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Coal particles, a typical of organic matter with high carbon content, widely diffused in soil environment due to massive consumption of coal energy for centuries. Even in small amounts presented in soils, coal particles can produce obvious overestimation of soil organic carbon (SOC) and thus increase an uncertainty of soil C sequestration assessment. However, there is a lack of determination methods for distinguishing coal-derived C from SOC. This study takes the Jiaozuo mining area as the study area, which has a history of anthracite mining for more than 100 years and where coal-contaminated soils are widespread. The hyperspectral characteristics of the mine soils were analyzed by collecting coal particles and coal-free soils and then mixing known quantities of the two samples manually. Based on eight spectral mathematical transformation and two spectral feature screening methods (i.e., traditional correlation coefficiencies, and comprehensive competitive adaptive reweighted sampling (CARS)), six inversion models including spectral feature index models (i.e., deviation of arch (IDOA), difference index (ID), ratio index (IR)), and three machine learning models (i.e., partial least squares regression (PLSR), support vector machine (SVM) and random forest (RF)), were established to inversing coal-derived C content. The applicability of the established optimal inversion model was also examined. It was found that in the wavelength range from 350 nm to 2500 nm, the spectral curves of coal particles are obviously different from those of plant-derived organic matter and coal-free soils. Moreover, the spectral reflectance (R) of coal-contaminated soils decreases with increasing coal-derived C content. These findings provide a theoretical basis for the application of hyperspectral remote sensing technology to quantitatively inverse coal-derived C of mine soils. The CARS-extracted feature wavebands of coal-derived C distributed evenly in the wavelength range between 350 nm and 2500 nm, and the number of feature waveband extracted by the CARS was far higher than that by traditional correlation coefficiency methods. After mathematical transformation of R data, the estimated accuracies of coal-derived C content produced by the IDOA, ID and IR inversion models were significantly enhanced, among which, the DI model of 1/R spectral transformation exhibited the highest estimation accuracy. Compared with the traditional index models, the three machine learning models combined with CARS further enhanced estimation accuracy of coal-derived C content. Among the three machine learning models, the 1/R-CARS-RF inversion model produced the highest estimation accuracy, showing \begin{document}$R_{\rm{m}}^2 $\end{document}=0.998, RMSE=0.348, RPD=29.943 for its validation set. The applicability test showed that the 1/R-CARS-RF model exhibited a good applicability for different coal-contaminated soils in the Jiaozuo mining area as observed 1.88% for RMSE and 4.97 for RPD. Therefore, it can be expected that hyperspectral remote sensing technology has a promising application prospect for determining coal-derived C content in mine soils. In addition, this study can provide a methodology support for distinguishing coal-derived C from SOC in mine soils and accurately assessing soil carbon sequestration.

Cardiovascular diseases, such as heart attack and congestive heart failure, are the leading cause of death both in the United States and worldwide. The current medical practice for diagnosing cardiovascular diseases is not suitable for long-term, out-of-hospital use. A key to long-term monitoring is the ability to detect abnormal cardiac rhythms, i.e., arrhythmia, in real-time. Most existing studies only focus on the accuracy of arrhythmia classification, instead of runtime performance of the workflow. In this paper, we present our work on supporting real-time arrhythmic detection using convolutional neural networks, which take images of electrocardiogram (ECG) segments as input, and classify the arrhythmia conditions. To support real-time processing, we have carried out extensive experiments and evaluated the computational cost of each step of the classification workflow. Our results show that it is feasible to achieve real-time arrhythmic detection using convolutional neural networks. To further demonstrate the generalizability of this approach, we used the trained model with processed data collected by a customized wearable sensor from a lab setting, and the results shown that our approach is highly accurate and efficient. This research provides the potentials to enable in-home real-time heart monitoring based on 2D image data, which opens up opportunities for integrating both machine learning and traditional diagnostic approaches.

Hematopoiesis is a continuous and well-regulated process requiring both the capacity for self-renewal and the potential for differentiation of hematopoietic stem cells. Multiple studies indicate that sex hormones exert significant effects on not only hematopoietic stem and progenitor cells, but also the development of hematopoietic lineages, resulting in sexual dimorphisms in normal hematopoiesis. Hematologic malignancies comprise a wide variety of cancers affecting the blood, bone marrow, and lymphatic system, such as leukemia, lymphoma, myeloma, myelodysplastic syndrome, and myeloproliferative diseases. Overall, males are at greater risk and have worse prognosis for most of these malignancies compared with females. A better understanding of the differences between male and female could be of substantial value in research as well as clinical management.

Summary: Hematopoietic stem cells (HSCs) have the ability to self-renew and differentiate to all blood cell types. HSCs and their differentiated progeny show sex/gender differences. The fundamental mechanisms remain largely unexplored. We previously reported that latexin (Lxn) deletion increased HSC survival and repopulation capacity in female mice. Here, we find no differences in HSC function and hematopoiesis in Lxn knockout (Lxn−/−) male mice under physiologic and myelosuppressive conditions. We further find that Thbs1, a downstream target gene of Lxn in female HSCs, is repressed in male HSCs. Male-specific high expression of microRNA 98-3p (miR98-3p) contributes to Thbs1 suppression in male HSCs, thus abrogating the functional effect of Lxn in male HSCs and hematopoiesis. These findings uncover a regulatory mechanism involving a sex-chromosome-related microRNA and its differential control of Lxn-Thbs1 signaling in hematopoiesis and shed light on the process underlying sex dimorphism in both normal and malignant hematopoiesis.

Abstract Background Although advanced non-squamous non-small cell lung cancer (NSCLC) patients have significantly better survival outcomes after pemetrexed based treatment, a subset of patients still show intrinsic resistance and progress rapidly. Therefore we aimed to use a blood-based protein signature (VeriStrat, VS) to analyze whether VS could identify the subset of patients who had poor efficacy on pemetrexed therapy. Methods This study retrospectively analysed 72 advanced lung adenocarcinoma patients who received first-line pemetrexed/platinum or combined with bevacizumab treatment. Results Plasma samples from these patients were analysed using VS and classified into the Good (VS-G) or Poor (VS-P) group. The relationship between efficacy and VS status was further investigated. Of the 72 patients included in this study, 35 (48.6%) were treated with pemetrexed plus platinum and 37 (51.4%) were treated with pemetrexed/platinum combined with bevacizumab. Among all patients, 60 (83.3%) and 12 (16.7%) patients were classified as VS-G and VS-P, respectively. VS-G patients had significantly better median progression-free survival (PFS) (Unreached vs. 4.2 months; P

Abstract Background The five-year cumulative incidence rate in patients diagnosed with stage I small-cell lung cancer (SCLC) who were instructed to undergo surgery was from 40 to 60%.The death competition influence the accuracy of the classical survival analyses. The aim of the study is to investigate the mortality of stage I small-cell lung cancer (SCLC) patients in the presence of competing risks according to a proportional hazards model, and to establish a competing risk nomogram to predict probabilities of both cause-specific death and death resulting from other causes. Methods The study subjects were patients diagnosed with stage I SCLC according to ICD-O-3. First, the cumulative incidence functions (CIFs) of cause-specific death, as well as of death resulting from other causes, were calculated. Then, a proportional hazards model for the sub-distribution of competing risks and a monogram were constructed to evaluate the probability of mortality in stage I SCLC patients. Results 1811 patients were included in this study. The five-year probabilities of death due to specific causes and other causes were 61.5 and 13.6%, respectively. Tumor size, extent of tumor, surgery, and radiotherapy were identified as the predictors of death resulting from specific causes in stage I SCLC. The results showed that surgery could effectively reduce the cancer-specific death, and the one-year cumulative incidence dropped from 34.5 to 11.2%. Like surgery, chemotherapy and radiotherapy improved the one-year survival rate. Conclusions We constructed a predictive model for stage I SCLC using the data from the SEER database. The proportional sub-distribution models of competing risks revealed the predictors of death resulting from both specific causes and other causes. The competing risk nomogram that we built to predict the prognosis showed good reliability and could provide beneficial and individualized predictive information for stage I SCLC patients.

Edema toxin (ET), one of the main toxic factors of Bacillus anthracis (B. anthracis), is a kind of potent adenylate cyclase (AC). B. anthracis has adapted to resist macrophage microbicidal mechanisms in part by secreting ET. To date, there is limited information on the pathogenic mechanisms used by ET to manipulate macrophage function, especially at the transcriptome level. We used RNA sequencing to study transcriptional changes in RAW264.7 cells treated with ET. We aimed to identify molecular events associated with the establishment of infection and followed changes in cellular proteins. Our results indicate that ET inhibited TNF-α expression in the RAW264.7 mouse macrophage cell line by activating the cAMP/PKA pathway. ET challenge of macrophages induced a differential expression of genes that participate in multiple macrophage effector functions such as cytokine production, cell adhesion, and the inflammatory response. Furthermore, ET influenced the expression of components of the ERK1/2, as well as the NF-αB signaling pathways. We also showed that ET treatments inhibit the phosphorylation of the ERK1/2 protein. ET also attenuated NF-αB subunit p65 phosphorylation and transcriptional activity of NF-αB via the cAMP/PKA pathway in macrophages. Since the observed modulatory effects were characteristic only of the bacterial exotoxin ET, we propose this may be a mechanism used by B. anthracis to manipulate macrophages and establish systemic infection.

Messenger RNA (mRNA), which is composed of ribonucleotides that carry genetic information and direct protein synthesis, is transcribed from a strand of DNA as a template. On this basis, mRNA technology can take advantage of the body’s own translation system to express proteins with multiple functions for the treatment of various diseases. Due to the advancement of mRNA synthesis and purification, modification and sequence optimization technologies, and the emerging lipid nanomaterials and other delivery systems, mRNA therapeutic regimens are becoming clinically feasible and exhibit significant reliability in mRNA stability, translation efficiency, and controlled immunogenicity. Lipid nanoparticles (LNPs), currently the leading non-viral delivery vehicles, have made many exciting advances in clinical translation as part of the COVID-19 vaccines and therefore have the potential to accelerate the clinical translation of gene drugs. Additionally, due to their small size, biocompatibility, and biodegradability, LNPs can effectively deliver nucleic acids into cells, which is particularly important for the current mRNA regimens. Therefore, the cutting-edge LNP@mRNA regimens hold great promise for cancer vaccines, infectious disease prevention, protein replacement therapy, gene editing, and rare disease treatment. To shed more lights on LNP@mRNA, this paper mainly discusses the rational of choosing LNPs as the non-viral vectors to deliver mRNA, the general rules for mRNA optimization and LNP preparation, and the various parameters affecting the delivery efficiency of LNP@mRNA, and finally summarizes the current research status as well as the current challenges. The latest research progress of LNPs in the treatment of other diseases such as oncological, cardiovascular, and infectious diseases is also given. Finally, the future applications and perspectives for LNP@mRNA are generally introduced.

Background Taxane‐based chemotherapy is widely used in lung cancer. ABCB1 have a role in the prediction of treatment response and toxicity of chemotherapy in solid tumors. In this retrospective study, we investigated ABCB1 polymorphism on response and toxicity in taxane‐based chemotherapy in lung cancer patients. Methods A total of 122 lung cancer patients who received taxane‐based chemotherapy were included in this study. Fluorescence in situ hybridization (FISH) was used for ABCB1 polymorphism detection. Turbidimetric inhibition immunoassay was used for pharmacokinetic analysis. Statistical analysis was performed using SPSS 20.0. Results The frequency of the ABCB1 2677 site TT/TG/GG genotype was 32.8%, 43.4% and 23.8%, respectively and the frequency of the 3435 sites the TT/TC/CC genotype was 13.9%, 44.3% and 41.8%, respectively. The occurrence of neurotoxicity was higher in patients who had ABCB1 3435 site mutation (TT 88.2%, TC 22.2%, CC 21.6% P = 0.004). There was no significant difference between ABCB1 genotypes with regard to other chemotherapy‐induced toxicity. For non‐small cell lung cancer (NSCLC) patients, those harboring ABCB1 2677 and 3435 site wild‐type patients had longer median progression‐free survival (PFS) in the paclitaxel subgroup (3435 site: TT 3.87 vs. TC 9.50 vs. CC 14.13 months; P

Background Small‐cell lung cancer (SCLC) is one of the most aggressive types of lung cancer. The prognosis for SCLC patients depends on many factors. The intent of this study was to construct a nomogram model to predict mortality for extensive‐stage SCLC. Methods Original data was collected from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute in the United States. A nomogram prognostic model was constructed to predict death probability for extensive‐stage SCLC. Results A total of 16 554 extensive‐stage SCLC patients from 2004 to 2014 in the SEER database were included in this study. Gender, race, age, TNM staging (including tumor extent, nodal status, and metastasis), and treatment (surgery, chemotherapy, and radiotherapy) were identified as independent predictors for lung cancer‐specific death for extensive‐stage SCLC patients. A nomogram model was constructed based on multivariate models for lung cancer related death and other cause related death. Performance of the two models was validated by calibration and discrimination, with C‐index values of 0.714 and 0.638, respectively. Conclusion A prognostic nomogram model was established to predict death probability for extensive‐stage SCLC. This validated prognostic model may be beneficial for treatment strategy choice and survival prediction.

Background Primary tumors located in the right and left side have distinctive prognoses, but the details have not been fully identified in non‐small cell lung cancer (NSCLC). This study investigated the impact of primary tumor side on long‐term survival in NSCLC patients. Methods Data of 90 407 patients from the Surveillance, Epidemiology, and End Results (SEER) Program were analyzed. To avoid bias between groups, we used innovative propensity score matching (PSM) analysis. Results There was no significant distinction in overall survival (OS) between right (n = 53 496) and left (n = 36 911) side tumors (hazard ratio [HR] 0.993, 95% confidence interval [CI] 0.9756–1.011; P = 0.432). Left side was associated with superior five‐year cancer‐specific survival (CSS) compared to right side NSCLC (HR 0.977, 95% CI 0.9574–0.9969; P = 0.024). No significant difference was observed in OS (P = 0.689) or CSS (P = 0.288) after PSM analysis. In the 51 319 patients who underwent surgery, left side (n = 21 245) was associated with poor OS compared to right side (n = 30 074) NSCLC (HR 1.039, 95% CI 1.011–1.067; P = 0.006), while CSS was similar (HR 1.031, 95% CI 0.997–1.065; P = 0.069). In patients who underwent surgery, there was also no significant difference in OS (P = 0.986) or CSS (P = 0.979) after PSM analysis. Conclusion The prognosis between right and left side NSCLC in stage I–IIIA was similar regardless of whether patients underwent surgery. Primary tumor side cannot be considered a prognostic factor when choosing appropriate treatment.

Abstract Integration of the geological context, core analysis, and petrographic investigation, together with data from wireline logs, resulted in the recognition of petrofacies types and the representation of facies models characterizing the X–XII sand groups of the K2 qn 3 Formation in the Daqingzijing area of the Songliao Basin, China. The results show that the lithology of the reservoir’s X–XII sand groups includes shale calcium-bearing siltstone and sandstone, calcareous siltstone and silty sandstone. The petrofacies consist mainly of quartz, feldspar and rock fragments cemented by clay, and some samples include calcite. The studied interval was deposited onto a delta front. Four types of petrofacies were recognized: subaqueous distributary channel, mouth bar, distal bar and subaqueous interdistributary bay. According to background investigation, the study area’s X–XII sand groups have experienced a large-scale decline in lake level. There are many subaqueous distributary channels in layers 36–40, while other layers were mainly deposited in a subaqueous interdistributary bay.

Known as input in the Numerical Weather Prediction (NWP) models, Microwave Radiation Imager (MWRI) data have been widely distributed to the user community. With the development of remote sensing technology, improving the geolocation accuracy of MWRI data are required and the first step is to estimate the geolocation error accurately. However, the traditional method, such as the coastline inflection method (CIM), usually has the disadvantages of low accuracy and poor anti-noise ability. To overcome these limitations, this paper proposes a novel ℓ p iterative closest point coastline inflection method ( ℓ p -ICP CIM). It assumes that the field of views (FOVs) across the coastline can degenerate into a step function and employs an ℓ p ( 0 ≤ p < 1 ) sparse regularization optimization model to solve the coastline point. After estimating the coastline points, the ICP algorithm is employed to estimate the corresponding relationship between the estimated coastline points and the real coastline. Finally, the geolocation error can be defined as the distance between the estimated coastline point and the corresponding point on the true coastline. Experimental results on simulated and real data sets show the effectiveness of our method over CIM. The accuracy of the geolocation error estimated by ℓ p -ICP CIM is up to 0.1 pixel, in more than 90 % of cases. We also show that the distribution of brightness temperature near the coastline is more consistent with the real coastline and the average geolocation error is reduced by 63 % after geolocation error correction.

Leptospirosis is a re-emerging tropical infectious disease caused by pathogenic Leptospira spp. The different host innate immune responses are partially related to the different severities of leptospirosis. In this study, we employed transcriptomics and cytokine arrays to comparatively calculate the responses of murine peritoneal macrophages (MPMs) and human peripheral blood monocytes (HBMs) to leptospiral infection. We uncovered a series of different expression profiles of these two immune cells. The percentages of regulated genes in several biological processes of MPMs, such as antigen processing and presentation, membrane potential regulation, and the innate immune response, etc., were much greater than those of HBMs (>2-fold). In MPMs and HBMs, the caspase-8 and Fas-associated protein with death domain (FADD)-like apoptosis regulator genes were significantly up-regulated, which supported previous results that the caspase-8 and caspase-3 pathways play an important role in macrophage apoptosis during leptospiral infection. In addition, the key component of the complement pathway, C3, was only up-regulated in MPMs. Furthermore, several cytokines, e.g. interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-alpha), were differentially expressed at both mRNA and protein levels in MPMs and HBMs. Some of the differential expressions were proved to be pathogenic Leptospira-specific regulations at mRNA level or protein level. Though it is still unclear why some animals are resistant and others are susceptible to leptospiral infection, this comparative study based on transcriptomics and cytokine arrays partially uncovered the differences of murine resistance and human susceptibility to leptospirosis. Taken together, these findings will facilitate further molecular studies on the innate immune response to leptospiral infection.

Edema toxin (ET), which is composed of a potent adenylate cyclase (AC), edema factor (EF), and protective antigen (PA), is one of the major toxicity factors of Bacillus anthracis. In this study, we introduced mutations in full-length EF to generate alanine EF(H351A) and arginine EF(H351R) variants. In vitro activity analysis displayed that the adenylyl cyclase activity of both the mutants was significantly diminished compared with the wild-type EF. When the native and mutant toxins were administered subcutaneously in a mouse footpad edema model, severe acute swelling was evoked by wild-type ET, while the symptoms induced by mutant toxins were very minor. Systemic administration of these EF variants caused non-lethal hepatotoxicity. In addition, EF(H351R) exhibited slightly higher activity in causing more severe edema than EF(H351A). Our findings demonstrate that the toxicity of ET is not abolished by substitution of EF residue His351 by alanine or arginine. These results also indicate the potential of the mouse footpad edema model as a sensitive method for evaluating both ET toxicity and the efficacy of candidate therapeutic agents.