JAK/STAT signaling regulated intestinal regeneration defends insect pests against pore-forming toxins produced by Bacillus thuringiensis.

A variety of coordinated host-cell responses are activated as defense mechanisms against pore-forming toxins (PFTs). Bacillus thuringiensis (Bt) is a worldwide used biopesticide whose efficacy and precise application methods limits its use to replace synthetic pesticides in agricultural settings. Here, we analyzed the intestinal defense mechanisms of two lepidopteran insect pests after intoxication with sublethal dose of Bt PFTs to find out potential functional genes. We show that larval intestinal epithelium was initially damaged by the PFTs and that larval survival was observed after intestinal epithelium regeneration. Further analyses showed that the intestinal regeneration caused by Cry9A protein is regulated through c-Jun NH (2) terminal kinase (JNK) and Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. JAK/STAT signaling regulates intestinal regeneration through proliferation and differentiation of intestinal stem cells to defend three different Bt proteins including Cry9A, Cry1F or Vip3A in both insect pests, Chilo suppressalis and Spodoptera frugiperda. Consequently, a nano-biopesticide was designed to improve pesticidal efficacy based on the combination of Stat double stranded RNA (dsRNA)-nanoparticles and Bt strain. This formulation controlled insect pests with better effect suggesting its potential use to reduce the use of synthetic pesticides in agricultural settings for pest control.

A deep learning model to identify gene expression level using cobinding transcription factor signals.

Gene expression is directly controlled by transcription factors (TFs) in a complex combination manner. It remains a challenging task to systematically infer how the cooperative binding of TFs drives gene activity. Here, we quantitatively analyzed the correlation between TFs and surveyed the TF interaction networks associated with gene expression in GM12878 and K562 cell lines. We identified six TF modules associated with gene expression in each cell line. Furthermore, according to the enrichment characteristics of TFs in these TF modules around a target gene, a convolutional neural network model, called TFCNN, was constructed to identify gene expression level. Results showed that the TFCNN model achieved a good prediction performance for gene expression. The average of the area under receiver operating characteristics curve (AUC) can reach up to 0.975 and 0.976, respectively in GM12878 and K562 cell lines. By comparison, we found that the TFCNN model outperformed the prediction models based on SVM and LDA. This is due to the TFCNN model could better extract the combinatorial interaction among TFs. Further analysis indicated that the abundant binding of regulatory TFs dominates expression of target genes, while the cooperative interaction between TFs has a subtle regulatory effects. And gene expression could be regulated by different TF combinations in a nonlinear way. These results are helpful for deciphering the mechanism of TF combination regulating gene expression.

Involucrasin B Inhibits the Proliferation of Caco-2 Cells by Regulating the TGFß/SMAD2-3-4 Pathway.

(1) Background: Colorectal cancer (CRC) is the third most common malignant tumor worldwide and the second most common cause of cancer death. However, effective anti-CRC drugs are still lacking in clinical settings. This article investigated the anti-proliferative effect of involucrasin B on CRC Caco-2 cells. (2) Methods: This study employed a sulforhodamine B (SRB) method, colony formation experiments, flow cytometry, FastFUCCI assay, dual luciferase assay, and Western blot analysis for the investigation. (3) Results: The SRB method and colony formation experiments showed that involucrasin B exhibited an inhibitory effect on the Caco-2 cells cultured in vitro. Subsequently, the flow cytometry, FastFUCCI assay, and Western blotting results showed that involucrasin B induced cell cycle arrest in the G1 phase dose-dependently. Involucrasin B significantly enhanced the TGFß RII protein level and SMAD3 phosphorylation, thus inhibiting the expression of CDK4 and cyclin D1 and causing G1 cell cycle arrest. (4) Conclusion: This study shows that involucrasin B exerts its anti-proliferative effect by regulating the TGFß/SMAD2-3-4 pathway to cause G1 cycle arrest in Caco-2 cells.

Strong Interface Construction of Carbon Fiber-reinforced PEEK Composites: An Efficient Method for Modifying Carbon Fiber with Crystalline PEEK.

In order to improve the poor solvent resistance and poor temperature resistance caused by traditional sizing agents, crystalline poly(ether ether ketone) (PEEK) is introduced to the interfacial phases of carbon fiber (CF) reinforced PEEK composites by a soluble precursor named PEEK-1,3-dioxolane. By changing the soluble precursor molecular weight and concentration in the sizing solution, the content of PEEK coated on the CF fiber surface can be controlled and the different interfacial properties of the PEEK composites can be obtained. The results shows that, with this method, crystalline PEEK can be completely coated on the CF surface, and the interfacial shear strength of the PEEK composites increases from 43.42 to 83.13 MPa. Due to none of any soluble compounds in the PEEK composites, the interfacial layer is well preserved under organic solvents and hygrothermal conditions, and the interfacial shear strength (IFSS) of the PEEK composites maintained above 85.4% and 90.44%, respectively. Scanning electron microscope clarifies that the mechanism of interface enhancement comes from a better wetting of crystalline PEEK on the fiber surface. Additionally, the sizing system of this investagation has the potential commercial value because of no toxic reagent (such as 2,4,5-trichloro-1-hydroxy-benzene or concentrated sulfuric acid) is required during sizing.

Effect of physical exercise on young anesthesiologists with on-call-related fatigue.

To explore whether exercise can effectively relieve the fatigue state of overnight shift anesthesiologists with chronic fatigue. 78 anesthesiologists between 30 and 40 years of age at four hospitals in China were analyzed in the investigation. The Profile of Mood States (POMS) and Chalder Fatigue Scale (CFS) were used to assess psychological symptoms and fatigue respectively, and data regarding demographics, health, exercise and work-related variables were also collected. The total and physical fatigue score were highest among those who seldom do exercise compared to those who always do exercise (p < .05, respectively). Moreover, anesthesiologists who exercised 30-60 min everyday had the lowest total and physical fatigue score. When exercise for more than 60 min, the total and physical fatigue scores then increased. After completing a night shift, the post-on-call total Profile of Mood States scores of those who seldom do exercise was significantly increased (t = -4.9, p < .001). These study findings suggested that regular exercise 30-60 min everyday could effectively reduce anesthesiologists' physical fatigue and decrease their negative psychological state, and anesthesiologists should positively adjust working and exercise time.

[Effect of Transcutaneous Acupoint Electrical Stimulation on Propofol Usage in Closed-loop Anes- thesia Delivery System in Pediatric Cardiac Surgery].

Objective To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) on propofol usage in closed-loop anesthesia delivery system and pediatric hemodynamics. Methods Sixty children patients undergoing selective tonsillectomy and adenoidectomy surgeries were randomly allocated to the TEAS group (T) and the control group (C) , 30 in each group. Anesthesia maintenance in both groups was performed by propofol closed-loop anesthesia infusion system after induction of anesthesia. Patients in group T were treated with continuous TEAS (2/100 Hz sparsedense wave, 8 - 12 mA) at unilateral Hegu (L14) and Shenmen till the end of surgery. No TEAS was performed to patients in group C. Mean arterial pressure (MAP) and heart rate (HR) were recorded before anesthesia (TO), immediately after intubation ( T1) , 5 min after intubation (T2) , 10 min after intubation (T3) , 15 min after intubation (T4) , the time for intubation (T5) , respectively. The total dose of propofol, times for propofol dose adjustment, average target concentration, cases of patients with extra Fentanyl were recorded during anesthesia maintenance. Bispectral index (BIS) was recorded. Pediatric Anesthesia Emergence Delirium (PAED) scale and Modified Children's Hospital of Eastern Ontario Pain Scale (MCHEOPS) were assessed at T5, 5 min after extubation (T6) , 10 min after extubation (T7) , 15 min after extubation (T8), 30 min after extubation (T9) , respectively. Epinephrine (NE) was measured at TO, T1, T5, and T9, concentrations of IL-1 and IL-6 were measured at TO, T5, 24 h after surgery ( T10) , 48 h after surgery (T11), respectively. Results Compared with group C, MAP at T4 and T5 and HR at T1-T5 all de- creased, PAED scale and MCHEOPS decreased at T5-T9, NE concentrations were significantly reduced at T5 and T9, concentrations of IL-1 and IL-6 decreased at T5, T10, T1 1 in group T (P <0. 05, P <0. 01). Compared with group C, the total dose of propofol, times for propofol dose adjustment, average target concentration were reduced in group T during surgery (P <0. 05, P <0. 01). Twenty cases (67%) used propofol in group C and 9 cases (30% ) used propofol in group T during surgery, with statistical difference (P <0. 01). Changes of BIS was not statistically different between the two groups (P >0. 05). Conclusion TEAS could inhibit stress response and inflammatory response of children patients, stabilize their hemo- dynamics during surgery, thereby reducing propofol dose in closed-loop anesthesia delivery system.

Calpain as a Therapeutic Target for Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a complex pathophysiological process with multiple links and factors. It involves the interaction of inflammation, oxidative stress, and glucose metabolism, and results in acute and even long-term brain damage and impairment of brain function. Calpain is a family of Ca2+-dependent cysteine proteases that regulate cellular function. Calpain activation is involved in cerebral ischemic injury, and this involvement is achieved by the interaction among Ca2+, substrates, organelles, and multiple proteases in the neuronal necrosis and apoptosis pathways after cerebral ischemia. Many calpain inhibitors have been developed and tested in the biochemical and biomedical fields. This study reviewed the potential role of calpain in the treatment of HIE and related mechanism, providing new insights for future research on HIE.

Bacillus thuringiensis Cry9Aa Insecticidal Protein Domain I Helices α3 and α4 Are Two Core Regions Involved in Oligomerization and Toxicity.

Bacillus thuringiensis Cry9 proteins show high insecticidal activity against different lepidopteran pests. Cry9 could be a valuable alternative to Cry1 proteins because it showed a synergistic effect with no cross-resistance. However, the pore-formation region of the Cry9 proteins is still unclear. In this study, nine mutations of certain Cry9Aa helices α3 and α4 residues resulted in a complete loss of insecticidal activity against the rice pest Chilo suppressalis; however, the protein stability and receptor binding ability of these mutants were not affected. Among these mutants, Cry9Aa-D121R, Cry9Aa-D125R, Cry9Aa-D163R, Cry9Aa-E165R, and Cry9Aa-D167R are unable to form oligomers in vitro, while the oligomers formed by Cry9Aa-R156D, Cry9Aa-R158D, and Cry9Aa-R160D are unstable and failed to insert into the membrane. These data confirmed that helices α3 and α4 of Cry9Aa are involved in oligomerization, membrane insertion, and toxicity. The knowledge of Cry9 pore-forming action may promote its application as an alternative to Cry1 insecticidal proteins.

Correlation analysis between camrelizumab trough concentration levels and efficacy or safety in East Asian patients with advanced lung cancer.

BACKGROUND: Camrelizumab combined with chemotherapy is approved across tumor types. However, only a fraction of patients benefits from immunotherapy, and biomarkers such as the expression of PD-L1, tumor mutational burden, and CXCL11 are expensive and suboptimal specificity for cancer patients. An exposure-response (E-R) relationship has been reported in many immune checkpoint inhibitors (ICIs), and the trough concentrations and other drug exposure metrics are broadly used to guide dosing decisions, assess exposure-outcomes relationships, and ultimately predict outcomes based on those relationships. However, the potential use of trough concentration levels for camrelizumab is still not clear. METHODS: Blood samples were obtained at trough levels after doses 3 and 4 from 77 patients with advanced lung cancer who received camrelizumab (200 mg Q3 W) monotherapy or combined with chemotherapy. We optimized a competitive ELISA method to measure the trough concentration. RESULTS: We found that the trough concentration was steady after 3 dose cycles, and the trough concentration level of camrelizumab was higher in patients who developed immune-related adverse effects (irAEs) than in those who did not (P < 0.05) but was not observed in disease progression and PFS (P > 0.05). Age (< 65 years old), no smoking history, and efficacy evaluation after 4-dose treatment were associated with PFS (P < 0.05), but no significance was observed in other clinical characteristics. Total bilirubin and albumin had an influence on trough concentration, and monocytes and albumin were independent risk factors for PFS (P < 0.05). CONCLUSIONS: Our results suggest that the trough concentration level of camrelizumab might be a risk factor for the occurrence of irAEs in advanced lung cancer, and using the immunotherapy as early as possible may bring better clinical outcomes.

Study on the Preparation and Process Parameter-Mechanical Property Relationships of Carbon Fiber Fabric Reinforced Poly(Ether Ether Ketone) Thermoplastic Composites.

Carbon fiber fabric-reinforced poly(ether ether ketone) (CFF-PEEK) composites exhibit exceptional mechanical properties, and their flexibility and conformability make them a promising alternative to traditional prepregs. However, the formation of the CFF-PEEK composite is trapped in the high viscosity of PEEK, the smooth surface, and tightly interwoven bundles of CFF. It is more difficult for the resin to flow through the fibers of complex textile structures. Here, a simple film stacking method using the hot-pressing process of plain-woven CFF-PEEK thermoplastic composites is discussed. The uniform distribution of PEEK resin between each layer of CFF reduces the flow distance during the molding process, preventing defects in the composite material effectively. Four process parameters, including molding temperature (370, 385, 400, and 415 °C), molding pressure (1, 2, 4, 8, and 10 MPa), molding time (10, 20, 30, 40, 60, and 90 min), and pre-compaction process, are considered. Interlaminar shear strength (ILSS), tensile strength, and flexural strength of CFF/PEEK composites are evaluated to optimize the process parameters. Moreover, ultrasonic scanning microscopy and scanning electron microscopy are employed to observe the formation quality and microscopic failure modes of CFF/PEEK composites, respectively. The ultimate process parameters are a molding temperature of 410 °C, molding pressure of 10 MPa, molding time of 60 min, and the need for the pre-compaction process. Under the best process parameters, the ILSS is 62.5 MPa, the flexural strength is 754.4 MPa, and the tensile strength is 796.1 MPa. This work provides valuable insight for studying the process parameters of fiber fabric-reinforced thermoplastic polymer composites and revealing their impact on mechanical properties.

Multi-layered e-feedback anxiety: An action research study among Chinese learners using peer feedback activities in an academic writing course.

There is a gradual increase in the use of e-feedback in higher education, but issues regarding learners' anxiety remain unresolved. In light of the learners' anxiety, e-feedback would essentially become a formality if they are not proactive in providing constructive feedback. This action research examines three cycles of e-feedback activities performed by 12 doctoral students in an academic writing course in a public university in Macau, China. Specifically, the e-feedback activity involved a comprehensive use of various new educational technology tools, namely Moodle, WeChat and Rain Classroom. This study reveals that the causes of students' anxiety when using e-feedback are multi-layered, mainly from the use of smartphones as a communication medium for conducting formal learning activities and the lack of interpersonal and English skills for conveying their thoughts when providing e-feedback. The traditional Chinese culture about the importance of "face" and interpersonal harmony also has impacts on learners' e-feedback delivery. These findings shed new lights on pedagogical practice in higher education.

Insurer Market Power And Hospital Prices In The US.

The extent to which concentration in the health insurance market affects negotiated prices paid to hospitals is of high interest to policy makers. We examined the association between insurer market share and hospital prices, using a new source of data obtained through the federal Hospital Price Transparency initiative. We found that the market-leading insurer in the least competitive (most concentrated) insurance markets pays 15 percent less to hospitals than the market-leading insurer in the most competitive (least concentrated) markets. We also found the price relationship to be more pronounced for for-profit hospitals than for not-for-profit hospitals. Our results invite the question of whether dominant insurers are passing savings on to employers in the form of lower premiums.

Psychometric evaluation of the academic involution scale for college students in China: An application of Rasch analysis.

Recent academic attention on educational involution in China underpins the need for a valid and reliable instrument to precisely measure college students' academic involution behaviors. Seeing the scarcity of a proper instrument, the current study attempted to analyze the item-level psychometric properties of the newly developed Academic Involution Scale for College Students (AISCS) in China by using a Rasch model. A total of 637 college students in a public university in northern China participated in the study. Data were examined with respect to unidimensionality, rating scale functioning, item fit statistics, item polarity, item- and person-level reliability and separation, item hierarchy and invariance across educational background with Winsteps. The results show that AISCS was a single unidimensional construct with good psychometric properties. Although two items demonstrated differential item functioning, it is plausible given the differences between assessment methods for undergraduates and postgraduates. Limitations and future research directions with regard to sample selection, inclusion of more validity evidence and adding prospective additional academic involution were discussed.

Inhibition of YAP by lenvatinib in endothelial cells increases blood pressure through ferroptosis.

Lenvatinib, a multitarget tyrosine kinase inhibitor (TKI), increases the incidence of severe hypertension and thus the incidence of cardiovascular complications. Inhibition of ferroptosis, a newly recognized type of cell death, alleviates endothelial dysfunction. Here, we report that lenvatinib-induced hypertension is associated with ferroptosis of endothelial cells. RNA sequencing (RNA-seq) showed that lenvatinib led to ferroptosis of endothelial cells and that administration of mouse with ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, dramatically ameliorated lenvatinib-induced hypertension and reversed lenvatinib-induced impairment of endothelium-dependent relaxation (EDR). Furthermore, lenvatinib significantly reduced glutathione peroxidase 4 (GPX4) expressions in the mouse aorta and human umbilical vein endothelial cells (HUVECs) and increased lipid peroxidation, lactate dehydrogenase (LDH) release, and malondialdehyde (MDA) levels in HUVECs. Immunofluorescence and Western blotting showed that lenvatinib significantly reduced Yes-associated protein (YAP) nuclear translocation but not cytoplasmic YAP expression in HUVECs. The data, generated from both in vivo and in vitro, showed that lenvatinib reduced total YAP (t-YAP) expression and increased the phosphorylation of YAP at both Ser127 and Ser397, without affecting YAP mRNA levels in HUVECs. XMU-MP-1 mediated YAP activation or YAP overexpression effectively attenuated the lenvatinib-induced decrease in GPX4 expression and increases in LDH release and MDA levels. In addition, overexpression of YAP in HUVECs ameliorated lenvatinib-induced decrease in the mRNA and protein levels of spermidine/spermine N (1)-acetyltransferase-1 (SAT1), heme oxygenase-1 (HO-1), and ferritin heavy chain 1 (FTH1). Taken together, our data suggest that lenvatinib-induced inhibition of YAP led to ferroptosis of endothelial cells and subsequently resulted in vascular dysfunction and hypertension.

Social relationships and grit in English as a foreign language learning among high school students: A three-wave longitudinal study.

This study examined the longitudinal reciprocal relations between students' grit and their perceptions of social relationships (teacher-student and peer relationships) in studying English as a foreign language (EFL). A total of 2,435 students from Grades 10-11 in China (Mage = 16.40 years old, 54.2% female) participated in the study on three occasions across 1 year. The three-wave cross-lagged analytic model results indicated that (a) peer relationship and grit reciprocally enhanced each other across both intervals; (b) the teacher-student relationship at Time 2 was influenced by Time 1 grit, but not vice versa. Nevertheless, the teacher-student relationship transactionally facilitated each other during the second interval (from Time 2 to Time 3). The multiple-group confirmatory factor analysis (MG-CFA) results indicated that such relations remained stable across gender. The study's findings contribute to ongoing research delineating the dynamic system between social relationships and grit in EFL learning. It also reveals that males and females benefit similarly during social communications with peers and their English language teachers. Implications for educational practices were discussed.

Application of transcranial Doppler in cerebrovascular diseases.

Transcranial Doppler (TCD) is a rapid and non-invasive diagnostic technique that can provide real-time measurements of the relative changes in cerebral blood velocity (CBV). Therefore, TCD is a useful tool in the diagnosis and treatment of clinical cerebrovascular diseases (CVDs). In this review, the basic principles of TCD and its application in CVD were outlined. Specifically, TCD could be applied to evaluate occlusive CVD, assess collateral circulation in patients with ischemic stroke, and monitor cerebral vascular occlusion before and after thrombolysis as well as cerebral vasospasm (VSP) and microembolization signals after aneurysmal subarachnoid hemorrhage (SAH). Moreover, TCD could predict short-term stroke and transient cerebral ischemia in patients with anterior circulation occlusion treated with endovascular therapy and in patients with anterior circulation vascular occlusion. Additionally, TCD not only could monitor blood velocity signals during carotid endarterectomy (CEA) or carotid artery stenting (CAS) but also allowed earlier intervention through early recognition of sickle cell disease (SCD). Presently, TCD is a useful prognostic tool to guide the treatment of CVD. On the one hand, TCD is more commonly applied in clinical research, and on the other hand, TCD has an increasing role in the management of patients. Collectively, we review the principles and clinical application of TCD and propose some new research applications for TCD.

Relationships Between Temporal Leadership, Transactive Memory Systems and Team Innovation Performance.

Background: In recent years, temporal leadership has gradually attracted academic attention. Purpose: This paper discussed the impact of temporal leadership on team innovation performance. Methodology: Through the sample analysis of 385 team members in 98 teams. The measurements of temporal leadership, team innovation performance, transactive memory system, and team reflection were used to measure the relationships between temporal leadership, transactive memory systems and team innovation performance. Findings/Results: It is found that temporal leadership has a positive impact on team innovation performance, which is transmitted through the credibility dimension and coordination dimension of transactive memory systems. Positive team reflection regulates the relationship between temporal leadership and transactive memory systems. Value: This paper reveals the specific impact mechanism of temporal leadership on team innovation performance and provides a new perspective on how to improve team innovation performance in limited time resources.

The effects of adolescent physical activity participation on cell phone dependence: The mediating role of self-control.

BACKGROUND: The rapid development of science and technology and the swift improvement of people's material living standards enabled smartphones to be indispensable of people's daily lives. OBJECTIVE: The purpose of this paper was to examine the influence of self-control in adolescents' participation in physical activity on cell phone dependence. METHODS: The Physical Activity Rating Scale (PARS-3), the Self-Control Scale, and the Cell Phone Dependence Scale were used to measure the influence of self-control in adolescents' participation in physical activity on cell phone dependence among 649 adolescents. RESULTS: The results show: (1) There were significant differences (p < 0.01) in the physical activity levels of adolescents under different gender, birthplace, and education background. (2) Each dimensional variable of physical activity was negatively correlated with the cell phone dependence variable, and positively correlated with each variable of self-control, and the self-control variables were negatively correlated with cell phone dependence. (3) Self-control was partially mediating the effects of physical activity on cell phone dependence, with the mediating effect accounting for 39.68%. CONCLUSIONS: Adolescents' participation in physical exercise activities will improve self-control and ultimately reduce cell phone dependence. Curbing the negative and malignant events of cell phone addiction among adolescents, timely investigation of mobile phone and Internet addiction, pathological formation mechanisms and intervention measures are important measures to reshape the healthy lifestyle of adolescents and have great practical significance for the prosperity and development of families, society, nation and country.

Effects of goal orientation on environment management in technology-based physics learning.

The purpose of the current study is to propose and examine a comprehensive model that uses motivational and self-regulated variables to explain factors affecting environment management in technology-based physics learning among Chinese secondary school students. Data were collected from 726 grade-eight secondary school students in Southeast China, who were learning physics. Structural equation modeling was used to analyze the relationships among students' goal orientations, environment management, and time management. Results suggest that students were more likely to manage their environment if they had learning-oriented goals and if they managed their time, but they were less likely to do so if they had social-oriented goals. Implications for teachers' technology integration in physics class were discussed.