, we observed that the inhibitory effect of TMEM16A on BASMC migration was mediated by decreasing the activation of WNK1, a Cl−-sensitive serine/threonine kinase. In conclusion, this study demonstrated that TMEM16A suppressed AngII-induced BASMC migration, thus contributing to the protection against cerebrovascular remodeling during AngII-infused hypertension. TMEM16A may exert this effect by suppressing the RhoA/ROCK2/MLCP/MLC20 and integrinβ3/FAK signaling pathways via inhibiting WNK1. Our results suggest that TMEM16A may serve as a novel therapeutic target for VSMC migration-related diseases, such as vascular remodeling.

Background Cardiac magnetic resonance image (MRI) has been widely used in diagnosis of cardiovascular diseases because of its noninvasive nature and high image quality. The evaluation standard of physiological indexes in cardiac diagnosis is essentially the accuracy of segmentation of left ventricle (LV) and right ventricle (RV) in cardiac MRI. The traditional symmetric single codec network structure such as U-Net tends to expand the number of channels to make up for lost information that results in the network looking cumbersome. Methods Instead of a single codec, we propose a multiple codecs structure based on the FC-DenseNet (FCD) model and capsule convolution-capsule deconvolution, named Nested Capsule Dense Network (NCDN). NCDN uses multiple codecs to achieve multi-resolution, which makes it possible to save more spatial information and improve the robustness of the model. Results The proposed model is tested on three datasets that include the York University Cardiac MRI dataset, Automated Cardiac Diagnosis Challenge (ACDC-2017), and the local dataset. The results show that the proposed NCDN outperforms most methods. In particular, we achieved nearly the most advanced accuracy performance in the ACDC-2017 segmentation challenge. This means that our method is a reliable segmentation method, which is conducive to the application of deep learning-based segmentation methods in the field of medical image segmentation.

Background: Evidence regarding the association between particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5) and blood lipid levels is insufficient in the rural areas of developing countries. Few studies have estimated the role of PM2.5 in blood lipid levels. We investigated the relationship between long-term exposure to PM2.5, blood lipids, and dyslipidaemia in rural Chinese adults.Methods: Baseline data of 15,802 participants (aged 35–74 years) in the China Northwest Cohort-Ningxia Project were used in this study. PM2.5 levels were assessed using satellite remote sensing data in accordance with each participant’s home address. Personally exposed PM2.5 was defined as the 3-year mean concentration prior to the baseline survey. Logistic and linear models were utilised to quantify the associations of PM2.5 with the prevalence of dyslipidaemia and with blood lipids, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C).Results: The 3-year mean level of PM2.5 was 35.36 ± 4.21 μg/m3. Every 1-μg/m3 increase in PM2.5 was related to an increase of 0.04% (95% CI: −0.44–0.53%) in TG and decreases of 0.37% (95% CI: 0.16–0.90%) in TC, 5.76% (95% CI: 5.32–6.21%) in LDL-C, and 0.89% (95% CI: 0.72–1.05%) in HDL-C. Every 1-μg/m3 increment in PM2.5 was related with a 4% (95% CI:3–5%) and 18% (95% CI:16–20%) higher risk of dyslipidaemia and hypoalphalipoproteinemia, respectively, and a decrease of 11% (95% CI:10–13%) in hyperbetalipoproteinemia. Sex, age, and BMI were adjusted for the relationships between PM2.5, blood lipids, and dyslipidaemia.Conclusion: Greater PM2.5 exposure was related to harmful changes in blood lipids and dyslipidaemia. Male, elderly, and overweight individuals may be more vulnerable to the negative effects of PM2.5.

Many studies have illustrated the close relationship between anxiety disorders and attentional functioning, but the relationship between trait anxiety and attentional bias remains controversial. This study examines the effect of trait anxiety on the time course of attention to emotional stimuli using materials from the International Affective Picture System. Participants with high vs. low trait anxiety (HTA vs. LTA) viewed four categories of pictures simultaneously: dysphoric, threatening, positive, and neutral. Their eye-movements for each emotional stimulus were recorded for static and dynamic analysis. Data were analyzed using a mixed linear model and growth curve analysis. Specifically, the HTA group showed a greater tendency to avoid threatening stimuli and more pupil diameter variation in the early period of stimulus presentation (0–7.9 s). The HTA group also showed a stronger attentional bias toward positive and dysphoric stimuli in the middle and late period of stimulus presentation (7.9–30 s). These results suggest that trait anxiety has a significant temporal effect on attention to emotional stimuli, and that this effect mainly manifests after 7 s. In finding stronger attentional avoidance of threatening stimuli and more changes in neural activity, as well as a stronger attentional bias toward positive stimuli, this study provides novel insights on the relationship between trait anxiety and selective attention.

IntroductionCheckpoint inhibitor pneumonitis (CIP) is a common serious adverse event caused by immune checkpoint inhibitors (ICIs), and severe CIP can be life-threatening. We aimed to investigate the role of peripheral blood cells in diagnosis, prediction, and prognosis evaluation for all and severe CIP.Materials and methodsPatients with lung cancer receiving ICIs were enrolled in this retrospective study. Baseline was defined as the time of ICI initiation, endpoint was defined as the time of clinical diagnosis of CIP or the last ICI treatment, and follow-up point was defined as 1 week after CIP. Eosinophil percentages at baseline, endpoint, and follow-up point were shortened to “Ebas”, “Eend and “Efol”, respectively.ResultsAmong 430 patients included, the incidence of CIP was 15.6%, and severe CIP was 3.7%. The Eend/Ebas value was lower in patients with CIP (p = 0.001), especially severe CIP (p = 0.036). Receiver operating characteristic curves revealed that Eend/Ebas could serve as a biomarker to diagnose CIP (p = 0.004) and severe CIP (p < 0.001). For severe CIP, the eosinophil percentage declined before the symptoms appeared and CT diagnosis. The eosinophil percentage significantly elevated at the follow-up point in the recovery group but not in the non-recovery group. The CIP patients with Efol/Ebas ≥1.0 had significantly prolonged overall survival (p = 0.024) and after-CIP survival (AS) (p = 0.043). The same results were found in severe CIP but without a statistical difference.ConclusionsEosinophil percentage was associated with the diagnosis, prediction, and prognosis of CIP and severe CIP.

Objective: Quantifying the spatial and socioeconomic variation of mortality burden attributable to particulate matters with aerodynamic diameter ≤ 2.5 µm (PM2.5) has important implications for pollution control policy. This study aims to examine the regional and socioeconomic disparities in the mortality burden attributable to long-term exposure to ambient PM2.5 in China. Methods: Using data of 296 cities across China from 2015 to 2019, we estimated all-cause mortality (people aged ≥ 16 years) attributable to the long-term exposure to ambient PM2.5 above the new WHO air quality guideline (5 µg/m3). Attributed fraction (AF), attributed deaths (AD), attributed mortality rate (AMR) and total value of statistical life lost (VSL) by regional and socioeconomic levels were reported. Results: Over the period of 2015–2019, 17.0% [95% confidence interval (CI): 7.4–25.2] of all-cause mortality were attributable to long-term exposure to ambient PM2.5, corresponding to 1,425.2 thousand deaths (95% CI: 622.4–2,099.6), 103.5/105 (95% CI: 44.9–153.3) AMR, and 1006.9 billion USD (95% CI: 439.8–1483.4) total VSL per year. The AMR decreased from 120.5/105 (95% CI: 52.9–176.6) to 92.7/105 (95% CI:39.9–138.5) from 2015 to 2019. The highest mortality burden was observed in the north region (annual average AF = 24.2%, 95% CI: 10.8–35.1; annual average AMR = 137.0/105, 95% CI: 60.9–198.5). The highest AD and economic loss were observed in the east region (annual average AD = 390.0 thousand persons, 95% CI: 170.3–574.6; annual total VSL = 275.6 billion USD, 95% CI: 120.3–406.0). Highest AMR was in the cities with middle level of GDP per capita (PGDP)/urbanization. The majority of the top ten cities of AF, AMR and VSL were in high and middle PGDP/urbanization regions. Conclusion: There were significant regional and socioeconomic disparities in PM2.5 attributed mortality burden among Chinese cities, suggesting differential mitigation policies are required for different regions in China.

Background: Existing evidence suggests that mumps epidemics, a global public health issue, are associated with meteorological factors and air pollutants at the population scale. However, the interaction effect of meteorological factors and air pollutants on mumps remains underexplored.Methods: Daily cases of mumps, meteorological factors, and air pollutants were collected in Ningxia, China, from 2015 to 2019. First, a distributed lag nonlinear model (DLNM) was employed to assess the confounding-adjusted relationship between meteorological factors, ambient air pollutants, and mumps incidences. According to the results of DLNM, stratification in both air pollutants and meteorological factors was adopted to further explore the interaction effect of particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM2.5) and ground-level ozone (O3) with temperature and relative humidity (RH).Results: We reported significant individual associations between mumps incidences and environmental factors, including temperature, relative humidity, PM2.5, and O3. Evident multiplicate and additive interactions between meteorological factors and PM2.5 were found with interaction relative risk (IRR) of 1.14 (95%CI: 1.01, 1.29) and relative excess risk due to interaction (RERI) of 0.17 (95%CI: 0.02, 0.32) for a moderate level of temperature at 12°C, and IRR of 1.37 (95%CI: 1.14, 1.66), RERI of 0.36 (95%CI: 0.11, 0.60) for a high level of temperature at 20°C, respectively. These results indicated that PM2.5 and temperature have a significant synergistic effect on the cases of mumps, while no interaction between relative humidity and PM2.5 is observed. Regarding O3 and meteorological factors (temperature = 12°C, 20°C), IRR and RERI were 1.33 (95%CI: 1.17, 1.52) and 0.30 (95%CI: 0.16, 0.45), 1.91 (95%CI: 1.46, 2.49) and 0.69 (95%CI: 0.32, 1.07), respectively. And IRR of 1.17 (95%CI: 1.06, 1.29), RERI of 0.13 (95%CI: 0.04, 0.21) for a middle level of relative humidity at 48%.Conclusion: Our findings indicated that meteorological factors and air pollutants imposed a significantly lagged and nonlinear effect on the incidence of mumps. The interaction between low temperature and O3 showed antagonistic effects, while temperature (medium and high) with PM2.5 and O3 presented synergistic effects. For relative humidity, the interaction with O3 is synergistic. These results provide scientific evidence to relevant health authorities for the precise disease control and prevention of mumps in arid and semi-arid areas.

ObjectiveThis study shares our experience in managing adrenal schwannoma (AS).MethodsThe clinical data of eight patients with AS in our hospital from April 2007 to April 2022 were analyzed retrospectively.ResultsA total of 1309 patients with adrenal lesions were treated in the affiliated hospital of Guizhou Medical University for 15 years, of which only 8 cases were diagnosed as AS, accounting for 0.61%. Among the eight patients with AS, there were five females and three males, with an average age of 48.63 ± 12.05 years, and the average maximum diameter of the tumor was 6.96 ± 1.83 cm. All patients underwent adrenalectomy and were pathologically diagnosed as AS after the operation. The average follow-up time of eight patients with AS was 60.13 ± 22.33 months, and there was no recurrence or metastasis.ConclusionThe retroperitoneum is an uncommon site for schwannoma tumors, and among adrenal incidentalomas, the schwannoma is rare. The disease lacks specific clinical and imaging features, but correct diagnosis before the pathological examination is very important for clinical management and surgical decision. When imaging examination indicates a slow-growing retroperitoneal mass, schwannoma should be considered. Surgical resection is the main treatment. Pathology is the gold standard for diagnosis. Most of the tumors are benign and have a good prognosis. There is a risk of recurrence after the operation, and it should be monitored actively.

Effective teamwork among military pilots is key to successful mission completion. The underlying neural mechanism of teamwork is thought to be inter-brain synchronization (IBS). IBS could also be explained as an incidental phenomenon of cooperative behavior, but the causality between IBS and cooperative behavior could be clarified by directly producing IBS through extra external stimuli applied to functional brain regions. As a non-invasive technology for altering brain function, transcranial electrical stimulation might have the potential to explore whether top-down enhancement of the synchronization of multiple brains can change cooperative behavioral performance among members of a team. This review focuses on the characteristic features of teamwork among military pilots and variations in neuroimaging obtained by hyper-scanning. Furthermore, we discuss the possibility that transcranial electrical stimulation could be used to improve teamwork among military pilots, try to provide a feasible design for doing so, and emphasize crucial aspects to be addressed by future research.

ObjectiveTo make a bibliometric analysis of global trends in research into exercise interventions for stroke between 2001 and 2021.MethodThis study did the systematic literature from 2001 to 2021 in Web of Science Core Collection. CiteSpace software was used to analyze the relationship of publications with countries, journals, authors, references, and keywords.ResultsA total of 3,484 publications were obtained in the bibliometric analysis. The number of publications increased gradually over the period. The United States have the most number of publications. The journal stroke had the most citations per paper (106.95) and the highest impact factor (IF 2020, 7.194). The most high frequency keywords are “stroke,” “rehabilitation,” and “recovery,” the top of burst key words are “health,” “speed,” and “aerobic exercise”.ConclusionThese findings provide the trends of exercise for stroke s and provided the potential research frontiers in the past 20 years. It will be a useful basis for further research into focus issues, cooperators, development trends.

BackgroundDrug–drug interactions (DDIs) pose new challenges beyond traditional pharmacodynamics in the context of optimizing the treatment options with immune checkpoint inhibitors (ICIs). To alleviate cancer-related pain, analgesics are of absolute vital importance as chronic medications used by cancer patients. However, the possible outcome of ICI treatment concomitant with analgesics remains unclear.MethodsOriginal articles describing the possible influence of analgesics use on ICI treatment published before December 1, 2021 were retrieved from PubMed, Embase, and the Cochrane Library. Odds ratio (OR) with 95% confidence interval (CI) for objective response rate (ORR), hazard ratio (HR) with 95% CI for progression-free survival (PFS), and overall survival (OS) were calculated using the random-effects or fixed-effects model, and heterogeneity was assessed using the χ2-based Q-test. Publication bias was examined by funnel plot analysis.ResultsA total of 11 studies involving 4,404 patients were included. The pooled OR showed that opioid use decreased the response of opioid users to ICIs compared to non-opioid users (OR = 0.49, 95% CI = 0.37–0.65, p < 0.001). Compared to patients who did not receive opioids, opioid users had an increased risk of progression and mortality (HR = 1.61, 95% CI = 1.37–1.89, p < 0.001; HR = 1.67, 95% CI =1.30–2.14, p < 0.001, respectively). Furthermore, the concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) was not significantly associated with differences in ORR, PFS, and OS in patients treated with ICIs (OR = 1.40, 95% CI = 0.84–2.32, p = 0.190; HR = 0.90, 95% CI = 0.77–1.06, p = 0.186; HR = 0.90, 95% CI = 0.71–1.14, p = 0.384, respectively).ConclusionThe concomitant use of opioids during ICI treatment has an adverse effect on patient prognosis, while the use of NSAIDs is not significantly associated with the prognosis in patients treated with ICIs.

Burn injury is a common form of traumatic injury that leads to high mortality worldwide. A severe burn injury usually induces gut barrier dysfunction, partially resulting from the impairment in the proliferation and self-renewal of intestinal stem cells (ISCs) post burns. As a main energy substance of small intestinal enterocytes, glutamine (Gln) is important for intestinal cell viability and growth, while its roles in ISCs-induced regeneration after burns are still unclear. To demonstrate the potential effects of Gln in improving ISCs proliferation and alleviating burn-induced intestinal injury, in this study, we verified that Gln significantly alleviated small intestine injury in burned mice model. It showed that Gln could significantly decrease the ferroptosis of crypt cells in the ileum, promote the proliferation of ISCs, and repair the crypt. These effects of Gln were also confirmed in the mouse small intestine organoids model. Further research found that Yes-associated protein (YAP) is suppressed after burn injury, and Gln could improve cell proliferation and accelerate the renewal of the damaged intestinal mucosal barrier after burns by activating YAP. YAP is closely associated with the changes in intestinal stem cell proliferation after burn injury and could be served as a potential target for severe burns.

The tripartite entanglement generated from a cascaded parametric amplifier is always present in the whole gain region in the ideal condition. However, in practical applications, the quantum entanglement is very fragile and easily deteriorated by quantum noise from interactions with external environments, e.g., the avoidable attenuation and amplification operations may lead to some degradation effects on the quantum entanglement. Therefore, in this work, bipartite entanglement for the three pairs and tripartite entanglement in this cascaded parametric amplifier under the circumstances of attenuation and amplification operations are analyzed by using positivity under partial transposition criterion. The results show that tripartite entanglement is robust to the deterioration effects from the attenuation and amplification operations rather than bipartite entanglement. Our results may find some practical applications of multipartite quantum entanglement in quantum secure communications.

Abstract Background Non-small cell lung cancer (NSCLC) cells derived intracellular and extracellular programmed cell death ligand 1 (PD-L1) promoted cancer progression and drug resistance, and facilitated tumor immune evasion. However, the detailed molecular mechanisms are still largely unknown. In the present study, we aimed to explore the role of circular RNA circ-CPA4/let-7 miRNA/PD-L1 axis in the regulation of NSCLC progression, drug resistance and tumor immune microenvironment. Methods Real-Time qPCR and Western Blot analysis were conducted to examine gene expressions at transcriptional and translated levels, respectively. The regulatory mechanisms of circ-CPA4, let-7 miRNA and PD-L1 were validated by dual-luciferase reporter gene system and RNA pull-down assay. Cell growth and apoptosis were determined by CCK-8 assay, colony formation assay and Annexin V-FITC/PI double staining assay. Cell mobility was evaluated by transwell assay. Results Circ-CPA4 and PD-L1 were high-expressed, while let-7 miRNA was low-expressed in NSCLC cells and cancer tissues compared to the human bronchial epithelial (HBE) cells and their paired clinical normal adjacent tissues, respectively. Besides, knock-down of circ-CPA4 inhibited cell growth, mobility and epithelial-mesenchymal transition (EMT), and promoted cell death in NSCLC cells by downregulating PD-L1 through serving as a RNA sponge for let-7 miRNA. In addition, the NSCLC cells derived PD-L1-containing exosomes promoted cell stemness and increased resistance of NSCLC cells to cisplatin. Notably, by co-culturing the NSCLC cells with CD8+ T cells isolated from human peripheral blood mononuclear cells (hPBMCs) in a transwell co-culturing system, we found that NSCLC cells inactivated CD8+ T cells in a secreted PD-L1-dependent manner. Further results suggested that circ-CPA4 also positively regulated exosomal PD-L1, and the NSCLC cells with circ-CPA4 ablation re-activated CD8+ T cells in the co-culturing system. Conclusion Taken together, circ-CPA4 regulated cell growth, mobility, stemness and drug resistance in NSCLC cells and inactivated CD8+ T cells in the tumor immune microenvironment through let-7 miRNA/PD-L1 axis.

The cold chain logistics is a special distribution process with respect to agricultural products that are sensitive to temperature. In this approach, remote sensing data and spatial analysis are the main components of china’s cold chain logistics capabilities, particularly on agricultural products. Therefore, The Cold Chain Logistics analysis on agricultural products in various provinces is evaluated using a Spatial Exploratory Data Analysis and Geo-detector approach. Hence, The characteristically Remote Sensing Spatio-Temporal Logistical Regression (RS-STLR) model has been developed to characterize both the cold chain's logistic resource and provincial differences. This paper provides a perspective on the growth and variations in Chinese logistics services for cold chain logistics. The research has been conducted at a lab-scale which established an alternate interpretation between different regional variations in logistic capital of the ecological features of the cold chain logistics. The aim of this analysis is to validate the condition of the cold chain market based on the quantitative system of risk assessment on agricultural produces.