Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a common cancer with increasing morbidity and mortality due to changes of social environment. AIM: To evaluate the significance of serum carbohydrate antigen 19-9 (CA19-9) and tumor size changes pre- and post-neoadjuvant therapy (NAT). METHODS: This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital. This study specifically assessed CA19-9 levels and tumor size before and after NAT. RESULTS: A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study. The average age was 65.4 ± 10.6 years and 72 (46.2%) patients were female. Before survival analysis, we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio (CR). The patients were divided into three groups: CR < 0.5, CR > 0.5 and < 1 and CR > 1. With regard to tumor size measured by both computed tomography and magnetic resonance imaging, we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio (TR). The patients were then divided into three groups: TR < 0.5, TR > 0.5 and < 1 and TR > 1. Based on these groups divided according to CR and TR, we performed both overall survival (OS) and disease-free survival (DFS) analyses. Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR (P < 0.05). CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response. Moreover, CR (hazard ratio: 1.721, 95%CI: 1.373-3.762; P = 0.006), and TR (hazard ratio: 1.435, 95%CI: 1.275-4.363; P = 0.014) were identified as independent factors associated with OS. CONCLUSION: This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

Aberrant phenotypes of circulating γδ-T cells may be involved in the onset of systemic lupus erythematosus.

OBJECTIVE: Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE. METHODS: Circulating γδ-T cells and their subsets (Vδ1+ T cells, Vδ2+ T cells and γδ-T-cell subpopulations defined by expression of surface receptors, including NKG2D, NKp30, NKp46 and PD-1), were identified via flow cytometry. Sixty active SLE patients were selected, including 41 new-onset and 19 relapsing cases. One hundred healthy controls (HCs) were enrolled as the control group. Percentages of these cell subsets in SLE patients and HCs and their relationships with disease activity were analysed. Twenty-two of the 41 new-onset SLE patients were assessed before and after treatment. Changes in the frequencies of these cell subsets and their relationships with renal involvement were also analysed. RESULTS: Compared with that in HCs, the percentage of total γδ-T cells among CD3+ T cells in SLE patients was significantly lower. An imbalance in the proportions of Vδ1+ and Vδ2+ T cells among γδ-T cells was observed. The proportion of Vδ1+ T cells among γδ-T cells was significantly greater in SLE patients than in HCs, while the proportion of Vδ2+ T cells was significantly lower. Expression levels of PD-1, NKG2D, NKp30 and NKp46 in Vδ1+ T cells and Vδ2+ T cells from SLE patients were generally significantly increased, except for expression of NKG2D in Vδ2+ T cells. Moreover, Vδ2+ T cells, Vδ1+ T cells and Vδ1+PD-1+ T cells were associated with disease activity, and an increase in Vδ2+ T-cell frequency and a decrease in PD-1 expression by γδ-T cells might be associated with effective treatment. Interestingly, our results indicated that Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation might be associated with renal involvement in SLE. CONCLUSION: A broad range of anomalies in the proportions of γδ-T-cell subsets and γδ-T cells in SLE patients may be involved in the pathogenesis of SLE. There is a strong association between Vδ2+ T cells and their Vδ2+NKp30+ T-cell subpopulation and LN occurrence. Our results indicate that γδ-T cells and their subpopulations might be key players in disease immunopathology and renal involvement in SLE.

Single-cell profile reveals the landscape of cardiac immunity and identifies a cardio-protective Ym-1hi neutrophil in myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) is a major hindrance to the success of cardiac reperfusion therapy. Although increased neutrophil infiltration is a hallmark of MIRI, the subtypes and alterations of neutrophils in this process remain unclear. Here, we performed single-cell sequencing of cardiac CD45+ cells isolated from the murine myocardium subjected to MIRI at six-time points. We identified diverse types of infiltrating immune cells and their dynamic changes during MIRI. Cardiac neutrophils showed the most immediate response and largest changes and featured with functionally heterogeneous subpopulations, including Ccl3hi Neu and Ym-1hi Neu, which were increased at 6 h and 1 d after reperfusion, respectively. Ym-1hi Neu selectively expressed genes with protective effects and was, therefore, identified as a novel specific type of cardiac cell in the injured heart. Further analysis indicated that neutrophils and their subtypes orchestrated subsequent immune responses in the cardiac tissues, especially instructing the response of macrophages. The abundance of Ym-1hi Neu was closely correlated with the therapeutic efficacy of MIRI when neutrophils were specifically targeted by anti-Lymphocyte antigen 6 complex locus G6D (Ly6G) or anti-Intercellular cell adhesion molecule-1 (ICAM-1) neutralizing antibodies. In addition, a neutrophil subtype with the same phenotype as Ym-1hi Neu was detected in clinical samples and correlated with prognosis. Ym-1 inhibition exacerbated myocardial injury, whereas Ym-1 supplementation significantly ameliorated injury in MIRI mice, which was attributed to the tilt of Ym-1 on the polarization of macrophages toward the repair phenotype in myocardial tissue. Overall, our findings reveal the anti-inflammatory phenotype of Ym-1hi Neu and highlight its critical role in myocardial protection during the early stages of MIRI.

Effect of Pleurotus eryngii on the Characteristics of Pork Patties during Freezing and Thawing Cycles.

Temperature fluctuations severely damage the quality, oxidation stability, and structure of pork patties. This study investigated the potential reasons for Pleurotus eryngii (Pe) to protect frozen pork patties from quality degradation caused by temperature fluctuations and promoted the application of a natural ingredient. In this experiment, the pH, the water holding capacity (WHC), the properties of color and texture, the appearance, the degree of protein and lipid oxidation, and the microstructure of patties with different additions of Pe (0%, 0.25%, 0.50%, 1.00%, and 2.00%) were intensified during freezing and thawing (F-T) cycles. The results showed that patties with 0.50% Pe exhibited a distinguishable improvement in the changes of pH, WHC, color, and texture during F-T cycles (p < 0.05). With the times of F-T cycles increasing, 0.50% Pe was able to inhibit lipid oxidation of patties by decreasing the peroxide value (POV) and the thiobarbituric acid reactive substances (TBARS) value to 0.87 and 0.66-fold, respectively, compared to those in the control group. It was also able to suppress the protein oxidation of the patties with a protein sulfhydryl content increasing to 1.13-fold and a carbonyl content decreasing to 0.49-fold compared to the patties in the control group (p < 0.05) after 5 F-T cycles. In addition, the figures of appearance and microstructure of samples indicated that 0.50% Pe effectively restrained the deterioration of structure features from patties after 5 F-T cycles. Thus, the addition of Pe effectively maintained the characteristics of pork patties under F-T cycles.

Developing an evaluation index system for the online learning literacy of physical education teachers in China.

Background: The convenience of online learning helps physical education teachers overcome geographic barriers and promotes safe, accessible, high-quality education. This three-stage study developed an evaluation index system for online learning literacy of physical education (PE) teachers (OLLPET). Methods: Using two rounds of the Delphi method and one round of the Expert ranking method, consult with 15 PE experts from universities, primary and secondary schools, and teaching-research staff to draw up, revise, and finalize an evaluation index system for OLLPET. Results: Our OLLPET evaluation index system includes three first-level indicators, seven second-level indicators and 30 third-level indicators. The first-level indicators includes online learning values (OLV), online learning essential character (OLEC), and online learning key competencies (OLKC)-with equal weighting given to OLV (0.367) and OLKC (0.367) and slightly less given to OLEC (0.267). Conclusion: The OLLPET evaluation index system is a theoretical yet practical tool that governments, schools, and teachers can use to evaluate PE teachers' online learning literacy to improve their learning capacity in a targeted manner.

Activation of ETAR and ETBR in myocardial tissue characterizes heart failure induced by experimental autoimmune myocarditis.

BACKGROUND: Endothelial dysfunction is characterized by an imbalance between endothelium-derived vasodilatory and vasoconstrictive effects and may play an important role in the development of heart failure. An increasing number of studies have shown that endothelial-derived NO-mediated vasodilation is attenuated in heart failure patients. However, the role of endothelin-1 (ET-1) in heart failure remains controversial due to its different receptors including ET-1 receptor type A (ETAR) and ET-1 receptor type B (ETBR). The aim of this study was to determine whether ET-1 and its receptors are activated and to explore the role of ETAR and ETBR in heart failure induced by myocarditis. METHODS: We constructed an animal model of experimental autoimmune myocarditis (EAM) with porcine cardiac myosin. Twenty rats were randomized to the control group (3 weeks, n = 5), the extended control group (8 weeks, n = 5), the EAM group (3 weeks, n = 5), the extended EAM group (8 weeks, n = 5). HE staining was used to detect myocardial inflammatory infiltration and the myocarditis score, Masson's trichrome staining was used to assess myocardial fibrosis, echocardiography was used to evaluate cardiac function, ELISA was used to detect serum NT-proBNP and ET-1 concentrations, and immunohistochemistry and western blotting were used to detect ETAR and ETBR expression in myocardial tissue of EAM-induced heart failure. Subsequently, a model of myocardial inflammatory injury in vitro was constructed to explore the role of ETAR and ETBR in EAM-induced heart failure. RESULTS: EAM rats tended to reach peak inflammation after 3 weeks of immunization and developed stable chronic heart failure at 8 weeks after immunization. LVEDd and LVEDs were significantly increased in the EAM group compared to the control group at 3 weeks and 8 weeks after immunization while EF and FS were significantly reduced. Serum NT-proBNP concentrations in EAM (both 3 weeks and 8 weeks) were elevated. Therefore, EAM can induce acute and chronic heart failure due to myocardial inflammatory injury. Serum ET-1 concentration and myocardial ETAR and ETBR protein were significantly increased in EAM-induced heart failure in vivo. Consistent with the results of the experiments in vivo, ETAR and ETBR protein expression levels were significantly increased in the myocardial inflammatory injury model in vitro. Moreover, ETAR gene silencing inhibited inflammatory cytokine TNF-α and IL-1ß levels, while ETBR gene silencing improved TNF-α and IL-1ß levels. CONCLUSIONS: ET-1, ETAR, and ETBR were activated in both EAM-induced acute heart failure and chronic heart failure. ETAR may positively regulate EAM-induced heart failure by promoting myocardial inflammatory injury, whereas ETBR negatively regulates EAM-induced heart failure by alleviating myocardial inflammatory injury.

Manganese-induced neurological pyroptosis: Unveiling the mechanism through the ROS activaed Caspase-3/GSDME signaling pathway.

Manganese (Mn) is an essential micronutrient in maintaining homeostasis in the human body, while excessive Mn exposure can lead to neurological disorders. To investigate whether there is an association between elevated ROS and pyroptosis caused by Mn exposure using both in vitro and in vivo models. We exposed BV2 and N2a, which represent microglial cells and Neuroblastoma cells in the brain, respectively, to different concentrations of Mn for 24 h. Following Mn exposure, we assessed cell morphology, levels of lactate dehydrogenase, and cellular ROS levels. C57BL/6 male mice were exposed to 0-100 mg/kg MnCl2·4H2O for 12 weeks through gavage. The expression level of pyroptosis proteins including caspase3 and GSDME in the hippocampus was examined. We found that Mn exposure resulted in elevated levels of cellular ROS and protein expression of Caspase3 and GSDME in both N2a and BV2 cells. The pyroptosis levels were blunted by either inhibiting Caspase3 expression or ROS production. In the in vivo model, protein levels of Caspase3 and GSDME also increased dependent of Mn concentrations. These findings suggested that neuronal pyroptosis induced by Mn exposure may occur through the ROS-stimulated Caspase3-GSDME pathway. Moreover, utilizing inhibitors targeting Caspase3 or ROS may provide protection against Mn-induced toxicity.

ET-1 receptor type B (ETBR) overexpression associated with ICAM-1 downregulation leads to inflammatory attenuation in experimental autoimmune myocarditis.

Background: An experimental autoimmune myocarditis rat model was established by subcutaneous injection of porcine myocardial myosin (PCM). The effect of ET-1 receptor type B (ETBR) overexpression on autoimmune myocarditis was observed via tail vein injection of ETBR overexpression lentivirus in rats. We further investigated the mechanisms involved in the regulation of autoimmune myocarditis by ETBR overexpression. Methods: Six rats were randomly selected from 24 male Lewis rats as the NC group, and the remaining 18 rats were injected with PCM on Day 0 and Day 7, to establish the experimental autoimmune myocarditis (EAM) rat model. The 18 rats initially immunized were randomly divided into three groups: the EAM group, ETBR-oe group, and GFP group. On Day 21 after the initial immunization of rats, cardiac echocardiography and serum brain natriuretic peptide (BNP) analysis were performed to evaluate cardiac function, myocardial tissue HE staining was performed to assess myocardial tissue inflammatory infiltration and the myocarditis score, and mRNA expression of IFN-γ, IL-12, and IL-17 was detected by qRT-PCR. Subsequently, immunohistochemical analysis was performed to detect the localization and expression of the ETBR and ICAM-1 proteins, and the expression of ETBR and ICAM-1 was verified by qRT-PCR and western blotting methods. Results: On Day 21 after initial immunization, left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), and serum BNP concentrations increased in the hearts of rats in the EAM group compared with the NC group (P < 0.01), and ejection fraction (EF) and fractional shortening (FS) decreased compared with those of the normal control (NC) group (P < 0.01). LVEDd, LVEDs, and serum BNP concentrations decreased in the ETBR-oe group compared with the EAM group, while EF and FS increased significantly (P < 0.01). HE staining showed that a large number of inflammatory cell infiltrates, mainly lymphocytes, were observed in the EAM group, and the myocarditis score was significantly higher than that of the NC group (P < 0.01). Compared with that of the EAM group, myocardial tissue inflammatory cell infiltration was significantly reduced in the ETBR-oe group, and the myocarditis scores were significantly lower (P < 0.01). The mRNAs of the inflammatory factors IFN-γ, IL-12 and IL-17 in myocardial tissue of rats in the EAM group exhibited elevated levels compared with those of the NC group (P < 0.01) while the mRNAs of IFN-γ, IL-12 and IL-17 were significantly decreased in the ETBR-oe group compared with the EAM group (P < 0.01). Immunohistochemistry showed that the staining depth of ETBR protein in myocardial tissue was greater in the EAM group than in the NC group, and significantly greater in the ETBR-oe group than in the EAM group, while the staining depth of ICAM-1 was significantly greater in the EAM group than in the NC group, and significantly lower in the ETBR-oe group than in the EAM group. The ICAM-1 expression level was significantly higher in the EAM group than in the NC group (P < 0.01), and was significantly lower in the ETBR-oe groupthan in the EAM group (P < 0.01).

Mechanistic Insights into the Roles of the IL-17/IL-17R Families in Pancreatic Cancer.

The members of the cytokine interleukin 17 (IL-17) family, along with their receptors (IL-17R), are vital players in a range of inflammatory diseases and cancer. Although generally regarded as proinflammatory, the effects they exhibit on cancer progression are a double-edged sword, with both antitumor and protumor activities being discovered. There is growing evidence that the IL-17 signaling pathways have significant impacts on the tumor microenvironment (TME), immune response, and inflammation in various types of cancer, including pancreatic cancer. However, the detailed mechanistic functions of the IL-17/IL-17R families in pancreatic cancer were rarely systematically elucidated. This review considers the role of the IL-17/IL-17R families in inflammation and tumor immunity and elaborates on the mechanistic functions and correlations of these members with pathogenesis, progression, and chemoresistance in pancreatic cancer. By summarizing the advanced findings on the role of IL-17/IL17R family members and IL-17 signaling pathways at the molecular level, cellular level, and disease level in pancreatic cancer, this review provides an in-depth discussion on the potential of IL-17/IL-17R as prognostic markers and therapeutic targets in pancreatic cancer.

Pressure-modulated lattice structural evolution in TiS2.

Titanium disulfide (TiS2) has drawn considerable attention in materials, physics, and chemistry thanks to its potential applications in batteries, supercapatteries and thermoelectric devices. However, the simplified and controlled synthesis of high-quality TiS2 remains a great challenge. In this study, a straightforward widely accessible approach to the one-step chemical vapor transport (CVT) process is presented. Meanwhile, combining high-pressure (HP) Raman spectroscopy measurements and first-principles calculations, the pressure-induced phase transition of TiS2 from P3̄m1 phase (phase I) to C2/m phase (phase II) at 16.0 GPa and then to P6̄2m phase (phase III) at 32.4 GPa was disclosed. The discovery of HP being within the Weyl semi-metallic phase represents a significant advancement towards understanding the electronic topological states, discovering new physical phenomena, developing new electronic devices, and gaining insight into the properties of elementary particles.

Security Analysis of Distributed Consensus Filtering Under Replay Attacks.

This work studies the security of consensus-based distributed filtering under the replay attack, which can freely select a part of sensors and modify their measurements into previously recorded ones. We analyze the performance degradation of distributed estimation caused by the replay attack, and utilize the Kullback-Leibler (K-L) divergence to quantify the attack stealthiness. Specifically, for a stable system, we prove that under any replay attack, the estimation error is not only bounded, but also can re-enter the steady state. In that case, we prove that the replay attack is ϵ -stealthy, where ϵ can be calculated based on two Lyapunov equations. On the other hand, for an unstable system, we prove that the trace of estimation error covariance is lower bounded by an exponential function, which indicates that the estimation error may diverge due to the attack. In view of this, we provide a sufficient condition to ensure that any replay attack is detectable. Furthermore, we analyze the case that the adversary starts to attack only if the current measurement is close to a previously recorded one. Finally, we verify the theoretical results via several numerical simulations.

Development and validation of the social media perception scale for preservice physical education teachers.

Background: Social media has become a mainstay of preservice physical education teachers' professional development. However, previous studies have been dominated by qualitative research, and there is still a lack of quantitative research based on samples from eastern countries. The objective of this study is to develop and validate of the Social Media Perception Scale for Preservice Physical Education teachers (SMPS-PPE). Method: Items of questionnaire created from 70 concepts of the perception model described in our previous study. Questionnaire survey was used to collect quantitative data from a sample of 977 preservice physical education teachers through surveys. We analyzed the data using SPSS 26.0 and AMOS 24.0, conducting item analysis, exploratory factor analysis and confirmatory factor analysis to examine the data. Results: SMPS-PPE consists of 26 items grouped into three factors: value perception, risk perception, and overall perception. Our findings indicate that SMPS-PPE has acceptable content validity, internal structure validity, and internal consistency. Conclusion: SMPS-PPE is a reliable and valid measurement to evaluate social media perception among preservice physical education teachers. Future studies should include larger and more diverse teacher samples to enhance generalizability. The SMPS-PPE should also be modified to better cater to the specific requirements of school teachers and university-based teacher educators in the field of physical education.

An improved algorithm for inferring mutational parameters from bar-seq evolution experiments.

BACKGROUND: Genetic barcoding provides a high-throughput way to simultaneously track the frequencies of large numbers of competing and evolving microbial lineages. However making inferences about the nature of the evolution that is taking place remains a difficult task. RESULTS: Here we describe an algorithm for the inference of fitness effects and establishment times of beneficial mutations from barcode sequencing data, which builds upon a Bayesian inference method by enforcing self-consistency between the population mean fitness and the individual effects of mutations within lineages. By testing our inference method on a simulation of 40,000 barcoded lineages evolving in serial batch culture, we find that this new method outperforms its predecessor, identifying more adaptive mutations and more accurately inferring their mutational parameters. CONCLUSION: Our new algorithm is particularly suited to inference of mutational parameters when read depth is low. We have made Python code for our serial dilution evolution simulations, as well as both the old and new inference methods, available on GitHub ( https://github.com/FangfeiLi05/FitMut2 ), in the hope that it can find broader use by the microbial evolution community.

Timosaponin AIII promotes non-small-cell lung cancer ferroptosis through targeting and facilitating HSP90 mediated GPX4 ubiquitination and degradation.

Timosaponin AIII (Tim-AIII), a steroid saponin, exhibits strong anticancer activity in a variety of cancers, especially breast cancer and liver cancer. However, the underlying mechanism of the effects of Tim-AIII-mediated anti-lung cancer effects remain obscure. In this study, we showed that Tim-AIII suppressed cell proliferation and migration, induced G2/M phase arrest and ultimately triggered cell death of non-small cell lung cancer (NSCLC) cell lines accompanied by the release of reactive oxygen species (ROS) and iron accumulation, malondialdehyde (MDA) production, and glutathione (GSH) depletion. Interestingly, we found that Tim-AIII-mediated cell death was reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Meanwhile, the heat shock protein 90 (HSP90) was predicted and verified as the direct binding target of Tim-AIII by SwissTargetPrediction (STP) and surface plasmon resonance (SPR) assay. Further study showed that Tim-AIII promoted HSP90 expression and Tim-AIII induced cell death was blocked by the HSP90 inhibitor tanespimycin, indicating that HSP90 was the main target of Tim-AIII to further trigger intracellular events. Mechanical analysis revealed that the Tim-AIII-HSP90 complex further targeted and degraded glutathione peroxidase 4 (GPX4), and promoted the ubiquitination of GPX4, as shown by an immunoprecipitation, degradation and in vitro ubiquitination assay. In addition, Tim-AIII inhibited cell proliferation, induced cell death, led to ROS and iron accumulation, MDA production, GSH depletion, as well as GPX4 ubiquitination and degradation, were markedly abrogated when HSP90 was knockdown by HSP90-shRNA transfection. Importantly, Tim-AIII also showed a strong capacity of preventing tumor growth by promoting ferroptosis in a subcutaneous xenograft tumor model, whether C57BL/6J or BALB/c-nu/nu nude mice. Together, HSP90 was identified as a new target of Tim-AIII. Tim-AIII, by binding and forming a complex with HSP90, further targeted and degraded GPX4, ultimately induced ferroptosis in NSCLC. These findings provided solid evidence that Tim-AIII can serve as a potential candidate for NSCLC treatment.

Dynamic evolution of brain structural patterns in liver transplantation recipients: a longitudinal study based on 3D convolutional neuronal network model.

OBJECTIVES: To evaluate the dynamic evolution process of overall brain health in liver transplantation (LT) recipients, we employed a deep learning-based neuroanatomic biomarker to measure longitudinal changes of brain structural patterns before and 1, 3, and 6 months after surgery. METHODS: Because of the ability to capture patterns across all voxels from a brain scan, the brain age prediction method was adopted. We constructed a 3D-CNN model through T1-weighted MRI of 3609 healthy individuals from 8 public datasets and further applied it to a local dataset of 60 LT recipients and 134 controls. The predicted age difference (PAD) was calculated to estimate brain changes before and after LT, and the network occlusion sensitivity analysis was used to determine the importance of each network in age prediction. RESULTS: The PAD of patients with cirrhosis increased markedly at baseline (+ 5.74 years) and continued to increase within one month after LT (+ 9.18 years). After that, the brain age began to decrease gradually, but it was still higher than the chronological age. The PAD values of the OHE subgroup were higher than those of the no-OHE, and the discrepancy was more obvious at 1-month post-LT. High-level cognition-related networks were more important in predicting the brain age of patients with cirrhosis at baseline, while the importance of primary sensory networks increased temporarily within 6-month post-LT. CONCLUSIONS: The brain structural patterns of LT recipients showed inverted U-shaped dynamic change in the early stage after transplantation, and the change in primary sensory networks may be the main contributor. KEY POINTS: • The recipients' brain structural pattern showed an inverted U-shaped dynamic change after LT. • The patients' brain aging aggravated within 1 month after surgery, and the subset of patients with a history of OHE was particularly affected. • The change of primary sensory networks is the main contributor to the change in brain structural patterns.

The toxic natural product tutin causes epileptic seizures in mice by activating calcineurin.

Tutin, an established toxic natural product that causes epilepsy in rodents, is often used as a tool to develop animal model of acute epileptic seizures. However, the molecular target and toxic mechanism of tutin were unclear. In this study, for the first time, we conducted experiments to clarify the targets in tutin-induced epilepsy using thermal proteome profiling. Our studies showed that calcineurin (CN) was a target of tutin, and that tutin activated CN, leading to seizures. Binding site studies further established that tutin bound within the active site of CN catalytic subunit. CN inhibitor and calcineurin A (CNA) knockdown experiments in vivo proved that tutin induced epilepsy by activating CN, and produced obvious nerve damage. Together, these findings revealed that tutin caused epileptic seizures by activating CN. Moreover, further mechanism studies found that N-methyl-D-aspartate (NMDA) receptors, gamma-aminobutyric acid (GABA) receptors and voltage- and Ca2+- activated K+ (BK) channels might be involved in related signaling pathways. Our study fully explains the convulsive mechanism of tutin, which provides new ideas for epilepsy treatment and drug development.

Fit-Seq2.0: An Improved Software for High-Throughput Fitness Measurements Using Pooled Competition Assays.

The fitness of a genotype is defined as its lifetime reproductive success, with fitness itself being a composite trait likely dependent on many underlying phenotypes. Measuring fitness is important for understanding how alteration of different cellular components affects a cell's ability to reproduce. Here, we describe an improved approach, implemented in Python, for estimating fitness in high throughput via pooled competition assays.

Ultrafast dynamics under high-pressure.

High-pressure is a mechanical method to regulate the structure and internal interaction of materials. Therefore, observation of properties' change can be realized in a relatively pure environment. Furthermore, high-pressure affects the delocalization of wavefunction among materials' atoms and thus their dynamics process. Dynamics results are essential data for understanding the physical and chemical characteristics, which is valuable for materials application and development. Ultrafast spectroscopy is a powerful tool to investigate dynamics process and becoming a necessary characterization method for materials investigation. The combination of high-pressure with ultrafast spectroscopy in the nanocosecond∼femtosecond scale enables us to investigate the influence of the enhanced interaction between particles on the physical and chemical properties of materials, such as energy transfer, charge transfer, Auger recombination, etc. Base on this point of view, this review summarizes recent progress in the ultrafast dynamics under high-pressure for various materials, in which new phenomena and new mechanisms are observed. In this review, we describe in detail the principles ofin situhigh pressure ultrafast dynamics probing technology and its field of application. On this basis, the progress of the study of dynamic processes under high-pressure in different material systems is summarized. An outlook onin situhigh-pressure ultrafast dynamics research is also provided.

The Risk Factors and Outcomes for Radiological Abnormalities in Early Convalescence of COVID-19 Patients Caused by the SARS-CoV-2 Omicron Variant: A Retrospective, Multicenter Follow-up Study.

BACKGROUND: The emergence of the severe acute respiratory syndrome coronavirus 2 omicron variant has been triggering the new wave of coronavirus disease 2019 (COVID-19) globally. However, the risk factors and outcomes for radiological abnormalities in the early convalescent stage (1 month after diagnosis) of omicron infected patients are still unknown. METHODS: Patients were retrospectively enrolled if they were admitted to the hospital due to COVID-19. The chest computed tomography (CT) images and clinical data obtained at baseline (at the time of the first CT image that showed abnormalities after diagnosis) and 1 month after diagnosis were longitudinally analyzed. Uni-/multi-variable logistic regression tests were performed to explore independent risk factors for radiological abnormalities at baseline and residual pulmonary abnormalities after 1 month. RESULTS: We assessed 316 COVID-19 patients, including 47% with radiological abnormalities at baseline and 23% with residual pulmonary abnormalities at 1-month follow-up. In a multivariate regression analysis, age ≥ 50 years, body mass index ≥ 23.87, days after vaccination ≥ 81 days, lymphocyte count ≤ 1.21 × 10-9/L, interleukin-6 (IL-6) ≥ 10.05 pg/mL and IgG ≤ 14.140 S/CO were independent risk factors for CT abnormalities at baseline. The age ≥ 47 years, presence of interlobular septal thickening and IL-6 ≥ 5.85 pg/mL were the independent risk factors for residual pulmonary abnormalities at 1-month follow-up. For residual abnormalities group, the patients with less consolidations and more parenchymal bands at baseline could progress on CT score after 1 month. There were no significant changes in the number of involved lung lobes and total CT score during the early convalescent stage. CONCLUSION: The higher IL-6 level was a common independent risk factor for CT abnormalities at baseline and residual pulmonary abnormalities at 1-month follow-up. There were no obvious radiographic changes during the early convalescent stage in patients with residual pulmonary abnormalities.

Multi-Sensor Fusion Boolean Bayesian Filtering for Stochastic Boolean Networks.

Stochastic Boolean networks (SBNs) take process noise into account, so it is better to fit the actual situation and has a wider application background than Boolean networks (BNs). However, the presence of noise influences us to estimate the real state of the system. To minimize the inaccuracies caused by the presence of noise, an optimal state estimation problem is studied in this article. The multi-sensor fusion Boolean Bayesian filtering is proposed and a recursive algorithm is provided to calculate the prior and posterior belief of system state by fusing multi-sensor measurements based on the algebraic form of the SBN and Bayesian law. Then, the optimal state estimator is obtained, which minimizes the mean-square estimation error. Finally, a simulation example is carried out to demonstrate the performance of the proposed methodology. It has been shown through the simulation experiment that it increases the confidence level of the state estimation and improves the estimation performance using multi-sensor fusion compared with using single sensor.