Optogenetic induction of caspase-8 mediated apoptosis by employing Arabidopsis cryptochrome 2.

Apoptosis, a programmed cell death mechanism, is a regulatory process controlling cell proliferation as cells undergo demise. Caspase-8 serves as a pivotal apoptosis-inducing factor that initiates the death receptor-mediated apoptosis pathway. In this investigation, we have devised an optogenetic method to swiftly modulate caspase-8 activation in response to blue light. The cornerstone of our optogenetic tool relies on the PHR domain of Arabidopsis thaliana cryptochrome 2, which self-oligomerizes upon exposure to blue light. In this study, we have developed two optogenetic approaches for rapidly controlling caspase-8 activation in response to blue light in cellular systems. The first strategy, denoted as Opto-Casp8-V1, entails the fusion expression of the Arabidopsis blue light receptor CRY2 N-terminal PHR domain with caspase-8. The second strategy, referred to as Opto-Casp8-V2, involves the independent fusion expression of caspase-8 with the PHR domain and the CRY2 blue light-interacting protein CIB1 N-terminal CIB1N. Upon induction with blue light, PHR undergoes aggregation, leading to caspase-8 aggregation. Additionally, the blue light-dependent interaction between PHR and CIB1N also results in caspase-8 aggregation. We have validated these strategies in both HEK293T and HeLa cells. The findings reveal that both strategies are capable of inducing apoptosis, with Opto-Casp8-V2 demonstrating significantly superior efficiency compared to Opto-Casp8-V1.

Experimental Studies on Thermal Oxidation and Laser Ignition Properties of Al-Mg-Li Powders.

Powder ramjets are a kind of vehicle propulsion system with high specific impulse and efficiency. They provide significant benefits in terms of extended propulsion and thrust adjustment. The pursuit of a highly reactive fuel appropriate for powder ramjets is likely to stimulate advancements in innovative propulsion systems, which are crucial for deep space exploration and long-term space missions. This work presents experimental studies on the thermal oxidation and laser ignition performance of aluminum-magnesium-lithium powders at atmospheric pressure. TG-DSC curves of powders in three heating rates were obtained. The ignition processes and ignition delay times were recorded by a CO2 laser ignition experiment system at a laser power of 10~60 W. The results show that at a lower heating rate of 10 K/min, the powder's thermal hysteresis is less, and the powder energy released in stage I is more concentrated. However, the degree of heat release concentration approached a similar level at heating rates of 30 K and 50 K. The ignition delay time decreased as the laser flux density increased. When the laser flux density exceeds 80 W/cm2, the effect of laser power on the ignition delay time decreases. At atmospheric pressure, the mathematical relationship between ignition delay time and laser flux density is given. Finally, the powder ignition processes at different laser powers are represented graphically.

[Clinical centralized safety monitoring and evaluation of traditional Chinese medicine formula granules].

Traditional Chinese medicine(TCM) formula granules are highly praised for the advanced, convenient, and modern use of Chinese medicinal materials. The safety of TCM formula granules has long been a concern of regulatory authorities and the medical industry. A multi-center, prospective, open, non-interventional, and centralized monitoring was carried out for the patients treated with TCM formula granules in 252 medical institutions from February 5, 2020 to April 19, 2022. All the case data and the incidence of adverse drug reactions/events were recorded. This study evaluated the safety of TCM formula granules, aiming to provide a reference for the clinically use. A total of 20 547 patients were included in this study. Four adverse events were recorded, including 3 adverse drug reactions with an adverse drug reaction rate of 0.015%, all of which occurred in the digestive system. There was no serious adverse event, and no factors related to adverse drug reactions/events were identified. The incidence of adverse drug reactions/events associated with China Resources Sanjiu Medical & Pharmaceutical Co., Ltd. TCM formula granules was rare, which proved their safety in clinical use. A comprehensive data mining and objective analysis was carried out for the medicines with high frequency in TCM formula granules, the commonly used medicine pairs and combinations, and departmental medication. The drug use characteristics, prescription rules, and departmental use of TCM formula granules were summarized, which can shed light on the prescription compatibility and clinical application.

Study on Mechanical Properties and Failure Mechanisms of Highly Filled Hydroxy-Terminated Polybutadiene Propellant under Different Tensile Loading Conditions.

To study the mechanical properties of highly filled hydroxy-terminated polybutadiene (HTPB) propellant with 90 wt% solid fillers, the stress-strain curves of the propellant under different temperatures (-50 to 70 °C) and strain rates (0.000476 to 0.119048 s-1) were obtained by uniaxial tensile test. Moreover, to obtain the glass transition temperature and understand the effect of low temperatures on the mechanical properties of the propellant, DMA experiments were carried out. On this basis, the mechanical response laws of the propellant were analyzed, and the master curves of mechanical properties were established. Furthermore, the fracture features of the propellant under typical loading conditions were obtained by SEM, and the corresponding failure mechanisms were analyzed. The results show that the maximum strength decreases with increasing temperature, while the maximum elongation increases with increasing temperature at the same strain rate. The maximum tensile strength increases with increasing strain rate, while the maximum elongation decreases with increasing strain rate at the same temperature. The maximum tensile strength is lowest with a value of 0.35 MPa when the temperature is 343.15 K and the strain rate is 0.000476 s-1, at which time the maximum elongation reaches the highest with a value of 44%. In terms of failure mechanisms, the propellant shows no particle fracture, and the failure modes of the propellant are mainly matrix tearing and dewetting.

Experimental and Numerical Investigation into the Mechanical Behavior of Composite Solid Propellants Subject to Uniaxial Tension.

To further explore the quasi-static mechanical characteristics of composite solid propellants at low strain rates, an investigation was conducted on the mechanical behavior and damage mechanisms of a four-component hydroxy-terminated polybutadiene (HTPB) propellant by means of experiments and numerical simulation. A uniaxial tensile test and scanning electron microscope (SEM) characterization experiment were carried out. A microstructural model, which accurately represents the mesoscopic structure, was developed via the integration of micro-CT scanning and image-processing techniques. The constructed microstructural model was utilized to conduct a numerical simulation of the mechanical behavior. The experimental results demonstrated that the maximum tensile strength increases with increasing strain rate, and the primary cause of propellant failure at low strain rates is the dewetting phenomenon occurring at the interface between the larger particles and the matrix. The maximum tensile strength is 0.48 MPa when the strain rate is 0.00119 s-1, and the maximum tensile strength is 0.37 MPa when the strain rate is 0.000119 s-1. The simulation results indicated a consistent trend in variation when comparing the simulation and experimental curves. This suggested that the established model exhibits a high level of reliability, and provides a promising approach for carrying out microstructural simulations of heterogeneous propellants in future. The mechanical behavior of the propellant can be effectively described by utilizing a mesoscopic finite element model that incorporates the superelastic constitutive model of the matrix and the bilinear cohesive model. This framework facilitates the representation of mesoscopic damage evolution, which consequently provides insights into the damage mechanism. Additionally, the utilization of such models assists in compensating for the limitations of damage evolution characterization experiments.

Identification of signature of tumor-infiltrating CD8 T lymphocytes in prognosis and immunotherapy of colon cancer by machine learning.

BACKGROUND: To explore the specific marker of CD8+ T cell subsets which are closely related to the prognosis and immunotherapy of patients with colon cancer. METHODS: 18 kinds of immune cell expression profile data sets were obtained from GEO database. Compared with other immune cell types, the specific markers of CD8 (+) T cells (TI-CD8) in colorectal cancer were screened. Regression analyses were used to further screen prognostic related genes and construct a prognostic evaluation model. The patients were stratified and analyzed according to the risk scores, KRAS mutation status, stage, lymphatic infiltration and other indicators. The landscape of infiltration level, mutation and copy number variation of immune subsets in high and low TI-CD8Sig score groups were compared and analyzed. The difference of drug response between high and low TI-CD8Sig score groups was analyzed. Differential expression of the model genes was verified by the HPA database. RESULTS: Six prognostic-related CD8T cell-specific gene targets were further screened, and the prognostic evaluation model was constructed. The AUC value of the model is >0.75. FAT3 and UNC13C showed a high mutation state in the low-risk group, while USH2A, MUC5B et al. specifically showed a high mutation state in the high-risk group. Compared with the low-risk group, the high-risk group had lower effective rate of drug response. The expression of PD-1 gene was positively correlated with the level of TI-CD8Sig score. CONCLUSION: The risk assessment model based on CD8T cell-specific marker genes can effectively predict the prognosis and the drug response of patients with CRC.

Innovation policy and ecological welfare performance: evidence from a quasi-natural experiment of China.

The National Innovative City Pilot Policy (NICPP) is a policy implemented by the Chinese government to create an environment conducive to innovation, optimize industrial structure, promote economic development, and stimulate green innovation. The impact of this policy on ecological welfare performance is a question worth exploring. Based on panel data from 285 cities from 2007 to 2021, this paper uses the multi-period difference-in-difference (DID) model, propensity score matching method, and spatial DID model to study the impact of NICPP on ecological welfare performance and spatial spillover effects. The results show that (1) NICPP can significantly improve ecological welfare performance. (2) The mechanism analysis found that NICPP mainly improves ecological welfare performance through technological innovation investment, industrial structure upgrading, and increasing government attention. (3) The heterogeneity analysis found that NICPP has a more substantial driving effect on the ecological welfare development of cities in the eastern and western regions, cities with higher administrative levels, and cities with lower secondary industry agglomeration. (4) Further research has found that NICPP not only promotes the development of local ecological welfare but also has a positive spatial spillover effect on the ecological welfare performance of neighboring regions. This paper enriches the research on the effects of NICPP and provides policy references for the sustainable development of cities.

A rapid screening platform for antibiotic susceptibility testing based on a simple colorimetric method.

Rapid screening platforms for antibiotic susceptibility testing (AST) are important in inhibiting bacterial resistance in clinical practice. Herein, a rapid screening platform is reported for AST, which is based on nanofiber membrane enrichment bacteria-assisted cell counting Kit-8 (CCK8) colorimetry. The absorbance of CCK8 formazan has a linear relationship with the number of bacteria. The interference of antibiotics in the absorbance of CCK8 formazan could be eliminated by separating planktonic bacteria from the culture medium using nanofiber membranes. The total detection time is 7-9 h, using the new screening platform, which is significantly shorter than that with the traditional method, and the limit of detection of this method is 10 CFU mL-1. The evaluation results of antibiotic susceptibility are identical when using the new screening method and traditional methods. This method meets the definition of "rapid testing" for antibiotic susceptibility by most microbiologists. Furthermore, the new screening platform for antibiotic susceptibility testing ability in vitro was proved using E. coli in urine and blood, and S. aureus in wound fluid as practical samples. All the results showed that the new screening platform is a promising method for rapid antibiotic susceptibility testing in vitro.

Application of nanotechnology in thrombus therapy.

The diseases caused by two pathological processes, thrombosis, and thromboembolism, are clinically known as thrombotic diseases, which seriously threaten human life and health, and their incidence rate is the highest among various diseases. Research on thrombotic diseases is one of the focuses and hotspots of contemporary medical research. Nanomedicine is a new branch of nanotechnology used in the medical field, and nanomaterials are widely used in medical imaging and drug delivery to help diagnose and treat major diseases such as cancer. With the gradual maturity of nanotechnology, new nanomaterials have recently been used in antithrombotic drugs and released accurately at lesions, which has improved antithrombotic therapy safety. Nanosystems can be employed for cardiovascular diagnosis in future as they can aid in diagnosing pathological diseases and treat them with targeted delivery systems. Unlike other reviews, we herein aim to illustrate the progress of nanosystems in thrombosis therapy. This paper mainly describes how a drug-loaded nanosystem can control drug release under various conditions and accurately treat thrombus, summarizing the research progress of nanotechnology in antithrombotic therapy so that clinicians can better understand nanotechnology and its applications and provide new ideas for treating thrombosis.

Robust Visual Odometry Leveraging Mixture of Manhattan Frames in Indoor Environments.

We propose a robust RGB-Depth (RGB-D) Visual Odometry (VO) system to improve the localization performance of indoor scenes by using geometric features, including point and line features. Previous VO/Simultaneous Localization and Mapping (SLAM) algorithms estimate the low-drift camera poses with the Manhattan World (MW)/Atlanta World (AW) assumption, which limits the applications of such systems. In this paper, we divide the indoor environments into two different scenes: MW and non-MW scenes. The Manhattan scenes are modeled as a Mixture of Manhattan Frames, in which each Manhattan Frame in itself defines a Manhattan World of a specific orientation. Moreover, we provide a method to detect Manhattan Frames (MFs) using the dominant directions extracted from the parallel lines. Our approach is designed with lower computational complexity than existing techniques using planes to detect Manhattan Frame (MF). For MW scenes, we separately estimate rotational and translational motion. A novel method is proposed to estimate the drift-free rotation using MF observations, unit direction vectors of lines, and surface normal vectors. Then, the translation part is recovered from point-line tracking. In non-MW scenes, the tracked and matched dominant directions are combined with the point and line features to estimate the full 6 degree of freedom (DoF) camera poses. Additionally, we exploit the rotation constraints generated from the multi-view dominant directions observations. The constraints are combined with the reprojection errors of points and lines to refine the camera pose through local map bundle adjustment. Evaluations on both synthesized and real-world datasets demonstrate that our approach outperforms state-of-the-art methods. On synthesized datasets, average localization accuracy is 1.5 cm, which is equivalent to state-of-the-art methods. On real-world datasets, the average localization accuracy is 1.7 cm, which outperforms the state-of-the-art methods by 43%. Our time consumption is reduced by 36%.

Impact of globalization on the environment in major CO2-emitting countries: Evidence using bootstrap ARDL with a Fourier function.

Alongside sustainable development as a major global aim, the contribution made by globalization to environmental issues has become crucial in recent decades. Prior studies have focused on how trade in globalization influences the environment. However, multiple economic, social, and political factors are also important, the integration of which needs to be considered in sustainable development. Sharp and smooth breaks in time series models are the consequence of real-world structures. Using the bootstrap autoregressive-distributed lag test with a Fourier function, the present study reexamined the nexus between globalization and the environment in China, the United States, and India. The empirical results indicate that in the United States, the nexus between globalization and the environment is cointegrated in the long-term. In the short term, globalization is improving the environment in the United States and India. However, in China, globalization is resulting in environmental degradation. This research will assist policymakers in developing comprehensive strategies for sustainable development.

Transportation, Environmental Degradation, and Health Dynamics in the United States and China: Evidence From Bootstrap ARDL With a Fourier Function.

Transportation and environmental degradation, with indirect and direct effects, play a significant role in determining the health of a nation's citizens. This study uses bootstrap ARDL with a Fourier function to examine transportation, environmental degradation, and health dynamics in the United States and China. In the long run, the results support the cointegration relationship between transportation, environmental degradation, and health in both countries. The results show the contingency of the causality where a negative impact of transportation on environmental degradation exists in the United States while a positive impact exists in China. The effect of environmental degradation on health is negative in the United States while a positive effect exists in China. Regarding the causal direction between the variables of interest, the implications provide policymakers in developing strategy and policy for sustainable development.

m6A Regulator-Based Methylation Modification Patterns Characterized by Distinct Tumor Microenvironment Immune Profiles in Rectal Cancer.

Background: Previous studies reported the related role of RNA n6-methyladenosine (m6A) modification in tumorigenesis and development. However, it is not clear whether m6A modification also plays a potential role in the immune regulation of rectal cancer (RC) and the formation of tumor microenvironment. Methods: In this study, we screened 23 m6A regulatory factors from 369 rectal cancer specimens, further determined the modification patterns of m6A in RC, and systematically linked these modification patterns with the characteristics of TME cell infiltration. The principal component analysis (PCA) algorithm was used to evaluate the m6A modification pattern of a single tumor related to immune response. Results: Three different m6A modification patterns were found in the measurement results, which are related to different clinical results and biological pathways. TME identification results show that the identified m6A pattern is closely related to immune characteristics. According to the m6Ascore extracted from m6A-related signature genes, RC patients were divided into high and low score subgroups combined with tumor mutation burden. Patients with high tumor mutation burden and higher m6Ascore have a significant survival advantage and enhanced immune infiltration. Further analysis showed that patients with higher m6Ascore had higher PD-L1 expression levels and showed better immune response and lasting clinical benefits. Conclusions: M6A modification plays a crucial role in the formation of TME diversity and complexity. The evaluation of the m6A modification mode will help us to enhance our understanding of the characteristics of TME infiltration and provide new insights for more effective immunotherapy strategies.

Research on financing strategy of low-carbon supply chain based on cost-sharing contract.

The paper considers a low-carbon supply chain which consists of a capital constrained manufacturer and a retailer. We consider the retailer takes part in low-carbon cost sharing when the manufacturer faces capital constraints due to increasing investment in low-carbon production technologies. We further construct and analyze the performance of the supply chain under three financing strategies: capital constraint without financing (NF), trade credit financing (TCF), and bank credit financing (BCF). Our model provides a financing decision-making model for a low-carbon supply chain with capital constraints, and we design a cost-sharing contract can coordinate supply chain and strengthen the cooperation between enterprises. Moreover, through numerically analyzing the impact of cost-sharing ratio, low carbon preference coefficient of consumers, and interest rate on supply chain decisions and profits, we find (i) the profit of low-carbon supply chain members with capital constrain under TCF strategy is always better than BCF strategy; (ii) cost-sharing contract can increase the profit of the manufacturer and the retailer; and (iii) the low carbon preference coefficient of consumers is also a positive factor in the optimal profit of the manufacturer and retailer.

Measuring the Impact of Health on Economic Growth Using Pooling Data in Regions of Asia: Evidence From a Quantile-On-Quantile Analysis.

Health improvement has become a significant social priority since a moderately good human capital condition improves the workforce's abilities, efficiency, and quality of life. A rapid increase in healthcare expenditure is a trend in major developing and developed countries; however, healthcare expenditure widely varies among most Asian countries. Asian countries contribute a significant amount of output to economic development worldwide. The statistical test power is more efficient for the pooling of national data than individual national data because of the economic value and trade integration of regional nations. This is the first study that applies the quantile-on-quantile approach to investigate the influence of the quantiles of healthcare on the quantiles of the economy's growth for pooling forty countries in the Asian region. As the quantile of healthcare expenditure increases in the countries, the impact of healthcare expenditure on the economy's growth does not guarantee an increase. The positive and negative effects of healthcare expenditure on developing the economic relationship will repeatedly occur when the quantiles of the economy's growth increase in the countries. One implication is that the governments should account for problems such as corruption, bureaucracy, underinvestment, and inefficiency in health-related resource utilization.

Overexpressed LINC00467 promotes the viability and proliferation yet inhibits apoptosis of gastric cancer cells via raising ITGB3 level.

Long non-coding RNA (lncRNA) LINC00467 plays a proto-oncogenic role in non-small cell lung cancer. However, its effect and modulatory mechanism in gastric cancer (GC) are unknown. Thereby, we elucidated the mechanism of LINC00467 in GC. LINC00467 level in GC tissues was assessed by bioinformatic analysis, and clinicopathological parameters from GC patients were collected. The levels of LINC00467, integrin subunit beta 3 (ITGB3), proliferating cell nuclear antigen (PCNA), cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase 1 (PARP1) in tissue samples or treated GC cells were assessed by quantitative real-time polymerase chain reaction (qRT-PCR), fluorescence in situ hybridization (FISH), or Western blot. The viability, proliferation and apoptosis of GC cells were detected by methyl thiazolyl tetrazolium assay, colony formation assay, and flow cytometry. Levels of LINC00467 and ITGB3 were up-regulated in GC, and highly expressed LINC00467 was positively associated with tumor size, differentiation, N stage, and T stage in GC patients. LINC00467 was enriched in cytoplasm of GC cells, and overexpressed LINC00467 promoted the viability and proliferation as well as levels of ITGB3 and PCNA, while suppressing the apoptosis and levels of cleaved caspase-3 and cleaved PARP1 in GC cells. Besides, the effects of shLINC00467 on inhibiting cell viability, proliferation of GC cells and PCNA level and promoting apoptosis as well as levels of cleaved caspase-3 and cleaved PARP1 were all partially reversed by overexpressed ITGB3. Overexpressed LINC00467 enhanced the viability and proliferation but inhibited apoptosis of GC cells via increasing ITGB3 level.

Using single-cell sequencing technology to detect circulating tumor cells in solid tumors.

Circulating tumor cells are tumor cells with high vitality and high metastatic potential that invade and shed into the peripheral blood from primary solid tumors or metastatic foci. Due to the heterogeneity of tumors, it is difficult for high-throughput sequencing analysis of tumor tissues to find the genomic characteristics of low-abundance tumor stem cells. Single-cell sequencing of circulating tumor cells avoids interference from tumor heterogeneity by comparing the differences between single-cell genomes, transcriptomes, and epigenetic groups among circulating tumor cells, primary and metastatic tumors, and metastatic lymph nodes in patients' peripheral blood, providing a new perspective for understanding the biological process of tumors. This article describes the identification, biological characteristics, and single-cell genome-wide variation in circulating tumor cells and summarizes the application of single-cell sequencing technology to tumor typing, metastasis analysis, progression detection, and adjuvant therapy.

Patient safety in Work Environments: Perceptions of Pediatric Healthcare Providers in Taiwan.

BACKGROUND: Extensive research on the link between the organizational characteristics of the work environment and patient safety in a healthcare organization has been conducted; yet, only a few studies have concentrated on care providers in a pediatric unit. OBJECTIVES: To determine the correlation between different work environment factors impacting patient safety in a pediatric care unit from the perspective of registered nurses working in these units. DESIGN: Cross-sectional design. DATA SOURCES AND METHODS: The study was conducted with 155 registered nurses from a pediatric unit in a medical center in Taiwan with the Chinese version of the Safety Attitudes Questionnaire (SAQ) 2014-2017. RESULTS: Teamwork climate, higher job satisfaction, and better working conditions are linked to positive perceptions of patient safety culture. Emotional exhaustion is negatively related to most dimensions of patient safety. CONCLUSION: Teamwork climate, job satisfaction, working conditions, and emotional exhaustion were identified as critical factors impacting the patient safety climate. IMPLICATIONS FOR NURSING OR HEALTH POLICY: Investments to improve teamwork climate, job satisfaction, and working conditions and reduce emotional exhaustion may have a positive effect on patient safety in pediatric care units.