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Abstract Background Mixed exhaled air has been widely used to determine exhaled propofol concentrations with online analyzers, but changes in dead space proportions may lead to inaccurate assessments of critical drug concentration data. This study proposes a method to correct propofol concentration in mixed air by estimating pulmonary dead space through reconstructing volumetric capnography (Vcap) from time-CO2 and time-volume curves, validated with vacuum ultraviolet time-of-flight mass spectrometry (VUV-TOF MS). Methods Existing monitoring parameters, including time-volume and time-CO2 curves, were used to determine Vcap. The ratio of physiological dead space to tidal volume (VD/VT) was calculated using Bohr’s formula. Additionally, an animal experiment on beagles was conducted with continuous propofol administration until a pseudo-steady state in exhaled propofol concentration was achieved. The propofol concentration in mixed air (CONCmix), and in alveolar air combined with N2 (CONCAN) were measured using VUV-TOF MS to calculate VD/VT. The agreements between VD/VT values from the two methods, along with the predicted CONCAN values based on Vcap and the actual measured CONCAN values were evaluated using the intraclass correlation coefficient (ICC) and Pearson correlation analysis. Results After 30 min of continuous propofol administration, a stable respiratory cycle was selected for analysis in each beagle. The calculated VD/VT-Bohr values were 0.535 for beagle A, 0.544 for beagle B, and 0.552 for beagle C. Additionally, based on CONCmix and CONCAN, the calculated VD/VT-VUV-TOF MS values were 0.494, 0.504, and 0.513, respectively. Strong agreement between the two methods was demonstrated by an ICC of 0.994 (P = 0.003) and Pearson’s r of 0.995 (P = 0.045). Additionally, the predicted CONCAN values from mixed exhaled air (5.11 parts per billion by volume (ppbv) for beagle A, 5.93 ppbv for beagle B, and 2.56 ppbv for beagle C) showed strong agreement with the actual CONCAN values, with an ICC of 0.996 (P = 0.002) and Pearson’s r of 0.994 (P = 0.046). Conclusion The physiological dead space to tidal volume ratio from mixed air in beagles can be accurately measured using the existing time-volume and time-CO2 curves from the anesthesia machine, enabling corrections of exhaled propofol concentrations in mixed air samples.

Abstract Background Major abdominal surgery is a kind of high-risk surgery type for postoperative acute kidney injury (AKI) among non-cardiac surgeries. Despite dexmedetomidine exerts significant renal protective effects in cardiac surgeries and animal studies, whether it is associated with a lower incidence of AKI in major abdominal surgeries remains unclear. Methods From January 2019 to July 2021, patients undergoing elective major abdominal surgery in West China Hospital were enrolled. Participants were divided into two groups based on exposure to continuous intravenous dexmedetomidine: the Dex group (exposed) and the Control group (not exposed). The primary outcome was the incidence of AKI in the postoperative 7 days. Secondary outcomes included intraopertive average urine output, renal function on the first day after surgery, incidence of postoperative dialysis, postoperative intensive care unit (ICU) admission, in-hospital mortality, length of hospital stay, incidence of intraoperative hypotension and bradycardia, and intraoperative use of inotropes and vasopressors. Propensity score matching (PSM), based on participants’ baseline and intraoperative characteristics, was performed to minimize potential bias. Furthermore, a subgroup analysis was conducted based on the infusion rate and the use of a loading dose to explore the effects of different methods of dexmedetomidine administration on AKI. The subgroups included: loading dose, non-loading dose, low-infusion rate (infusion rate ≤ 0.4 µg/kg/h), and high-infusion rate (infusion rate > 0.4 µg/kg/h). Results After PSM with a ratio of 1:1, a total of 8836 patients were successfully matched. Dexmedetomidine administration had no association with the incidence of postoperative AKI, serum creatinine (Scr) level on the first postoperative day, incidence of postoperative dialysis, postoperative ICU admission, in-hospital mortality, length of hospital stay, intraoperative hypotension, or the use of inotropes and vasopressors, but had association with increased intraoperative average urine output (122.95 (76.80, 189.27) vs. 104.65 (67.04, 161.07) ml/h, P

Abstract Retinal microaneurysm (MA) is a definite earliest clinical sigh of diabetic retinopathy (DR). Its automatic segmentation is key to realizing intelligent screening for early DR, which can significantly reduce the risk of visual impairment in patients. However, the minute scale and subtle contrast of MAs against the background pose challenges for segmentation. This paper focuses on automatic MA segmentation in fundus images. A novel pyramid feature fusion network (PFFNet) that progressively develops and fuses rich contextual information by integrating two pyramid modules is proposed. Multiple global pyramid scene parsing (GPSP) modules are introduced between the encoder and decoder to provide diverse global contextual information for the decoder through reconstructing skip connections. Additionally, a spatial scale‐aware pyramid (SSAP) module is introduced to dynamically fuse multi‐scale contextual information. This rich contextual information will help to identify MAs from low‐contrast background. Furthermore, to mitigate issue related to category imbalance, a combo loss function is introduced. Finally, to validate the effectiveness of the proposed method, experiments are conducted on two publicly available datasets, IDRiD and DDR, and PFFNet is compared with several state‐of‐the‐art models. The experimental results demonstrate the superiority of our PFFNet in the MA segmentation task.

ABSTRACT This work takes the natural gas hydrate (NGH) reservoir in the Shenhu area at the South China Sea as the target. Using the quartz sand, calcite grains, and illite powder as the main mineral composites, and Portland cement as the bonding material, the host skeleton with similar porosity and mechanical properties to the target reservoir were prepared. Ice was used to simulate natural gas hydrates for their high similarity in mechanical properties and distributions within porous host. The ice saturation in the host skeleton is quantitatively controlled by the quality method. As an analogical simulation, artificial samples with different ice saturations were tested by uniaxial compression measurements and the Brazilian tensile tests, aiming to reveal the mechanical behavior of NGH sediments. The results indicated that the plasticity of the artificial sample increases and its damage form transitions from brittleness to ductility as the ice saturation increases. The effects of free water and ice on the strength of saturated samples are quite different. The free water tends to reduce the strength of the sample due to illite hydration and change of internal friction. The bonding effect of ice tends to increase the strength of the sample, while the ice could also reduce the internal friction. When the ice saturation is larger than 30%, the compressive and tensile strengths of the sample increase with ice saturation, which could be regressed as yc = 2.2628S + 0.8322, and yt = 0.411S + 0.0273, respectively. The constitutive model was developed based on the equivalent medium theory and the D‐P criterion, which could describe the experiment data well with deviations less than 10%.

While propofol can be detected in exhaled breath in rats, robust evidence supporting its correlation with plasma concentrations or its use in predicting plasma levels remains lacking. In this study, eighteen mechanically ventilated rats were divided into three groups and injected with low (Group BL, n = 6), medium (Group BM, n = 6), or high (Group BH, n = 6) doses of propofol. The propofol concentration in exhaled breath (Ce-pro) was determined online using vacuum ultraviolet time-of-flight mass spectrometry (VUV-TOF MS), while the propofol concentration in plasma (Cp-pro) were measured using high-performance liquid chromatograph. The results indicated that after propofol injection, the peak Ce-pro was 5.87 ± 1.67 ppbv, 16.54 ± 7.22 ppbv, and 25.40 ± 3.68 ppbv, respectively. Across the different dose groups, Cmax of Ce-pro and Cp-pro were linearly correlated (PBL = 0.032, PBM = 0.031, PBH = 0.049). Tmax of Ce-pro was 1.22 ± 0.17 min, 1.28 ± 0.13 min, and 1.33 ± 0.01 min, respectively (P = 0.341), similar to the Tmax of Cp-pro (1.00 ± 0.00 min). After natural logarithm transformation, the correlation between LN(Ce-pro) and LN(Cp-pro) was well fitted by a linear model, with RBL2 = 0.94, RBM2 = 0.95, RBH2 = 0.98, and RALL2 = 0.96. Using the obtained regression equation LN(Cp-pro) = 1.42*LN(Ce-pro)-1.70, the predicted Cp-pro values showed excellent agreement with the actual values within groups (ICCBL = 0.92; ICCBM = 0.97, ICCBH = 0.99, all P < 0.001). This study demonstrates a strong correlation between exhaled and plasma propofol concentrations in rats, indicating that exhaled concentrations can be effectively used to estimate plasma levels.

Abstract Age-related macular degeneration (AMD) and diabetic macular edema (DME) are significant causes of blindness worldwide. The prevalence of these diseases is steadily increasing due to population aging. Therefore, early diagnosis and prevention are crucial for effective treatment. Classification of Macular Degeneration OCT Images is a widely used method for assessing retinal lesions. However, there are two main challenges in OCT image classification: incomplete image feature extraction and lack of prominence in important positional features. To address these challenges, we proposed a deep learning neural network model called MSA-Net, which incorporates our proposed multi-scale architecture and spatial attention mechanism. Our multi-scale architecture is based on depthwise separable convolution, which ensures comprehensive feature extraction from multiple scales while minimizing the growth of model parameters. The spatial attention mechanism is aim to highlight the important positional features in the images, which emphasizes the representation of macular region features in OCT images. We test MSA-NET on the NEH dataset and the UCSD dataset, performing three-class (CNV, DURSEN, and NORMAL) and four-class (CNV, DURSEN, DME, and NORMAL) classification tasks. On the NEH dataset, the accuracy, sensitivity, and specificity are 98.1%, 97.9%, and 98.0%, respectively. After fine-tuning on the UCSD dataset, the accuracy, sensitivity, and specificity are 96.7%, 96.7%, and 98.9%, respectively. Experimental results demonstrate the excellent classification performance and generalization ability of our model compared to previous models and recent well-known OCT classification models, establishing it as a highly competitive intelligence classification approach in the field of macular degeneration.

AimsWe aim to explore the predictive value of admission blood glucose to serum albumin ratio (AAR) for futile recanalization after successful interventional recanalization of acute cerebral infarction.MethodsWe retrospectively collected the data of patients suffered from acute cerebral infarction due to anterior circulation large vessel occlusion and received successful interventional recanalization from January 2019 to November 2023. Statistical analysis of clinical data was conducted using SPSS 26.0.ResultsA total of 452 patients were included in the study. There were statistically significant differences in mRS score and futile recanalization rates among the three groups of patients at 3 months after surgery according to AAR tertile. In the multiple logistic regression analysis, there were statistically significant differences in Diabetes, grade of NIHSS score at admission, AAR tertiles, good collateral circulation and Pathogenesis. The Receiver Operating Characteristic curve (ROC) curve of AAR predicting futile recanalization was drawn with an AUC of 0.582 and a 95% confidence interval of 0.529–0.634. After combining grade of NIHSS score at admission, AAR tertiles and good collateral circulation, a ROC curve was drawn to predict futile recanalization, with an AUC of 0.907 and a 95% confidence interval of 0.879–0.936.ConclusionAAR is a new composite indicator for predicting futile recanalization in patients with acute cerebral infarction with anterior circulation large vessel occlusion. The combination of grade of NIHSS score at admission, AAR tertiles and good collateral circulation has a high predictive power for futile recanalization.

Propofol, a widely used intravenous anesthetic agent, requires accurate monitoring to ensure therapeutic efficacy and prevent oversedation. Recent developments in modern analytical instrumentation have led to significant breakthroughs in on-line analysis of exhaled breath. This review discusses several sophisticated analytical methods that have been explored for noninvasive, real-time monitoring of propofol concentrations, including proton transfer reaction mass spectrometry, selected ion flow tube mass spectrometry, ion mobility spectrometry, and gas chromatography coupled to surface acoustic wave sensors. These techniques have demonstrated good correlations between plasma and exhaled propofol concentrations and between exhaled propofol concentrations and its cerebral effects. Despite these advances, the use of these technologies in clinical settings is hampered by challenges such as equipment noise, bulkiness, and high cost, as well as limitations related to endotracheal intubation, strong adsorption of propofol to components of the respiratory circuit, variability in respiratory patterns, susceptibility to changes in pulmonary ventilation and blood flow, inconsistencies in calibration methods, and the influence of other drugs and temperature fluctuations on measurement accuracy. Overcoming these technical and procedural challenges is critical to advancing the clinical application of breath analysis for propofol monitoring. This article reviews published studies and summarizes the progress and ongoing challenges in the field.

BackgroundPostoperative pneumonia, a prevalent form of hospital-acquired pneumonia, poses significant risks to patients’ prognosis and even their lives. This study aimed to develop and validate a predictive model for postoperative pneumonia in surgical patients using nine machine learning methods.ObjectiveOur study aims to develop and validate a predictive model for POP in surgical patients using nine machine learning algorithms. By evaluating the performance differences among these machine learning models, this study aims to assist clinicians in early prediction and diagnosis of POP, providing optimal interventions and treatments.MethodsRetrospective data from electronic medical records was collected for 264 patients diagnosed with postoperative pneumonia and 264 healthy control surgical patients. Through correlation screening, chi-square tests, and feature importance ranking, 47 variables were narrowed down to 5 potential predictive factors based on the main cohort of 528 patients. Nine machine learning models, including k-nearest neighbors, support vector machine, random forest, decision tree, gradient boosting machine, adaptive boosting, naive bayes, general linear model, and linear discriminant analysis, were developed and validated to predict postoperative pneumonia. Model performance was evaluated using the area under the receiver operating curve, sensitivity, specificity, accuracy, precision, recall, and F1 score. A distribution plot of feature importance and feature interaction was obtained to interpret the machine learning models.ResultsAmong 17,190 surgical patients, 264 (1.54%) experienced postoperative pneumonia, which resulted in adverse outcomes such as prolonged hospital stay, increased ICU admission rates, and mortality. We successfully established nine machine learning models for predicting postoperative pneumonia in surgical patients, with the general linear model demonstrating the best overall performance. The AUC of the general linear model on the testing set was 0.877, with an accuracy of 0.82, specificity of 0.89, sensitivity of 0.74, precision of 0.88, and F1 score of 0.80. Our study revealed that the duration of bed rest, unplanned re-operation, end-tidal CO2, postoperative albumin, and chest X-ray film were significant predictors of postoperative pneumonia.ConclusionOur study firstly demonstrated that the general linear model based on 5 common variables might predict postoperative pneumonia in the general surgical population.

IntroductionThe extent to which sinks are contaminated by carbapenem-resistant Acinetobacter baumannii (CRAB) in intensive care units (ICUs) and the association between these contaminated sinks and hospital-acquired CRAB infections during the non-cluster period remains largely unknown. Here, we performed a prospective multicenter study in 16 ICUs at 11 tertiary hospitals in Chengdu, China.MethodsWe sampled sinks, collected CRAB clinical isolates, and conducted whole-genome sequencing and analysis.ResultsA total of 789 swabs were collected from 158 sinks, and 16 CRAB isolates were recovered from 16 sinks, resulting in a contamination rate of 10.16%. Twenty-seven clinical isolates were collected during the study period. The majority (97.67%, 42/43) of the CRAB isolates belonged to ST2, and 36 (83.72%) of them had both blaOXA-23 and blaOXA-66. The 43 strains belonged to 12 clones. One certain clone caused multiple contaminations of seven sinks in one GICU. Two clones of ST2 blaOXA-23 and blaOXA-66-carrying sink strains were likely the sources of the two clusters in the two GICUs, respectively. Five ST2 blaOXA-23-carrying isolates were found to be common clones but were recovered from two hospitals.ConclusionThe contamination rate of CRAB in handwashing sinks is high in some local ICUs, and the contaminated sinks can serve as environmental reservoirs for CRAB clusters.

Objectives: For prostate cancer (PCa), hundreds of risk variants have been identified. It remains unknown whether the polygenic risk score (PRS) that combines the effects of these variants is also a sufficiently informative metric with relevance to the molecular mechanisms of carcinogenesis in prostate. We aimed to understand the biological basis of PRS and racial disparities in the cancer. Methods: We performed a comprehensive analysis of the data generated (deposited in) by several genomic and/or transcriptomic projects (databases), including the GTEx, TCGA, 1000 Genomes, GEO and dbGap. PRS was constructed from 260 PCa risk variants that were identified by a recent trans-ancestry meta-analysis and contained in the GTEx dataset. The dosages of risk variants and the multi-ancestry effects on PCa incidence estimated by the meta-analysis were used in calculating individual PRS values. Results: The following novel results were obtained from our analyses. (1) In normal prostate samples from healthy European Americans (EAs), the expression levels of 540 genes (termed PRS genes) were associated with the PRS ( P

Abstract Objective To explore the imaging and transcranial Doppler cerebral blood flow characteristics of cerebrovascular fenestration malformation and its relationship with the occurrence of ischemic cerebrovascular disease. Methods A retrospective analysis was conducted on the imaging data of 194 patients with cerebrovascular fenestration malformation who visited the Heyuan People’s Hospital from July 2021 to July 2023. The location and morphology of the fenestration malformation blood vessels as well as the presence of other cerebrovascular diseases were analyzed. Transcranial Doppler cerebral blood flow detection data of patients with cerebral infarction and those with basilar artery fenestration malformation were also analyzed. Results A total of 194 patients with cerebral vascular fenestration malformation were found. Among the artery fenestration malformation, basilar artery fenestration was the most common, accounting for 46.08% (94/194). 61 patients (31.44%) had other vascular malformations, 97 patients (50%) had cerebral infarction, of which 30 were cerebral infarction in the fenestrated artery supply area. 28 patients with cerebral infarction in the fenestrated artery supply area received standardized antiplatelet, lipid-lowering and plaque-stabilizing medication treatment. During the follow-up period, these patients did not experience any symptoms of cerebral infarction or transient ischemic attack again. There were no differences in peak systolic flow velocity and end diastolic flow velocity, pulsatility index and resistance index between the ischemic stroke group and the no ischemic stroke group in patients with basal artery fenestration malformation (P > 0.05). Conclusion Cerebrovascular fenestration malformation is most common in the basilar artery. Cerebrovascular fenestration malformation may also be associated with other cerebrovascular malformations. Standardized antiplatelet and statin lipid-lowering and plaque-stabilizing drugs are suitable for patients with cerebral infarction complicated with fenestration malformation. The relationship between cerebral blood flow changes in basilar artery fenestration malformation and the occurrence of ischemic stroke may not be significant.

Abstract Redundancy elimination techniques are extensively investigated to reduce storage overheads for cloud‐assisted health systems. Deduplication eliminates the redundancy of duplicate blocks by storing one physical instance referenced by multiple duplicates. Delta compression is usually regarded as a complementary technique to deduplication to further remove the redundancy of similar blocks, but our observations indicate that this is disobedient when data have sparse duplicate blocks. In addition, there are many overlapped deltas in the resemblance detection process of post‐deduplication delta compression, which hinders the efficiency of delta compression and the index phase of resemblance detection inquires abundant non‐similar blocks, resulting in inefficient system throughput. Therefore, a multi‐feature‐based redundancy elimination scheme, called MFRE, is proposed to solve these problems. The similarity feature and temporal locality feature are excavated to assist redundancy elimination where the similarity feature well expresses the duplicate attribute. Then, similarity‐based dynamic post‐deduplication delta compression and temporal locality‐based dynamic delta compression discover more similar base blocks to minimise overlapped deltas and improve compression ratios. Moreover, the clustering method based on block‐relationship and the feature index strategy based on bloom filters reduce IO overheads and improve system throughput. Experiments demonstrate that the proposed method, compared to the state‐of‐the‐art method, improves the compression ratio and system throughput by 9.68% and 50%, respectively.

In order to improve the production of coalbed methane vertical wells in the central and northern Zhengzhuang block, southern Qinshui Basin, Shanxi, China, this paper analyzes the reasons for the poor stimulation effect of medium-deep coalbed methane vertical wells, based on the ground stress test data and fracturing monitoring data of these evaluation wells in the study area, proposes targeted stimulation techniques, designs and carries out field comparative pilot studies and analyzes their results. The results show that there are three main reasons for the low production of these vertical wells in the study area. Firstly, the vertical fracture is dominant, resulting in the shorter length of hydraulic fractures. With the increase of burial depth, the length and width of fractures decreases at the same fracturing scale. Secondly, with the increase of burial depth, the embedment depth of proppants into coal rock increases and the closure of hydraulic fractures speeds up. As a result, the stable production time is short, and the main form of gas production curve is “single peak” type. Thirdly, after the initial fracturing, the coal body structure is much more broken, and new fractures are easy to enter the initial fractures, which increases the difficulty of creating new fractures, resulting in poor stimulation effect. In view of the above reasons, the paper proposes an innovative technology of pre-plug, large-scale and remote-support re-fracturing. Pre-plug means that relatively low displacement, sand ratio and scale are first used to fill initial fractures, and then large-scale re-fracturing is carried out to create new fractures. Large-scale fracturing refers to the fracturing with large displacement, large fluid volume and high sand ratio. In order to improve the stimulation effect of middle-deep reservoirs, the fracturing fluid volume is increased from 600−800 m3 to more than 1 300−2 000 m3, the displacement is increased from 6−8 m3/min to more than 10−14 m3/min, and a low viscosity fracturing fluid system combined with low density proppants is used to increase the sand ratio from 7%−8% to more than 10%−15%. Remote-support is a combination of self-suspended proppants and large displacement to increase proppants migration distance and increase the proportion of the propped fractures. The average daily production of a single well reached 1 380 m3, which was 1 190 m3 higher than that before, and nearly 1 000 m3 higher than the stable gas production of adjacent wells, realizing the production breakthrough of vertical wells in the low-production area of the middle-deep reservoir in the north of Zhengzhuang block. Results of the comparative pilot studies showed that the average net construction pressure increased by 3.3 MPa after pre-plug, compared with the initial fracturing, which means that new fractures were formed and resulted in the production increase by 1 000 m3 compared with that of the wells without the Pre-plug. The pilot results show that, in general, the larger the technical parameters of pre-plug, large-scale and remote-support re-fracturing, the better the production performance.

Abstract Senescent cancer cells are endowed with high immunogenic potential that has been leveraged to elicit antitumor immunity and potentially complement anticancer therapies. However, the efficacy of live senescent cancer cell‐based vaccination is limited by interference from immunosuppressive senescence‐associated secretory phenotype and pro‐tumorigenic capacity of senescent cells. Here, a senescent cancer cell‐based nanovaccine with strong immunogenicity and favorable potential for immunotherapy is reported. The biomimetic nanovaccine integrating a senescent cancer cell membrane‐coated nanoadjuvant outperforms living senescent cancer cells in enhancing dendritic cells (DCs) internalization, improving lymph node targeting, and enhancing immune responses. In contrast to nanovaccines generated from immunogenic cell death‐induced tumor cells, senescent nanovaccines facilitate DC maturation, eliciting superior antitumor protection and improving therapeutic outcomes in melanoma‐challenged mice with fewer side effects when combined with αPD‐1. The study suggests a versatile biomanufacturing approach to maximize immunogenic potential and minimize adverse effects of senescent cancer cell‐based vaccination and advances the design of biomimetic nanovaccines for cancer immunotherapy.

Abstract Embryonic stem cells (ESCs) exhibit unique attributes of boundless self-renewal and pluripotency, making them invaluable for fundamental investigations and clinical endeavors. Previous examinations of microgravity effects on ESC self-renewal and differentiation have predominantly maintained a descriptive nature, constrained by limited experimental opportunities and techniques. In this investigation, we present compelling evidence derived from murine and human ESCs, demonstrating that simulated microgravity (SMG)-induced stress significantly impacts self-renewal and pluripotency through a previously unidentified conserved mechanism. Specifically, SMG induces the upregulation of heat shock protein genes, subsequently enhancing the expression of core pluripotency factors and activating the Wnt and/or LIF/STAT3 signaling pathways, thereby fostering ESC self-renewal. Notably, heightened Wnt pathway activity, facilitated by Tbx3 upregulation, prompts mesoendodermal differentiation in both murine and human ESCs under SMG conditions. Recognizing potential disparities between terrestrial SMG simulations and authentic microgravity, forthcoming space flight experiments are imperative to validate the impact of reduced gravity on ESC self-renewal and differentiation mechanisms.

We established a new conjugate gradient method with an efficient restart direction for solving large scale unconstrained optimization problems. The modified method was proposed under the Polak-Ribière-Polyak conjugate gradient method. Under the strong Wolfe line search, the search direction of the new method was sufficiently descent and its global convergence property could be proved. Compared with other methods having good numerical performances, numerical experiments and image restorations showed that the modified method was more effective.

Abstract Purposes The aim of this study was to construct a lateral classification system for nontraumatic osteonecrosis of femoral head (NONFH) through three-dimensional reconstruction of the necrotic area to assist in evaluating the prognosis of patients with JIC type C1. Methods Retrospective analysis of patients with JIC type C1 NONFH from January 2018 to December 2020. All patients were followed up for more than 3.5 years. The patients were divided into collapse group and non-collapse group according to whether the femoral head collapsed during the follow-up.Lateral classification system for femoral head necrosis is constructed through three-dimensional reconstruction of the necrotic area.Comparison of lateral classification system,midsagittal necrosis angle(MNA)and general data between the two groups.Furthermore, ROC curve analysis and survival analysis were performed. Results 318 patients were included in this study.There was a significant difference between the two groups in the lateral classification system (P

Abstract. Background:. Postoperative pulmonary complications often lead to increased mortality and financial burden. Residual paralysis plays a critical role in postoperative pulmonary complications. This meta-analysis was performed to determine whether sugammadex overmatches neostigmine in reducing postoperative pulmonary complications. Methods:. PubMed, Embase, Web of Science, Medline through Ovid, Cochrane Library, Wanfang, China National Knowledge Infrastructure, and Chinese BioMedical Literature Databases were searched from their inception to 24 June, 2021. Random effects models were used for all analyses. Cochrane risk of bias tool was used to assess the quality of RCTs, while Newcastle Ottawa Quality Assessment Scale was used to assess for the quality of cohort studies. Results:. Seventeen studies were included in the meta-analysis. Pooled data from cohort studies showed reversing neuromuscular blocking with sugammadex had less risk of compound postoperative pulmonary complications (relative risk [RR]: 0.73; 95% confidence interval [CI]: 0.60–0.89; P = 0.002; I2 = 81%), pneumonia (RR: 0.64; 95% CI: 0.48–0.86; I2 = 42%) and respiratory failure (RR: 0.48; 95% CI: 0.41–0.56; I2 = 0%). However, pooled data from RCTs did not show any difference between the two groups in pneumonia (RR: 0.58; 95% CI: 0.24–1.40; I2 = 0%) and no respiratory failure was reported in the included RCTs. The difference was not found between sugammadex and neostigmine about atelectasis in pooled data from either RCTs (RR: 0.85; 95% CI: 0.69–1.05; I2 = 0%) or cohort studies (RR: 1.01; 95% CI: 0.87–1.18; I2 = 0%). Conclusion:. The evidence of superiority of sugammadex was limited by the confounding factors in cohort studies and small scale of RCTs. Whether sugammadex precedes neostigmine in preventing pulmonary complications after surgery is still unknown. Well-designed RCTs with large scale are needed. Registration:. PROSPERO (https://www.crd.york.ac.uk/PROSPERO/); CRD 42020191575

This work analyses interaction factors affecting the preparation of a geopolymer from coal gangue and establishes an accurate mechanical prediction model to efficiently predict the flexural and compressive strength. Coal gangue is the main raw material, and NaOH and water glass are chosen as the activators to synthesise the geopolymer. First, response Surface Methodology (RSM) was applied to analyse the interaction impacts of the water glass modulus, liquid-to-solid ratio, sodium silicate/coal gangue ratio, and curing temperature on the mechanical properties. After that, a modified Support Vector Machine (SVM) and RSM were applied to establish a mechanical prediction model. The results reveal that there are two key interaction factors for the geopolymer properties. First, the water glass modulus and liquid-to-solid ratio could jointly affect the flexural strength. At the same time, the compressive strength is simultaneously influenced by the water glass modulus and curing temperature. Moreover, the analysis of the mechanical prediction models indicates that both the RSM and modified SVM could use little experimental data to predict the mechanical properties of geopolymer. However, the modified SVM has better prediction accuracy. Therefore, this study could efficiently predict the mechanical strength of a coal gangue-based geopolymer, conserve energy, and decrease the environmental pollution resulting from coal gangue.

The dried roots of Scutellaria baicalensis (S. baicalensis) have been widely used as a traditional medicine. Recently, climate change and human activities have caused the degeneration of its wildlife habitat. However, there is rare knowledge on the effect and interactive effect of different variables on the spatial heterogeneity of S. baicalensis and how the pattern of suitable cultivation area in China would shift in response to climate change. Based on the Geodetector and Habitat Suitability Index (HSI) method, we proposed an assessment model to identify the critical environmental variable(s) affecting the distribution of suitable cultivation area for S. baicalensis in China and to project its shift under climate change. The results showed that soil and mean annual temperature are two determining variables in its spatial heterogeneity in China. Compared to 1981–2010, future climate change may result in a decrease in its suitable area, and yet may result in an increase in the extremely suitable area (about 1.00–1.35 million km2). S. baicalensis in the southern and northwestern part of its current distribution and the southwestern part and small area of northern China may experience expansion during the 21st century, while S. baicalensis in southern China, the Huang-Huai-Hai plain, and the midwest of northwestern China may experience contractions. Meanwhile, climate warming is expected to shift its distribution northwest through an expansion at the northern (at least 84 km) and western (at least 62 km) boundary and contraction at the southern (at least 529 km) boundary, respectively. These results could provide valuable information to policy-makers for the conservation and scientific introduction of S. baicalensis.

El Niño-Southern Oscillation (ENSO), a cyclic climate phenomenon spanning interannual and decadal timescales, exerts substantial impacts on the global weather patterns and ecosystems. Recently, deep learning has brought considerable advances in the accurate prediction of ENSO occurrence. However, the current models are insufficient to characterize the evolutionary behavior of the ENSO, particularly lacking comprehensive modeling of local-range and longrange spatiotemporal interdependencies, and the incorporation of calendar monthly and seasonal properties. To make up this gap, we propose a Two-Stage SpatioTemporal (TSST) autoregressive model that couples the meteorological factor prediction with ENSO indicator prediction. The first stage predicts the meteorological time series by leveraging self-attention ConvLSTM network which captures both the local and the global spatial-temporal dependencies. The temporal embeddings of calendar months and seasonal information are further incorporated to preserves repeatedly-occurring-yet-hidden patterns in meteorological series. The second stage uses multiple layers to extract higher level of features from predicted meteorological factors progressively to generate ENSO indicators. The results demonstrate that our model outperforms the state-of-the-art ENSO prediction models, effectively predicting ENSO up to 24 months and mitigating the spring predictability barrier.

Abstract Phosphodiesterase type 5 inhibitors (PDE5is) constitute the primary therapeutic option for treating erectile dysfunction (ED). Nevertheless, a substantial proportion of patients, approximately 30%, do not respond to PDE5i treatment. Therefore, new treatment methods are needed. In this study, we identified a pathway that contributes to male erectile function. We show that mechano-regulated YAP/TAZ signaling in smooth muscle cells (SMCs) upregulates adrenomedullin transcription, which relaxed the SMCs to maintain erection. Using single-nucleus RNA sequencing, we investigated how penile erection stretches the SMCs, inducing YAP/TAZ activity. Subsequently, we demonstrate that YAP/TAZ plays a role in erectile function and penile rehabilitation, using genetic lesions and various animal models. This mechanism relies on direct transcriptional regulation of adrenomedullin by YAP/TAZ, which in turn modulates penile smooth muscle contraction. Importantly, conventional PDE5i, which targets NO-cGMP signaling, does not promote erectile function in YAP/TAZ-deficient ED model mice. In contrast, by activating the YAP/TAZ-adrenomedullin cascade, mechanostimulation improves erectile function in PDE5i nonrespondent ED model rats and mice. Furthermore, using clinical retrospective observational data, we found that mechanostimulation significantly promotes erectile function in patients irrespective of PDE5i use. Our studies lay the groundwork for exploring the mechano-YAP/TAZ-adrenomedullin axis as a potential target in the treatment of ED.

Abstract Background Aberrant epigenetic remodeling events contribute to progression and metastasis of breast cancer (Bca). The specific mechanims that epigenetic factors rely on to mediate tumor aggressiveness remain unclear. We aimed to elucidate the roles of epigenetic protein PHF6 in breast tumorigenesis. Methods Published datasets and tissue samples with PHF6 staining were used to investigate the clinical relevance of PHF6 in Bca. CCK-8, clony formation assays were used to assess cell growth capacity. Cell migration and invasion abilities were measured by Transwell assay. The gene mRNA and protein levels were measured by quantitative real-time PCR and western blot. Chromatin immunoprecipitation (ChIP)-qPCR assays were used to investigate transcriptional relationships among genes. The Co-immunoprecipitation (Co-IP) assay was used to validate interactions between proteins. The CRISPR/Cas9 editing technology was used to construct double HIF knockout (HIF-DKO) cells. The subcutaneous xenograft model and orthotopic implantation tumor model were used to asess in vivo tumor growth. Results In this study, we utilized MTT assay to screen that PHF6 is required for Bca growth. PHF6 promotes Bca proliferation and migration. By analyzing The Cancer Genome Atlas breast cancer (TCGA-Bca) cohort, we found that PHF6 was significantly higher in tumor versus normal tissues. Mechanistically, PHF6 physically interacts with HIF-1α and HIF-2α to potentiate HIF-driven transcriptional events to initiate breast tumorigenesis. HIF-DKO abolished PHF6-mediated breast tumor growth, and PHF6 deficiency in turn impaired HIF transcriptional effects. Besides, hypoxia could also rely on YAP activation, but not HIF, to sustain PHF6 expressions in Bca cells. In addition, PHF6 recuits BPTF to mediate epigenetic remodeling to augment HIF transcriptional activity. Targeting PHF6 or BPTF inhibitor (AU1) is effective in mice models. Lastly, PHF6 correlated with HIF target gene expression in human breast tumors, which is an independent prognostic regulator. Conclusions Collectively, this study identified PHF6 as a prognostic epigenetic regulator for Bca, functioning as a HIF coactivator. The fundamental mechanisms underlying YAP/PHF6/HIF axis in breast tumors endowed novel epigenegtic targets for Bca treatment.

Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant which mainly exposed though diet. High-fat diet (HFD) can induce atherosclerosis, as can BaP. Unhealthy dietary habits lead to high intake of both BaP and lipids. However, the combined effect of BaP and HFD on atherosclerosis and lipid accumulation in the arterial wall, the initial stage of atherosclerosis, is unclear. In this study, C57BL/6 J mice were subchronically exposed to BaP and a HFD, and the mechanism of lipid accumulation was investigated in EA.hy926 and HEK293 cells. Results showed that BaP and HFD increased blood lipids and damaged aortic wall synergistically. Meanwhile, LDL enhanced the toxicity of BaP, and BaP promoted the production of reactive oxygen species and malonaldehyde in EA.hy926 cells, which aggravated LDL-induced cell injury. Moreover, BaP and HFD/LDL induced LDL accumulation in the aortic wall of C57BL/6 J mice/EA.hy926, and the mechanism was by activating AHR/ARNT heterodimer to combine with the scavenger receptor BⅠ (SR-BⅠ) and activin receptor-like kinase 1 (ALK1) promoter regions to transcriptional upregulate its expression, which enhanced the uptake of LDL, and promoting the production of AGEs to inhibit reverse cholesterol transport by SR-BI. BaP and lipid synergistically promoted aortic and endothelial damage, and the health risk of their combined intake should be paid attention to.

Abstract Background Spinal cord infarction is a rare disorder, constituting only 1% to 2% of all neurological vascular emergencies (making it less frequent than ischaemic brain injury); however, it is severe. A case of long-segment spinal cord infarction complicated with multiple cerebral infarctions has not been reported to date. Case presentation Here, we describe one such case: a patient with spinal cord infarction from the cervical 7 (C7) to thoracic 6 (T6) vertebrae, along with anterior spinal artery syndrome and complicated by multiple cerebral infarctions. A 65-year-old farmer experienced sudden onset of severe pain in his chest, back and upper limbs while unloading heavy objects. Subsequently, both his lower limbs became weak and hypoaesthetic, and he was unable to walk. Spinal magnetic resonance imaging (MRI) revealed equal T1 and long T2 signals centred on the anterior horn of the spinal cord. The axial slice of these signals was shaped like an owl’s eye. After receiving drug treatment and active rehabilitation treatment, the patient’s ability to walk was restored. Conclusions Long-segment spinal cord infarction is rare and can be complicated with cerebral infarction. The specific aetiology is worth exploring.

Abstract The frozen section (FS) diagnoses of pathology experts are used in China to determine whether sentinel lymph nodes of breast cancer have metastasis during operation. Direct implementation of a deep neural network (DNN) in clinical practice may be hindered by misdiagnosis of the algorithm, which affects a patient's treatment decision. In this study, we first obtained the prediction result of the commonly used patch-DNN, then we present a relative risk classification and regression tree (RRCART) to identify the misdiagnosed whole-slide images (WSIs) and recommend them to be reviewed by pathologists. Applying this framework to 2362 WSIs of breast cancer lymph node metastasis, test on frozen section results in the mean area under the curve (AUC) reached 0.9851. However, the mean misdiagnosis rate (0.0248), was significantly higher than the pathologists’ misdiagnosis rate (p 0.01). However, the other low-accuracy group included most of the misdiagnoses of DNN models. Our research shows that the misdiagnosis from deep learning model can be further enriched by our method, and that the low-accuracy WSIs must be selected for pathologists to review and the high-accuracy ones may be ready for pathologists to give diagnostic reports.

Abstract This paper addresses the adaptive control problem for a one‐link manipulator system driven by a motor with uncertain virtual control coefficients (VCCs) and nonlinearities. The unknown VCCs are composed by the certain and uncertain items, where the first part is decided by the moment of inertia of the manipulator and another is generated by that of the load. An auxiliary variable and the Nussbaum gain technique are invoked to handle the uncertainties of VCCs and input nonlinearities. Moreover, a finite‐time prescribed performance function is introduced to design the adaptive control scheme for the manipulator system, which guarantees the tracking error converges to a fixed interval in a setting time and all signals in the manipulator system are bounded.

Identification of slope subsurface strata for natural soil slopes is essential to assess the stability of potential landslides. The highly variable strata in a slope are hard to characterize by traditional boreholes at limited locations. Ground-penetrating radar (GPR) is a non-destructive method that is capable of capturing continuous subsurface information. However, the accuracy of subsurface identification using GPRs is still an open issue. This work systematically investigates the capability of the GPR technique to identify different strata via both laboratory experiments and on-site examination. Six large-scale models were constructed with various stratigraphic interfaces (i.e., sand–rock, clay–rock, clay–sand, interbedded clay, water table, and V–shaped sand–rock). The continuous interfaces of the strata in these models were obtained using a GPR, and the depths at different points of the interfaces were interpreted. The interpreted depths along the interface were compared with the measured values to quantify the interpretation accuracy. Results show that the depths of interfaces should be interpreted with the relative permittivity, back-calculated using on-site borehole information instead of empirical values. The relative errors of the depth of horizontal interfaces of different strata range within ±5%. The relative and absolute errors of the V–shaped sand–rock interface depths are in the ranges of [−9.9%, 10.5%] and [−107, 119] mm, respectively. Finally, the GPR technique was used in the field to identify the strata of a slope from Tanglang Mountain in China. The continuous profile of the subsurface strata was successfully identified with a relative error within ±5%.

The spectrum situation awareness problem in space–air–ground integrated networks (SAGINs) is studied from a tensor-computing perspective. Tensor and tensor computing, including tensor decomposition, tensor completion and tensor eigenvalues, can satisfy the application requirements of SAGINs. Tensors can effectively handle multidimensional heterogeneous big data generated by SAGINs. Tensor computing is used to process the big data, with tensor decomposition being used for dimensionality reduction to reduce storage space, and tensor completion utilized for numeric supplementation to overcome the missing data problem. Notably, tensor eigenvalues are used to indicate the intrinsic correlations within the big data. A tensor data model is designed for space–air–ground integrated networks from multiple dimensions. Based on the multidimensional tensor data model, a novel tensor-computing-based spectrum situation awareness scheme is proposed. Two tensor eigenvalue calculation algorithms are studied to generate tensor eigenvalues. The distribution characteristics of tensor eigenvalues are used to design spectrum sensing schemes with hypothesis tests. The main advantage of this algorithm based on tensor eigenvalue distributions is that the statistics of spectrum situation awareness can be completely characterized by tensor eigenvalues. The feasibility of spectrum situation awareness based on tensor eigenvalues is evaluated by simulation results. The new application paradigm of tensor eigenvalue provides a novel direction for practical applications of tensor theory.

Abstract For prostate cancer (PCa) patients, biochemical recurrence (BCR) is the first sign of disease relapse and the subsequent metastasis. TP53 mutations are relatively prevalent in advanced PCa forms. We aimed to utilize this knowledge to identify robust transcriptomic signatures for BCR prediction in patients with Gleason score ≥ 7 cancers, which cause most PCa deaths. Using the TCGA-PRAD dataset and the novel data-driven stochastic approach proposed in this study, we identified a 25-gene signature from the genes whose expression in tumors was associated with TP53 mutation statuses. The predictive strength of the signature was assessed by AUC and Fisher’s exact test p-value according to the output of support vector machine-based cross validation. For the TCGA-PRAD dataset, the AUC and p-value were 0.837 and 5 × 10–13, respectively. For five external datasets, the AUCs and p-values ranged from 0.632 to 0.794 and 6 × 10–2 to 5 × 10–5, respectively. The signature also performed well in predicting relapse-free survival (RFS). The signature-based transcriptomic risk scores (TRS) explained 28.2% of variation in RFS on average. The combination of TRS and clinicopathologic prognostic factors explained 23–72% of variation in RFS, with a median of 54.5%. Our method and findings are useful for developing new prognostic tools in PCa and other cancers.

(+)-Catechin (CE) is mainly found in green and black tea and has many biological effects, such as anti-inflammatory, anti-cancer, anti-viral effects, protecting human organs, especially the kidney. This study aims to identify the circRNAs induced by CE in db/db mice and their roles in diabetic nephropathy progression. After the db/db mice were treated with CE, RNA-seq was performed to identify the differentially expressed circRNA and mRNAs. The ceRNA regulatory network was constructed and analyzed using bioinformatics software and public databases (Cytoscape, ClueGO, MiRWalk, STRING, et al.). Our results revealed that 6 differentially expressed circRNAs are most associated with the cholinergic synapse, neurotrophin signaling pathway, and insulin signaling pathway. Among these, circRNA.5549 and circRNA.4712 might regulate Cd36, Cyp26b1, C8a, Cyp2j13, Grem2 genes through ceRNA regulatory mechanism in the presence of CE treatment. The expanded network of proteins interacting with these 5 genes shows that the TGF-β signaling pathway, signaling pathways regulating pluripotency of stem cell, fat digestion and absorption, and PPAR signaling pathway was highly enriched. Overall, circRNA.5549 and circRNA.4712 exhibit a promotive function in CE-treated db/db mice, especially in circRNA.5549/miR-29a-5P/Cd36 regulatory network, and this evidence suggest that their ceRNA regulatory network might be a therapeutic target for DN in humans.

Introduction: There are currently no published reports of hyperperfusion syndrome in the non responsible vascular area after mechanical thrombectomy for acute cerebral infarction with large vessel occlusion. Here, we report a case of hyperperfusion syndrome in the blood supply area of the right middle cerebral artery after mechanical thrombectomy for acute cerebral infarction after vertebral artery occlusion. Patient concerns: A 21-year-old woman developed left vertebral artery occlusion, for which she received mechanical thrombectomy and successful recanalization of her occluded cerebral vessel. Subsequently, the patient became extremely agitated, with high blood pressure and headache. Diagnosis: Two hours after the operation, bedside transcranial Doppler ultrasound examination found that the cerebral blood flow velocity of the M1 segment of the right middle cerebral artery was more than twice that of the left middle cerebral artery. Combined with the symptoms, signs and examination results of the patient, hyperperfusion syndrome in the blood supply area of the right middle cerebral artery was considered. Interventions: The patient was administered sedation, and her pressure and ventricular rate were strictly controlled. She was no longer agitated, and her headache was significantly relieved at 36 hours after the operation. Outcomes: On the 5th day after the operation, the blood flow velocity of her right middle cerebral artery decreased to normal level, and the patient recovered well. Conclusion: In this case, after mechanical thrombectomy, such patients with acute posterior circulation cerebral infarction can experience hyperperfusion syndrome in the non responsible vascular area of the anterior circulation. Bedside transcranial Doppler cerebral blood flow examination can identify the hyperperfusion state of cerebral vessels in a timely manner and effectively guide treatment.

Soil salinity and water deficit often occur concurrently, but understanding their combined effects on plants’ ion regulation is limited. With aim to identify if introducing drought with salinity alleviates salt stress’s ionic effects, Panicum antidotale – a halophytic grass- was grown in the presence of single and combined stressors, i.e., drought and salt (low and high). Regulation of cations and anions along with the antioxidant capacity and modifications in leaf anatomy were investigated. Results showed a combination of low salt and drought minimally affected plant (dry) mass by improving the selective ions absorption and nutrient use efficiencies. The lowest ratio for efficiency of photosystem II and carbon assimilation (ΦPSII/ΦCO2) suggested less generation of reactive oxygen species, which were probably detoxified with constitutively performing antioxidant enzymes. In contrast, the combination of high salinity and drought escalated the adverse effects caused due to individual stressors. The selective ion absorption increased, but the non-selective ions transport caused an ionic imbalance indicating the highest ratio of Na+/K+. Although the area of mesophyll increased, a reduction in epidermis (cell number and area) predicted a mechanical injury prone to water loss in these plants. The compromised activity of antioxidant enzymes also suggested treatment-induced oxidative damage. Yet, the synergistic interaction between high salinity and drought was not detrimental to the survival of P. antidotale. Therefore, we suggest planting this grass in habitats with harsh environmental conditions to meet the increasing fodder demands without compromising agricultural lands’ productivity.

The relevance of nongenetic factors to prostate cancer (PCa) has been elusive. We aimed to quantify the contributions of environmental factors to PCa and identify risk-related diet metrics and relevant racial disparities. We performed a unique analysis of the Diet History Questionnaire data of 41 830 European Americans (EAs) and 1282 African Americans (AAs) in the PLCO project. The independent variables in the regression models consisted of age at trial entry, race, family history of prostate cancer (PCa-fh), diabetes history, body mass index (BMI), lifestyle (smoking and coffee consumption), marital status, and a specific nutrient/food factor (X). P PCa-fh > diabetes ⩾ race > lifestyle ⩾marital-status ⩾BMI > X. We confirmed previous studies showing that (1) high protein and saturated fat levels in diet were related to increased PCa risk, (2) high-level supplementary selenium intake was harmful rather than beneficial for preventing PCa, and (3) supplementary vitamin B6 was beneficial for preventing benign PCa. We obtained the following novel findings: high-level organ meat intake was an independent predictor for increased aggressive PCa risk; supplementary iron, copper and magnesium increased benign PCa risk; and the AA diet was “healthy” in terms of the relatively lower protein and fat levels and was “unhealthy” in that it more commonly contained organ meat. In conclusion, we established a priority ranking among the contributing factors for PCa and identified several risk-related diet metrics and the racial disparities. Our findings suggested some new approaches to prevent PCa such as restriction of organ meat intake and supplementary microminerals.

Abstract Mechanotransduction sensing of tissue architecture and cellular microenvironment is a fundamental regulator of cell fate, including cancer. Meanwhile, long noncoding RNAs (lncRNAs) play multifunctions during cancer development and treatment. However, the link between lncRNAs and cellular mechanotransduction in the context of cancer progression has not yet been elucidated. In this study, using atomic force microscopy (AFM), we find that ionizing radiation reduces tumor stiffness. Ionizing radiation-induced lncRNA CRYBG3 can blunt YAP/TAZ activity through interference with mechanotransduction, resulting in the inhibition of cell proliferation, invasion, and metastasis of lung cancer cells. In vivo, we found that loss of lncRNA CRYBG3 could power the tumor initiation and metastasis ability, but this was abolished by concomitant deplete TAZ. At the molecular level, lncRNA CRYBG3 that in turn dysregulates F-actin organization, activates the LATS1/2 kinase, all in all resulting in YAP/TAZ nuclear exclusion. Our research proposes that lncRNA CRYBG3 is a mediator of radiotherapy through its control of cancer-tissue mechanotransduction and wiring YAP/TAZ activity to control tumor growth and metastasis.

Chromatin modification contributes to pluripotency maintenance in embryonic stem cells (ESCs). However, the related mechanisms remain obscure. Here, we show that Npac, a “reader” of histone H3 lysine 36 trimethylation (H3K36me3), is required to maintain mouse ESC (mESC) pluripotency since knockdown of Npac causes mESC differentiation. Depletion of Npac in mouse embryonic fibroblasts (MEFs) inhibits reprogramming efficiency. Furthermore, our chromatin immunoprecipitation followed by sequencing (ChIP-seq) results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs. Interestingly, we find that Npac interacts with positive transcription elongation factor b (p-TEFb), Ser2-phosphorylated RNA Pol II (RNA Pol II Ser2P), and Ser5-phosphorylated RNA Pol II (RNA Pol II Ser5P). Furthermore, depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rif1. Taken together, we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interacting with RNA Pol II Ser2P and Ser5P.

Compelling experimental evidence confirms that the robustness and longevity of mixed chimerism (MC) relies on the persistence and availability of donor-derived hematopoietic stem cell (HSC) niches in recipients. Based on our prior work in rodent vascularized composite allotransplantation (VCA) models, we hypothesize that the vascularized bone components in VCA bearing donor HSC niches, thus may provide a unique biologic opportunity to facilitate stable MC and transplant tolerance. In this study, by utilizing a series of rodent VCA models we demonstrated that donor HSC niches in the vascularized bone facilitate persistent multilineage hematopoietic chimerism in transplant recipients and promote donor-specific tolerance without harsh myeloablation. In addition, the transplanted donor HSC niches in VCA facilitated the donor HSC niches seeding to the recipient bone marrow compartment and contributed to the maintenance and homeostasis of stable MC. Moreover, this study provided evidences that chimeric thymus plays a role in MC-mediated transplant tolerance through a mechanism of thymic central deletion. Mechanistic insights from our study could lead to the use of vascularized donor bone with pre-engrafted HSC niches as a safe, complementary strategy to induce robust and stable MC-mediated tolerance in VCA or solid organ transplantation recipients.

Abstract Background Symptom phrase recognition is essential to improve the use of unstructured medical consultation corpora for the development of automated question answering systems. A majority of previous works typically require enough manually annotated training data or as complete a symptom dictionary as possible. However, when applied to real scenarios, they will face a dilemma due to the scarcity of the annotated textual resources and the diversity of the spoken language expressions. Methods In this paper, we propose a composition-driven method to recognize the symptom phrases from Chinese medical consultation corpora without any annotations. The basic idea is to directly learn models that capture the composition, i.e., the arrangement of the symptom components (semantic units of words). We introduce an automatic annotation strategy for the standard symptom phrases which are collected from multiple data sources. In particular, we combine the position information and the interaction scores between symptom components to characterize the symptom phrases. Equipped with such models, we are allowed to robustly extract symptom phrases that are not seen before. Results Without any manual annotations, our method achieves strong positive results on symptom phrase recognition tasks. Experiments also show that our method enjoys great potential with access to plenty of corpora. Conclusions Compositionality offers a feasible solution for extracting information from unstructured free text with scarce labels.

With the increase of problem dimensions, most solutions of existing many-objective optimization algorithms are non-dominant. Therefore, the selection of individuals and the retention of elite individuals are important. Existing algorithms cannot provide sufficient solution precision and guarantee the diversity and convergence of solution sets when solving practical many-objective industrial problems. Thus, this work proposes an improved many-objective pigeon-inspired optimization (ImMAPIO) algorithm with multiple selection strategies to solve many-objective optimization problems. Multiple selection strategies integrating hypervolume, knee point, and vector angles are utilized to increase selection pressure to the true Pareto Front. Thus, the accuracy, convergence, and diversity of solutions are improved. ImMAPIO is applied to the DTLZ and WFG test functions with four to fifteen objectives and compared against NSGA-III, GrEA, MOEA/D, RVEA, and many-objective Pigeon-inspired optimization algorithm. Experimental results indicate the superiority of ImMAPIO on these test functions.

Introduction: Cerebrovascular fenestration malformation is a rare congenital vascular variation. Cerebrovascular fenestration malformation rarely directly leads to cerebral infarction, and the mechanism of cerebral infarction is not clear. Cases of young patients with vertebral artery fenestration malformation who suffered from acute cerebral infarction of posterior circulation are rare and have not been reported widely. Patient concerns: A 36-year-old male patient, who had been in good health and without a family history of stroke, was admitted to our hospital with a 6-h history of dizziness and unstable walking. Diagnosis: Brain MR examination showed multiple irregular high signal lesions in the left thalamus, left occipital lobe and left cerebellum. Brain MR enhancement examination confirmed multiple cerebral infarction in left thalamus, left occipital lobe and left cerebellum. CT angiography of head and neck showed fenestration deformity of V2–V3 segment of left vertebral artery. Interventions: Considering that the patient was suffering from acute cerebral infarction of posterior circulation, he was treated with antiplatelet, lipid-lowering and plaque stabilization, etc. Outcomes: After receiving our treatment, the patient's symptoms were relieved. At 3 and 6 months after discharge, there was no dizziness, unstable walking, no acute cerebral infarction, which meant that the patient recovered well. Conclusion: In the absence of traditional risk factors and other evidence of cryptogenic stroke, the cerebral infarction in the blood supply area of fenestration malformation should be considered to be related to fenestration malformation, but its pathogenesis is not clear. Antiplatelet therapy, lipid-lowering and plaque stabilization, etc. are effective in prevention of new infarction for such patients.

Mouse embryonic stem cells (mESCs) possess the remarkable characteristics of unlimited self-renewal and pluripotency, which render them highly valuable for both fundamental research and clinical applications. A comprehensive understanding of the molecular mechanisms underlying mESC function is of the utmost importance. The Human Silence Hub (HUSH) complex, comprising FAM208A, MPP8, and periphilin, constitutes an epigenetic silencing complex involved in suppressing retroviruses and transposons during early embryonic development. However, its precise role in regulating mESC pluripotency and differentiation remains elusive. In this study, we generated homogenous miniIAA7-tagged Mpp8 mouse ES cell lines. Upon induction of MPP8 protein degradation, we observed the impaired proliferation and reduced colony formation ability of mESCs. Furthermore, this study unveils the involvement of MPP8 in regulating the activity of the LIF/STAT3 signaling pathway and Nanog expression in mESCs. Finally, we provide compelling evidence that degradation of the MPP8 protein impairs the differentiation of mESC.

Abstract Breast cancer is the most common cancer in women and its incidence rates are rapidly increasing in China. Understanding the molecular mechanisms of breast cancer tumorigenesis enables the development of novel therapeutic strategies. SEC61G is a subunit of the endoplasmic reticulum translocon that plays critical roles in various tumors. We aimed to investigate the expression and function of SEC61G in breast cancer. By analyzing The Cancer Genome Atlas breast cancer cohort, we found that SEC61G was highly expressed in breast cancer and predicted poor prognosis of breast cancer patients. Overexpression of SEC61G and its prognostic role was also confirmed in the Nanjing Medical University (NMU) breast cancer cohort. Functionally, we demonstrated that knockdown of SEC61G suppressed breast cancer cell proliferation, migration, invasion, and promoted breast cancer cell apoptosis in vitro. Xenograft breast tumor model revealed that knockdown of SEC61G inhibited breast tumor development in vivo. Furthermore, we demonstrated that SEC61G positively regulated glycolysis in breast cancer cells. Mechanistically, we showed that transcription factor E2F1 directly bound to the promoter of SEC61G and regulated its expression in breast cancer cells. SEC61G overexpression antagonized the effect of E2F1 knockdown in regulating breast cancer cell proliferation, invasion, and apoptosis. Finally, we demonstrated that the E2F1/SEC61G axis regulated glycolysis and chemo-sensitivity of Herceptin in breast cancer cells. Taken together, these results of in vitro and in vivo studies demonstrate that SEC61G promotes breast cancer development and metastasis via modulating glycolysis and is transcriptionally regulated by E2F1, which might be utilized as a promising therapeutic target of breast cancer treatment.

The medical image management and analysis system proposed in this paper is a medical software developed by the Browser/Server (B/S) architecture after investigating the workflow of the relevant departments of the hospital, which realizes the entire process of patients from consultation to printing of reports. The computer-aided diagnosis function is added based on image management. Due to the difficulty in collecting medical image data, in the computer-aided diagnosis module, this paper only uses the common fungal keratitis collected from the hospital in the laboratory. Focused microscope images are used for experiments. First, the images were trained with three convolutional neural networks, AlexNet, ZFNet, and VGG16. These models which classify fungal keratitis were obtained and integrated was performed to obtain better classification results. Finally, the model was integrated with the system designed in this paper, which realized the automatic diagnosis of Confocal Microscopy (CM) images of fungal keratitis online and provided it to medical staff for reference. The system can improve the work efficiency of the image-related departments while reducing the workload of doctors in the department to manually read the films.