The aim of this study was to identify the changes of hematologic and immunological parameters in COVID-19 patients. We collected and analyzed the data of 117 patients who were laboratory confirmed as ...SARS-CoV-2 infection. The cases were divided into regular group, severe group and critically ill group according to the sixth edition scheme for COVID-19 diagnosis and treatment of China. The laboratory tests included blood routine, cellular and humoral immunity indices, biochemical detections and inflammatory biomarker. Compared with regular patients, severe and critically ill patients had significantly lower lymphocyte count (
p
< 0.01), decreased red blood cell and hemoglobin (
p
< 0.01), low levels of immunoglobulin G (
p
< 0.05) and significantly higher in D-dimer (
p
< 0.0001), fibrinogen (
p
< 0.01), white blood cell count (
p
< 0.01), neutrophil count (
p
< 0.0001), interleukin-6 (
p
< 0.05), C-reactive protein (
p
< 0.01), procalcitonin (
p
< 0.01), erythrocyte sedimentation rate (
p
< 0.05), ferritin (
p
< 0.01) and lactate dehydrogenase (
p
< 0.0001). The specific immunoglobulin G antibodies to the SARS-CoV-2 in severe and critically ill patients were significantly lower than that in regular patients (
p
< 0.05). Our findings suggest that the lymphocyte counts, red blood cell counts and the immunoglobulin G antibodies of COVID-19 patients were impaired to varying degrees and the blood was in a state of hypercoagulation, which were more obvious in critically ill patients.
As Internet of Things (IoT) networks expand globally with an annual increase of active devices, providing better safeguards to threats is becoming more prominent. An intrusion detection system (IDS) ...is the most viable solution that mitigates the threats of cyberattacks. Given the many constraints of the ever-changing network environment of IoT devices, an effective yet lightweight IDS is required to detect cyber anomalies and categorize various cyberattacks. Additionally, most publicly available datasets used for research do not reflect the recent network behaviors, nor are they made from IoT networks. To address these issues, in this paper, we have the following contributions: (1) we create a dataset from IoT networks, namely, the Center for Cyber Defense (CCD) IoT Network Intrusion Dataset V1 (CCD-INID-V1); (2) we propose a hybrid lightweight form of IDS—an embedded model (EM) for feature selection and a convolutional neural network (CNN) for attack detection and classification. The proposed method has two models: (a) RCNN: Random Forest (RF) is combined with CNN and (b) XCNN: eXtreme Gradient Boosting (XGBoost) is combined with CNN. RF and XGBoost are the embedded models to reduce less impactful features. (3) We attempt anomaly (binary) classifications and attack-based (multiclass) classifications on CCD-INID-V1 and two other IoT datasets, the detection_of_IoT_botnet_attacks_N_BaIoT dataset (Balot) and the CIRA-CIC-DoHBrw-2020 dataset (DoH20), to explore the effectiveness of these learning-based security models. Using RCNN, we achieved an Area under the Receiver Characteristic Operator (ROC) Curve (AUC) score of 0.956 with a runtime of 32.28 s on CCD-INID-V1, 0.999 with a runtime of 71.46 s on Balot, and 0.986 with a runtime of 35.45 s on DoH20. Using XCNN, we achieved an AUC score of 0.998 with a runtime of 51.38 s for CCD-INID-V1, 0.999 with a runtime of 72.12 s for Balot, and 0.999 with a runtime of 72.91 s for DoH20. Compared to KNN, XCNN required 86.98% less computational time, and RCNN required 91.74% less computational time to achieve equal or better accurate anomaly detections. We find XCNN and RCNN are consistently efficient and handle scalability well; in particular, 1000 times faster than KNN when dealing with a relatively larger dataset-Balot. Finally, we highlight RCNN and XCNN’s ability to accurately detect anomalies with a significant reduction in computational time. This advantage grants flexibility for the IDS placement strategy. Our IDS can be placed at a central server as well as resource-constrained edge devices. Our lightweight IDS requires low train time and hence decreases reaction time to zero-day attacks.
Psoriasis is a T cells mediated chronic skin inflammation in which helper T (Th) cells play in critical roles in its pathogenesis. Taxifolin (TXL) has been discovered to exert various pharmacological ...activities. In this study, we wished to observe whether TXL had potential activities on psoriasis, and how it works. We found that TXL can inhibit LPS-induced abnormal proliferation in Hacat cell line, ant also significantly alleviate the IMQ-induced psoriasis in BALB/c mice, comparing with the control group. Although TXL has no significant effects on the ratio of total T cells in skin draining lymph nodes (SDLN), it decreases the ratio of pro-inflammatory Th1 and Th17 cells, both in skin lesions and SDLN. Our results also disclosed that TXL may regulate Th cells differentiation by inhibiting the transcript factors, including T-bet, GATA-3 and RORγt. Further data show that TXL can inhibit Notch1 and Jak2/Stat3 signal pathways. In summary, TXL may be able to treat psoriasis by regulating Th cells differentiation via inhibiting Notch1 and Jak2/Stat3 pathways.
Abstract
A complete understanding of the structural and functional potential of RNA requires understanding of chemical modifications and non-canonical bases; this in turn requires advances in current ...sequencing methods to be able to sequence not only canonical ribonucleotides, but at the same time directly sequence these non-standard moieties. Here, we present the first direct and modification type-independent RNA sequencing method via introduction of a 2-dimensional hydrophobic end-labeling strategy into traditional mass spectrometry-based sequencing (2D HELS MS Seq) to allow de novo sequencing of RNA mixtures and enhance sample usage efficiency. Our method can directly read out the complete sequence, while identifying, locating, and quantifying base modifications accurately in both single and mixed RNA samples containing multiple different modifications at single-base resolution. Our method can also quantify stoichiometry/percentage of modified RNA versus its canonical counterpart RNA, simulating a real biological sample where modifications exist but may not be 100% at a particular site in the RNA. This method is a critical step towards fully sequencing real complex cellular RNA samples of any type and containing any modification type and can also be used in the quality control of modified therapeutic RNAs.
An intrusion detection system (IDS) identifies whether the network traffic behavior is normal or abnormal or identifies the attack types. Recently, deep learning has emerged as a successful approach ...in IDSs, having a high accuracy rate with its distinctive learning mechanism. In this research, we developed a new method for intrusion detection to classify the NSL-KDD dataset by combining a genetic algorithm (GA) for optimal feature selection and long short-term memory (LSTM) with a recurrent neural network (RNN). We found that using LSTM-RNN classifiers with the optimal feature set improves intrusion detection. The performance of the IDS was analyzed by calculating the accuracy, recall, precision, f-score, and confusion matrix. The NSL-KDD dataset was used to analyze the performances of the classifiers. An LSTM-RNN was used to classify the NSL-KDD datasets into binary (normal and abnormal) and multi-class (Normal, DoS, Probing, U2R, and R2L) sets. The results indicate that applying the GA increases the classification accuracy of LSTM-RNN in both binary and multi-class classification. The results of the LSTM-RNN classifier were also compared with the results using a support vector machine (SVM) and random forest (RF). For multi-class classification, the classification accuracy of LSTM-RNN with the GA model is much higher than SVM and RF. For binary classification, the classification accuracy of LSTM-RNN is similar to that of RF and higher than that of SVM.
Abstract BACKGROUND: The prognostic value of tumor-infiltrating lymphocytes (TILs) in head and neck squamous cell carcinoma (HNSCC) remains controversial. Additionally, there is no standardized ...approach or cutoff value for evaluating TIL levels. The aim of this study was to establish a feasible method and criterion to assess TIL levels for future clinical practice and research use and to explore the relationship between TIL levels and prognosis. PATIENTS AND METHODS: This retrospective cohort study reviewed the records and pathological sections of 202 patients with HNSCC who were surgically treated at Beijing Stomatological Hospital, Capital Medical University, from January 1998 to January 2011. The predictor variable was the TIL level. The main outcome assessment parameters were disease-free survival (DFS) and disease-specific survival (DSS). RESULT: The T stage ( P = .008), smoking history ( P = .042), alcohol history ( P = .048), need for radiotherapy ( P = .012) and microscopic extracapsular spread (ECS) ( P = .012) were associated with the TIL level. A cutoff value equal to 70% could be taken as a threshold for TIL assessment, with a TIL level higher than 70% associated with a better prognosis (DFS rate: 51.9%, P = .018; DSS rate: 59.3%, P = .049). The Cox regression model showed that the TIL level was an independent prognostic factor for DFS (hazard ratio (HR): 0.786, 95% CI: 0.618-0.999, P = .049). CONCLUSION: The TIL level is closely related to the prognosis of patients with HNSCC. A threshold value of 70% is appropriate for TIL assessment, as patients with a TIL level higher than 70% show a better prognosis. Thus, the TIL level might serve as an independent predictor for HNSCC recurrence.
Background Autologous stem cell transplantation (ASCT) is a potentially curative strategy for relapse or refractory(r/r) aggressive lymphoma. However, a proportion of lymphoma patients who are at ...high risk of mobilization failure fail to mobilize stem cells and cannot proceed to ASCT. The aim of this study is to explore the efficacy and safety of Etoposide combined with Cytarabine (EA) plus G-CSF mobilization in poor mobilizers (PMs) with r/r aggressive lymphoma. Methods This retrospective study analyzed the outcomes of chemo-mobilization based on EA (Etoposide 0.1 g/m2, qd d1~3; AraC 0.5 g/m2, q12h d1~3) in 98 patients with r/r aggressive lymphoma. Of these, 39 patients met the criteria for predicted PMs as proposed by the Gruppo Italiano Trapianto di Midollo Osseo working group. Results Of the 39 PMs, 38(97.4%) patents harvested adequate mobilization (≥2×10 6 CD34+ cells/kg), while 31(79.5%) patients achieved optimal mobilization (≥5×10 6 CD34+ cells/kg). Overall, the mean number of CD34+ cells/kg collected was 17.99(range: 1.08~83.07) ×10 6 with an average of 1.4 apheresis sessions, and the number was 15.86(range: 0.37~83.07) ×10 6 for the first apheresis, respectively. A single apheresis procedure was sufficient to reach the target yield of adequate mobilization in 35(89.7%) PMs, while 76.9% of PMs achieved optimal collection within two apheresis sessions. We observed acceptable hematological toxicity and antibiotic usage exposure in 26 patients with a mean duration of 3.6 days. No grade 4 infection or mobilization-related mortality was recorded. Most patients underwent ASCT and achieved successful hematopoietic recovery with prompt engraftment duration, except for one NK/T-cell lymphoma patient who succumbed to severe septicemia after receiving conditioning chemotherapy. Conclusion Our findings indicate that EA plus G-CSF is an effective and tolerable CD34+ stem cell mobilization strategy for patients with r/r lymphoma, including those predicted to be PMs. This regimen could be an option for patients with r/r lymphoma, particularly those undergoing mobilization for salvage ASCT therapy.
At present, it is generally believed that leukemia stem cells are the source of AML, so the killing of leukemia stem cells has become important. Previous studies have suggested that HHT combined with ...ATO can synergistically kill U937 cells, and HHT has also demonstrated the ability to kill leukemia stem cells. We evaluated whether HHT combined with ATO can systematically kill leukemia stem cells (LSCs) and explored the synergistic effect and molecular mechanism.
CCK-8 was used to detect cell viability. The changes of cell cycle (PI staining), apoptosis (Annexin V/PI) and surface markers (CD34, CD38, CD96, CD45) were detected by flow cytometry. The cells of CD34+ primary leukemia and CD38- KG-1, and TF-1 were separated by flow cytometry. High-throughput mRNA sequencing was used to analysis mRNA level changes after the application of the two drugs. Western blot was used to verify the changes of pathway protein expression. NRG mice were used as the receptor of xenograft model. Histological H&E staining assess the invaded ability of leukemia cells, and laser scanning confocal microscopy evaluated the molecule markers change.
HHT and ATO synergistically killed KG-1 (CD34
/CD96
/CD38
/
) and Kasumi-1 (CD34
/CD38
) cells. Their combination had a stronger effect of inducing apoptosis and blocking the cell cycle than HHT or ATO administrator alone, meanwhile significantly reducing the numbers of LSCs. Further, CD34
CD38
cells in KG-1, KG-1a, TF-1, and primary leukemia cells were more sensitive to HHT and ATO. High-throughput mRNA sequencing suggested that HHT alone could significantly upregulate molecules related to the Notch, P53, and NF-κB signaling pathways. When combined with ATO, HHT further upregulated P53, whereas HHT-induced NF-κB pathway activation was significantly suppressed. Western blot analysis verified the change of protein expression in the above pathways and further demonstrated that GSI, could eliminate these effects. In vivo, HHT combined with ATO significantly reduced the LSC burden, and weakened the expression of LSC markers.
This is the first evidence that HHT combined with arsenic can synergistically kill LSCs in vitro and in vivo, along with identification of the underlying mechanism, highlighting a potentially effective treatment strategy.
Al/TiO₂ composite film was successfully deposited on polyester fabrics by using magnetron sputtering techniques. X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) were used to ...examine the deposited films on the fabrics, and the structural colors and anti-ultraviolet property of fabrics were also analyzed. The results indicated that polyester fabrics coated with Al/TiO₂ composite films achieved structural colors. The reactive sputtering times of TiO₂ films in Al/TiO₂ composite films were 10 min, 12 min, 18 min, 20 min, 26 min, 27 min, 30 min and 45 min, respectively, the colors of corresponding fabrics were bluish violet, blue, cyan, green, yellow, yellowish red, orange and blue-green, which was consistent with the principle of the thin film interference. The structure of the TiO₂ film in Al/TiO₂ composite films was non-crystalline, though the fabrics were heated and maintained at the temperature of 200 °C. The anti-ultraviolet property of the fabrics deposited with Al/TiO₂ composite films were excellent because of the effect of Al/TiO₂ composite films.
Graphitic
carbon nitride (g-CN) has emerged as a promising metal-free
photocatalyst, while the catalytic mechanism for the photoinduced
redox processes is still under investigation. Interestingly, ...this
heptazine-based polymer optically behaves as a “quasi-monomer”.
In this work, we explore upstream from melem (the heptazine monomer)
to the triazine-based melamine and melam and present several lines
of theoretical/experimental evidence where the catalytic activity
of g-CN originates from the electronic structure evolution of the
C–N heterocyclic cores. Periodic density functional theory
calculations reveal the strikingly different electronic structures
of melem from its triazine-based counterparts. Fourier transform infrared
spectroscopy and X-ray photoelectron spectroscopy also provide consistent
results in the structural and chemical bonding variations of these
three relevant compounds. Both melam and melem were found to show
stable photocatalytic activities, while the photocatalytic activity
of melem is about 5.4 times higher than that of melam during the degradation
of dyes under UV–visible light irradiation. In contrast to
melamine and melam, the frontier electronic orbitals of the heptazine
unit in melem are uniformly distributed and well complementary to
each other, which further determine the terminal amines as primary
reduction sites. These appealing electronic features in both the heterocyclic
skeleton and the terminated functional groups can be inherited by
the polymeric but quasi-monomeric g-CN, leading to its pronounced
photocatalytic activity.
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