Mast cell degranulation-triggered by SARS-CoV-2 induces tracheal-bronchial epithelial inflammation and injury.

SARS-CoV-2 infection-induced hyper-inflammation is a key pathogenic factor of COVID-19. Our research, along with others', has demonstrated that mast cells (MCs) play a vital role in the initiation of hyper-inflammation caused by SARS-CoV-2. In previous study, we observed that SARS-CoV-2 infection induced the accumulation of MCs in the peri-bronchus and bronchioalveolar-duct junction in humanized mice. Additionally, we found that MC degranulation triggered by the spike protein resulted in inflammation in alveolar epithelial cells and capillary endothelial cells, leading to subsequent lung injury. The trachea and bronchus are the routes for SARS-CoV-2 transmission after virus inhalation, and inflammation in these regions could promote viral spread. MCs are widely distributed throughout the respiratory tract. Thus, in this study, we investigated the role of MCs and their degranulation in the development of inflammation in tracheal-bronchial epithelium. Histological analyses showed the accumulation and degranulation of MCs in the peri-trachea of humanized mice infected with SARS-CoV-2. MC degranulation caused lesions in trachea, and the formation of papillary hyperplasia was observed. Through transcriptome analysis in bronchial epithelial cells, we found that MC degranulation significantly altered multiple cellular signaling, particularly, leading to upregulated immune responses and inflammation. The administration of ebastine or loratadine effectively suppressed the induction of inflammatory factors in bronchial epithelial cells and alleviated tracheal injury in mice. Taken together, our findings confirm the essential role of MC degranulation in SARS-CoV-2-induced hyper-inflammation and the subsequent tissue lesions. Furthermore, our results support the use of ebastine or loratadine to inhibit SARS-CoV-2-triggered degranulation, thereby preventing tissue damage caused by hyper-inflammation.

Attractive effects of previous form information on heading estimation from optic flow occur at perceptual stage.

When moving in the environment, optic flow and form (e.g., motion streaks) information generally appear simultaneously. Previous studies have shown that observers can estimate their heading by integrating the simultaneously presented form and optic flow information. Recent work also found that the previously seen optic flow affected the current heading estimation. The current study conducted two experiments to explore whether and how the heading estimation from optic flow was affected by the previously seen form information. We found that the current heading estimates from optic flow were biased toward the location of the focus of expansion of the previously seen form stimulus, showing an attractive effect of the previous form. Additionally, the results revealed that the attractive effect of the previous form occurred at the perceptual stage rather than postperceptual stages (e.g., working memory). Our findings suggest that our visual system can integrate dynamic optic flow and static form information across the temporal domain to estimate our heading direction.

Identification of a differentiation-related prognostic nomogram based on single-cell RNA sequencing in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is a kidney cancer that is originated from the lined proximal convoluted tubule, and its major histological subtype is clear cell RCC (ccRCC). This study aimed to retrospectively analyze single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, to explore the correlation among the evolution of tumor microenvironment (TME), clinical outcomes, and potential immunotherapeutic responses in combination with bulk RNA-seq data from The Cancer Genome Atlas (TCGA) database, and to construct a differentiation-related genes (DRG)-based prognostic risk signature (PRS) and a nomogram to predict the prognosis of ccRCC patients. First, scRNA-seq data of ccRCC samples were systematically analyzed, and three subsets with distinct differentiation trajectories were identified. Then, ccRCC samples from TCGA database were divided into four DRG-based molecular subtypes, and it was revealed that the molecular subtypes were significantly correlated with prognosis, clinicopathological features, TME, and the expression levels of immune checkpoint genes (ICGs). A DRG-based PRS was constructed, and it was an independent prognostic factor, which could well predict the prognosis of ccRCC patients. Finally, we constructed a prognostic nomogram based on the PRS and clinicopathological characteristics, which exhibited a high accuracy and a robust predictive performance. This study highlighted the significance of trajectory differentiation of ccRCC cells and TME evolution in predicting clinical outcomes and potential immunotherapeutic responses of ccRCC patients, and the nomogram provided an intuitive and accurate method for predicting the prognosis of such patients.

A new image encryption algorithm based on the OF-LSTMS and chaotic sequences.

In this paper, a novel image encryption algorithm based on the Once Forward Long Short Term Memory Structure (OF-LSTMS) and the Two-Dimensional Coupled Map Lattice (2DCML) fractional-order chaotic system is proposed. The original image is divided into several image blocks, each of which is input into the OF-LSTMS as a pixel sub-sequence. According to the chaotic sequences generated by the 2DCML fractional-order chaotic system, the parameters of the input gate, output gate and memory unit of the OF-LSTMS are initialized, and the pixel positions are changed at the same time of changing the pixel values, achieving the synchronization of permutation and diffusion operations, which greatly improves the efficiency of image encryption and reduces the time consumption. In addition the 2DCML fractional-order chaotic system has better chaotic ergodicity and the values of chaotic sequences are larger than the traditional chaotic system. Therefore, it is very suitable to image encryption. Many simulation results show that the proposed scheme has higher security and efficiency comparing with previous schemes.

IGLL5 is correlated with tumor-infiltrating immune cells in clear cell renal cell carcinoma.

Renal cell carcinomas (RCCs) account for about 90% of renal tumors, and their major histological subtype is ccRCC (clear cell RCC). Increasing evidence has indicated that the tumor microenvironment plays a significant role in the occurrence and development of ccRCC. In this study, we used ESTIMATE and CIBERSORT computational methods to calculate the proportion of immune and stromal components and the rate of TICs (tumor-infiltrating immune cells) in 539 ccRCC samples from The Cancer Genome Atlas database. By examining the intersection of the differentially expressed genes obtained by the protein-protein interaction network and Cox regression analysis, we identified only one overlapping gene: IGLL5 (immunoglobulin lambda-like polypeptide 5). We report that IGLL5 expression is correlated with TICs. Furthermore, our immunoinfiltration analyses revealed that three types of TIC are positively correlated with IGLL5 expression. IGLL5 may have potential as a prognostic biomarker of ccRCC.

Morphological and anatomical characteristics of exserted stigma sterility and the location and function of SlLst (Solanum lycopersicum Long styles) gene in tomato.

KEY MESSAGE: Anatomical changes in and hormone roles of the exserted stigma were investigated, and localization and functional analysis of SlLst for the exserted stigma were performed using SLAF-BSA-seq, parental resequencing and overexpression of SlLst in tomato. Tomato accession T431 produces stigmas under relatively high temperatures (> 27 °C, the average temperature in Harbin, China, in June-August), so pollen can rarely reach the stigma properly. This allows the percentage of male sterility exceed 95%, making the use of this accession practical for hybrid seed production. To investigate the mechanism underlying the exserted stigma male sterility, the morphological changes of, anatomical changes of, and comparative endogenous hormone (IAA, ABA, GA3, ZT, SA) changes in flowers during flower development of tomato accessions DL5 and T431 were measured. The location and function of genes controlling exserted stigma sterility were analyzed using super SLAF-BSA-seq, parental resequencing, comparative genomics and the overexpression of SlLst in tomato. The results showed that an increase in cell number mainly caused stigma exsertion. IAA played a major role, while ABA had an opposite effect on stigma exertion. Moreover, 26 candidate genes related to the exserted stigma were found, located on chromosome 12. The Solyc12g027610.1 (SlLst) gene was identified as the key candidate gene by functional analysis. A subcellular localization assay revealed that SlLst is targeted to the nucleus and cell membrane. Phenotypic analysis of SlLst-overexpressing tomato showed that SlLst plays a crucial role during stigma exsertion.

[Sorption Behaviors of Copper Ions and Tetracycline on Microplastics in Aqueous Solution].

The interaction between microplastics, heavy metals, and antibiotics can lead to combined pollution, which could result in greater environmental damage. The pathway and mechanism of the interaction between microplastics, heavy metals, and antibiotics are the preconditions for evaluating the associated environmental risk; however, these are not well understood. As probe sorbates, the sorption behaviors of copper ions (Cu2+) and tetracycline (TC) on two microplastics [high density polyethylene (HPDE) and general-purpose polystyrene (GPPS)] in aqueous solution were investigated and the welding theory with relevant experimental results were discussed. The adsorption capacity of HDPE was greater than that of GPPS in a single Cu solution, whereas the reverse situation occurred in a single TC solution. Moreover, the adsorption capacity of the microplastics in a Cu2+-TC binary solution was larger than that in the single solutions. The pseudo-second-order kinetic models to describe the adsorption process were reasonable and the entire process could be divided into two phases:surface adsorption and internal diffusion. The Langmuir model provided a better fit of the data than did the Freundlich model. In the single solutions, the saturated adsorption amounts of Cu2+ and TC were 0.178 µmol·g-1 and 0.257 µmol·g-1, respectively, for GPPS, and 0.334 µmol·g-1 and 0.194 µmol·g-1, respectively, for HDPE. In the binary solution, the corresponding numerical values were 0.529 µmol·g-1 and 0.411 µmol·g-1, respectively, for GPPS and 0.471 µmol·g-1 and 0.341 µmol·g-1, respectively, for HDPE. The variations in the surface morphological characteristics and chemical functional groups were the main reasons for the difference in the adsorption behavior of microplastics. The variation of the pH of the adsorption system could change the existing forms and surface electrical properties of microplastics and adsorbed objects, and subsequently affected the equilibrium adsorption capacity. When the ambient temperature was in the range of 15 to 35℃, increasing the temperature was unfavorable for the adsorption process. Cu2+ and TC could produce a synergistic effect under the conditions of coexistence. The formation of complexes and bridging make Cu2+ and TC more easily adsorbed by microplastics.

BMP8A promotes survival and drug resistance via Nrf2/TRIM24 signaling pathway in clear cell renal cell carcinoma.

There is increasing evidence that bone morphogenetic proteins (BMP) are involved in the proliferation and drug tolerance of kidney cancer. However, the molecular mechanism of BMP8A in renal cell proliferation and drug tolerance is not clear. Here we showed that BMP8A was highly expressed in renal cell carcinoma, which suggests a poor prognosis of ccRCC. Promotion of cell proliferation and inhibition of apoptosis were detected by CCK-8 assay, Trypan Blue staining, flow cytometry and bioluminescence. BMP8A promoted resistance of As2 O3 by regulating Nrf2 and Wnt pathways in vitro and in vivo. Mechanistically, BMP8A enhanced phosphorylation of Nrf2, which, in turn, inhibited Keap1-mediated Nrf2 ubiquitination and, ultimately, promoted nuclear translocation and transcriptional activity of Nrf2. Nrf2 regulates the transcription of TRIM24 detected by ChIP-qPCR. BMP8A was highly expressed in ccRCC, which suggests a poor prognosis. BMP8A was expected to be an independent prognostic molecule for ccRCC. On the one hand, activated Nrf2 regulated reactive oxygen balance, and on the other hand, by regulating the transcription level of TRIM24, it was involved in the regulation of the Wnt pathway to promote the proliferation, invasion and metastasis of ccRCC and the resistance of As2 O3 . Taken together, our findings describe a regulatory axis where BMP8A promotes Nrf2 phosphorylation and activates TRIM24 to promote survival and drug resistance in ccRCC.

Unusual scaling laws for plasmonic nanolasers beyond the diffraction limit.

Plasmonic nanolasers are a new class of amplifiers that generate coherent light well below the diffraction barrier bringing fundamentally new capabilities to biochemical sensing, super-resolution imaging, and on-chip optical communication. However, a debate about whether metals can enhance the performance of lasers has persisted due to the unavoidable fact that metallic absorption intrinsically scales with field confinement. Here, we report plasmonic nanolasers with extremely low thresholds on the order of 10 kW cm-2 at room temperature, which are comparable to those found in modern laser diodes. More importantly, we find unusual scaling laws allowing plasmonic lasers to be more compact and faster with lower threshold and power consumption than photonic lasers when the cavity size approaches or surpasses the diffraction limit. This clarifies the long-standing debate over the viability of metal confinement and feedback strategies in laser technology and identifies situations where plasmonic lasers can have clear practical advantage.

Imaging the dark emission of spasers.

Spasers are a new class of laser devices with cavity sizes free from optical diffraction limit. They are an emergent tool for various applications, including biochemical sensing, superresolution imaging, and on-chip optical communication. According to its original definition, a spaser is a coherent surface plasmon amplifier that does not necessarily generate a radiative photon output. However, to date, spasers have only been studied with scattered photons, and their intrinsic surface plasmon emission is a "dark" emission that is yet to be revealed because of its evanescent nature. We directly image the surface plasmon emission of spasers in spatial, momentum, and frequency spaces simultaneously. We demonstrate a nanowire spaser with a coupling efficiency to plasmonic modes of 74%. This coupling efficiency can approach 100% in theory when the diameter of the nanowire becomes smaller than 50 nm. Our results provide clear evidence of the surface plasmon amplifier nature of spasers and will pave the way for their various applications.

Color image encryption scheme using CML and DNA sequence operations.

In this paper, an encryption algorithm for color images using chaotic system and DNA (Deoxyribonucleic acid) sequence operations is proposed. Three components for the color plain image is employed to construct a matrix, then perform confusion operation on the pixels matrix generated by the spatiotemporal chaos system, i.e., CML (coupled map lattice). DNA encoding rules, and decoding rules are introduced in the permutation phase. The extended Hamming distance is proposed to generate new initial values for CML iteration combining color plain image. Permute the rows and columns of the DNA matrix and then get the color cipher image from this matrix. Theoretical analysis and experimental results prove the cryptosystem secure and practical, and it is suitable for encrypting color images of any size.

Stability and synchronization for discrete-time complex-valued neural networks with time-varying delays.

In this paper, the synchronization problem for a class of discrete-time complex-valued neural networks with time-varying delays is investigated. Compared with the previous work, the time delay and parameters are assumed to be time-varying. By separating the real part and imaginary part, the discrete-time model of complex-valued neural networks is derived. Moreover, by using the complex-valued Lyapunov-Krasovskii functional method and linear matrix inequality as tools, sufficient conditions of the synchronization stability are obtained. In numerical simulation, examples are presented to show the effectiveness of our method.

[Prognostic analysis of patients with liver metastases from colorectal cancer treated with different modes of therapy].

OBJECTIVE: To investigate the potential prognostic factors for patients with liver metastases from colorectal cancer treated with different modes of therapy. METHODS: The clinicopathological data of 300 patients with liver metastases from colorectal cancers were retrospectively reviewed and analyzed. RESULTS: The median survival of patients with recurrence (MSR) treated with complete and palliative resection of liver metastases and unresectable patients was 48, 19 and 18 months, respectively (P = 0.000). In patients with unresectable liver metastases, systemic chemotherapy plus regional therapy demonstrated a median survival time of 23 months, significantly longer than the 6 months in untreated patients (P = 0.000). Patients who showed response to the first-line therapy demonstrated an improved survival versus the patients who had no response, with a median survival time of 24 vs. 16 months (P = 0.000). Univariate analysis revealed that resection modes of primary diseases and liver metastases, treatment modality for liver metastases, and response to first-line therapy were prognostic factors. Multivariate analysis showed that resection modes of liver metastases, multimodality treatment after liver metastases, and the response to first-line therapy were all independent prognostic factors for patients with liver metastases from colorectal cancer. CONCLUSION: Resection of liver metastases, multimodality treatment after liver metastases, and response to first-line chemotherapy are all independent prognostic factors for patients with liver metastasis from colorectal cancer.

[Analysis of prognostic factors in 300 colorectal cancer patients with liver metastases].

OBJECTIVE: To analyse the clinical characteristics and potential prognostic factors of colorectal cancer patients with liver metastases. METHODS: The clinical and pathological data of 300 colorectal cancer patients with liver metastases were retrospectively reviewed and analyzed. RESULTS: The median survival time of these patients was 19.0 months. The 1-, 2- and 5-year survival rates after liver metastases were 79.0%, 29.0% and 3.0%, respectively. Univariate analysis revealed that performance status (KPS), histological grading, primary tumor, N status, lymphatic and vascular invasion, stage at diagnosis, the number, size and distribution of liver metastases and other accompanied metastases were prognostic factors. Multivariate analysis showed that KPS, lymphatic and vascular invasion, the number and size of liver metastases were independent prognostic factors of colorectal cancer with liver metastases. CONCLUSION: Performance status, lymphatic and vascular invasion, the number and size of liver metastases are independent prognostic factors of colorectal cancer with liver metastases.

Dynamic analysis of the fractional-order Liu system and its synchronization.

Based on the stability theory of fractional-order systems, the dynamic behaviors of fractional-order Liu system are studied theoretically. Coupling synchronization of two identical fractional-order chaotic systems is also studied and a simple criterion is presented. Numerical simulations show the effectiveness of our methods.

Robust anti-synchronization of a class of delayed chaotic neural networks.

This paper deals with the anti-synchronization problem of a class of delayed neural networks. Based on the Lyapunov stability theory and the Halanay inequality lemma, a kind of controller is designed. It is proved that this kind of controller can achieve anti-synchronization of neural networks with delays. Numerical simulations demonstrate the effectiveness and robustness of the proposed anti-synchronization scheme.

Tracking control and synchronization of four-dimensional hyperchaotic Rossler system.

In this paper we study the problem of the four-dimensional hyperchaotic Rossler system tracking control. A controller based on the reference signal is designed. It is theoretically proved that the controller can make the error converge to zero exponentially. Numerical results have verified the validity of the controller. The Rossler system cannot only track any reference signal fast, but can synchronize with identical or different chaotic systems.

[Clinical analysis of 67 patients with brain metastases from breast cancer].

BACKGROUND & OBJECTIVE: The incidence of brain metastases from breast cancer seems to be increasing with the improvement of systemic control and survival prolongation. This study was to analyze the clinical characteristics, treatment modalities, and prognostic factors of brain metastases from breast cancer. METHODS: The time from primary diagnosis of breast cancer to brain metastases of 67 breast cancer patients were 0-15 years, and the median time was 2.5 years. Of the 67 patients, 3 received surgery plus radiotherapy, 30 received radiotherapy alone, 3 received chemotherapy alone, 26 received radiochemotherapy, and 5 received no treatment. Kaplan-Meier analysis and log-rank test were used to analyze survival status. RESULTS: Headache was the most common symptom of brain metastases from breast cancer. The median survival time was 4 years. After brain metastases, the median survival time was 11 months. Menstrual status, number of brain metastases, systemic metastases, and different treatment modalities had no correlations to survival time of the patients. CONCLUSIONS: The prognosis of brain metastases from breast cancer is still poor. Radiotherapy remains the standard treatment of brain metastases. The function of chemotherapy needs further study.

[Phase II clinical trial on China manufactured recombinant human interleukin-11 derivative in the prevention and treatment of chemotherapy-induced thrombocytopenia].

OBJECTIVE: This phase II clinical trial was designed to evaluate the efficacy and toxicity of recombinant human interleukin-11 (rhIL-11) derivative manufactured in China in the prevention and treatment of chemotherapy-induced thrombocytopenia in cancer patients. METHODS: A total of 100 cancer patients with chemotherapy-induced thrombocytopenia (< or = 75 x 10(9)/L) were studied by self-cross control. Ninty-one of them received 2 cycles of chemotherapy. In the first cycle (control cycle) the patients received chemotherapy only, while in the second cycle (treatment cycle), the patients were given subcutaneous injection of rhIL-11 derivative (40 microg.kg(-1).d(-1)) once daily after chemotherapy for 10 consecutive days or more until platelet count reached > or = 300 x 10(9)/L. RESULTS: 1. The patients with platelet count of < or = 75 x 10(9)/L was 89/89 in the control cycle and 44/89 in the treatment cycle (P = 0.00). The recovery time to the normal platelet count was 1-47 days (median 9 days) in the control cycle, and 1-18 days (median 5.5 days) in treatment cycle (P = 0.00). 2. Patients with platelet count of < or = 50 x 10(9)/L was 56/89 in the control cycle and 20/89 in the treatment cycle (P = 0.00). The recovery time to normal platelet count was 1-31 days (median 9 days) in the control cycle and 3-13 days (median 6 days) in the treatment cycle (P = 0.05). 3. The median nadir platelet count was 44 x 10(9)/L (range: 10 x 10(9)/L-75 x 10(9)/L) in the control cycle, and 83 x 10(9)/L (range: 10 x 10(9)/L-310 x 10(9)/L) in the treatment cycle (P = 0.00). The time of recovery to the normal platelet count was 1-31 days (median 6 days) in the control cycle, and 0-13 days (median 2 days) in the treatment cycle (P = 0.00). 4. Nine of 89 evaluable patients required platelet transfusion in the control cycle versus 1 of 89 patients in treatment cycle (P = 0.01), and the total platelet transfusion was 10 times in the control cycle versus once in the treatment cycle (P = 0.01). 5. The major adverse events associated with rhIL-11 derivative were: headache, fatigue, myalgia/arthralgia, edema and palpitation, etc. CONCLUSION: rhIL-11 derivative can be safely and effectively used for the prevention and treatment for chemotherapy-induced thrombocytopenia.