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Objective: Despite the combination of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) being a recognized Chinese medicinal herbal pair that is commonly used in the treatment of ovarian cancer, there is a poor understanding of their pharmacological mechanisms. This study examines the antitumor properties and potential mechanisms of SB-SD on human ovarian cancer A2780 cells through a multi-omics approach, establishing a pharmacological basis for clinical utilization., Methods: A range of mass ratios and reagents were used in the hot reflux extraction of SB-SD. The inhibitory effect of the SB-SD extracts on A2780 cell proliferation was assessed using the cell-counting kit 8 assay. A zebrafish tumor implantation model was used to evaluate the effects of SB-SD extracts on tumor growth and metastasis in vivo. Transcriptomics and proteomics were used to investigate alterations in biological pathways in A2780 cells after treatment with different concentrations of SB-SD extract. Cell cycle, cell apoptosis, intracellular free iron concentration, intracellular reactive oxygen species (ROS) concentration, malondialdehyde (MDA), and mitochondrial membrane potential were measured. Real-time quantitative reverse transcription polymerase chain reaction and Western blotting were utilized to investigate the effects of heme catabolism and ferritinophagy on ferroptosis induced by SB-SD extract in A2780 cells., Results: The 70% ethanol extract of SB-SD (a mass ratio of 4:1) inhibited A2780 cell proliferation significantly with a half maximal inhibitory concentration of 660 μg/mL in a concentration- and time-dependent manner. Moreover, it effectively suppressed tumor growth and metastasis in a zebrafish tumor implantation model. SB-SD extract induced the accumulation of free iron, ROS, MDA, and mitochondrial damage in A2780 cells. The mechanisms might involve the upregulated expression of ferritinophagy-related genes microtubule-associated protein 1 light chain 3, autophagy-related gene 5, and nuclear receptor coactivator 4., Conclusion: SB-SD extract effectively inhibited the development of ovarian cancer both in vitro and in vivo. Its mechanism of action involved inducing ferroptosis by facilitating heme catabolism and ferritinophagy. This herbal pair holds promise as a potential therapeutic option for ovarian cancer treatment and may be utilized in combination with routine treatment to improve the treatment outcomes of ovarian cancer patients. Please cite this article as: Wang Z, Liu M, Li GX, Zhang L, Ding KY, Li SQ, Gao BQ, Chen P, Choe HC, Xia LY, Yang YT, Liu Y, Sui X, Ma JN, Zhang L. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024; Epub ahead of print., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: To observe the effects of electroacupuncture (EA) on sleep quality, sleep structure, and cognitive function in patients with insomnia related to cerebral infarction, and to explore the brain effect mechanism of EA on insomnia related to cerebral infarction., Methods: Thirty-six patients with insomnia related to cerebral infarction were randomly divided into an EA group (18 cases, 1 case was eliminated and 1 case dropped out) and a sham acupuncture group (18 cases, 1 case was eliminated and 2 cases dropped out). Both groups received conventional treatment for cerebral infarction. The EA group received EA at Sishencong (EX-HN 1) with continuous waves at a frequency of 2 Hz, at an intensity tolerable to the patient. The sham acupuncture group received sham acupuncture at non-acupoints with the same EA parameters but electrical stimulation was interrupted after 30 s. Both groups were treated for 20 min each session, once daily, 5 days per week, for a total of 4 weeks. Pittsburgh sleep quality index (PSQI), Montreal cognitive assessment-basic (MoCA-B) scores, and short-term memory (STM) encoding test accuracy and average reaction time were observed before and after treatment in the two groups. Polysomnography (PSG) was used to evaluate sleep structure, and electroencephalogram (EEG) data were collected to observe the standardized power value of the Theta frequency band before and after treatment., Results: Compared with before treatment, PSQI score was decreased and MoCA-B score was increased in the EA group after treatment ( P <0.001); the EA group had lower PSQI score and higher MoCA-B score than those in the sham acupuncture group ( P <0.001, P <0.01). Compared with before treatment, STM encoding test accuracy was increased and average reaction time was shortened in the EA group after treatment ( P <0.01, P <0.001); sleep efficiency (SE) was increased ( P <0.01), total sleep time (TST), REM, and N3 stages were prolonged ( P <0.01, P <0.05), and sleep latency (SL) was shortened ( P <0.01). The standardized power value of the Theta frequency band in EEG channels F3, C3, C4, O1 and O2 was decreased ( P <0.05). After treatment, the EA group had higher STM encoding test accuracy, shorter average reaction time ( P <0.05), higher SE ( P <0.01), longer TST, REM and N3 stages ( P <0.01), and shorter SL ( P <0.01) than those in the sham acupuncture group. There was no statistically significant difference in the standardized power value of the Theta frequency band between the two groups ( P >0.05)., Conclusion: EA could regulate sleep quality and structure in patients with insomnia related to cerebral infarction, and improve cognitive function, possibly related to the reduction of slow-wave activity in EEG.

Background/objectives: Numerical simulation plays an important role in pharmaceutical preparation recently. Mechanistic models, as a type of numerical model, are widely used in the study of pharmaceutical preparations. Mechanistic models are based on a priori knowledge, i.e., laws of physics, chemistry, and biology. However, due to interdisciplinary reasons, pharmacy researchers have greater difficulties in using computer models., Methods: In this paper, we highlight the application scenarios and examples of mechanistic modelling in pharmacy research and provide a reference for drug researchers to get started., Results: By establishing a suitable model and inputting preparation parameters, researchers can analyze the drug preparation process. Therefore, mechanistic models are effective tools to optimize the preparation parameters and predict potential quality problems of the product. With product quality parameters as the ultimate goal, the experiment design is optimized by mechanistic models. This process emphasizes the concept of quality by design., Conclusions: The use of numerical simulation saves experimental cost and time, and speeds up the experimental process. In pharmacy experiments, part of the physical information and the change processes are difficult to obtain, such as the mechanical phenomena during tablet compression and the airflow details in the nasal cavity. Therefore, it is necessary to predict the information and guide the formulation with the help of mechanistic models.

It remains uncertain whether causal structure prediction can improve comprehension in Chinese sentences and whether the position of the headword mediates the prediction effect. We conducted an experiment to explore the effect of causal prediction and headword position in Chinese sentence reading. Participants were asked to read sentences containing causal connectives with their eye movements recorded. In the experiment, we manipulated the causal structure of the sentence and the position of the headword. We found a promoting effect of causal structure on first-pass reading time and a hindering impact on total reading time. However, the effect was not mediated by the headword position. The results show that causal syntactic prediction facilitated early-stage processing and increased the integration cost in the late stage of Chinese sentence processing. These findings also support the constraint-based approach, which suggests an isolation between semantic and syntactic processing., Competing Interests: The authors declare that they have no competing interests., (© 2024 Gao et al.)

Objective: This study examined the effect of context on the prediction of emotional words with varying valences. It investigated the neural mechanisms underlying the processing differences of emotion words with different valences in both predictable and unpredictable contexts. Additionally, it aimed to address the conflicting results regarding the processing time in predictive contexts reported in previous studies., Methods: Participants were instructed to carefully read the text that included the specified emotion words. Event-related potentials elicited by emotional words were measured. To ensure that the participants can read the text carefully, 33% of the texts are followed by comprehension problems. After reading the text, the comprehension questions were answered based on the text content., Results: The study revealed that the N400 amplitude elicited by an unpredictable context was greater than that elicited by a predictable context. Additionally, the N400 amplitude triggered by positive emotion words was larger than that triggered by negative emotion words. However, there was no significant difference in late positive component amplitude observed between contextual prediction and emotional word valence., Conclusion: The present study suggests that predictive processing takes place at an intermediate stage of speech processing, approximately 400 ms after stimulus onset. Furthermore, the presence of a predictive context enhances the processing of emotional information. Notably, brain activity is more pronounced during the processing of positive emotional stimuli compared to negative emotional stimuli. Additionally, the facilitative effect of a predictable context diminishes in the advanced phase of Chinese speech comprehension., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

To study the characteristics of nasal airflow in the presence of nasal cycle by computational fluid dynamics. CT scan data of a healthy Chinese individual was used to construct a three-dimensional model of the nasal cavity to be used as simulation domain. A sinusoidal airflow velocity is set at the nasal cavity entrance to reproduce the breathing pattern of a healthy human. There was a significant difference in the cross-sectional area between the two sides of the nasal cavity. Particularly, the decongested side is characterized by a larger cross-section area, and consequently, by a larger volume with respect to the congested side. The airflow velocity, pressure, and nasal resistance were higher on the congested narrow side. The temperature regulation ability on the congested narrow side was stronger than that on the decongested wider side. During the nasal cycle, there are differences in the nasal cavity function between the congested and decongested sides. Therefore, when evaluating the impact of various factors on nasal cavity function, the nasal cycle should be considered., (© 2024. The Author(s).)

Attention determines what kind of option information is processed during risky choices owing to the limitation of visual attention. This paper reviews research on the relationship between higher-complexity risky decision-making and attention as illustrated by eye-tracking to explain the process of risky decision-making by the effect of attention. We demonstrate this process from three stages: the pre-phase guidance of options on attention, the process of attention being biased, and the impact of attention on final risk preference. We conclude that exogenous information can capture attention directly to salient options, thereby altering evidence accumulation. In particular, for multi-attribute risky decision-making, attentional advantages increase the weight of specific attributes, thus biasing risk preference in different directions. We highlight the significance of understanding how people use available information to weigh risks from an information-processing perspective via process data., (© 2023 The Authors. PsyCh Journal published by Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

This research utilized event-related potential (ERP) recording technology to examine the effect of emotional context on the processing of emotional information in sentences. Three types of emotion-consistent discourse materials (neutral-neutral, positive-positive and negative-negative) were constructed to specifically express neutral, positive and negative emotions, respectively. Each discourse comprised two sentences, with the emotionally significant words embedded at the penultimate position of the second sentence. Participants were asked to read these texts, respond to reading comprehension questions and the ERP amplitude induced by the emotional words was recorded. The results indicated a tripartite interaction in the N400 and Late positive component amplitudes involving emotional context, emotional words and brain hemispheres, observed in both frontal and central brain regions. Notably, there was a significant difference in response to positive words between positive and negative contexts. The findings suggest that emotional context has a substantial effect on the processing of emotional words. Positive words, in comparison to negative ones, are more influenced by emotional context, particularly in the frontal and central regions of the brain., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There has been a significant surge in the global prevalence of diabetes mellitus (DM), which increases the susceptibility of individuals to ovarian cancer (OC). However, the relationship between DM and OC remains largely unexplored. The objective of this study is to provide preliminary insights into the shared molecular regulatory mechanisms and potential biomarkers between DM and OC., Methods: Multiple datasets from the GEO database were utilized for bioinformatics analysis. Single cell datasets from the GEO database were analysed. Subsequently, immune cell infiltration analysis was performed on mRNA expression data. The intersection of these datasets yielded a set of common genes associated with both OC and DM. Using these overlapping genes and Cytoscape, a protein‒protein interaction (PPI) network was constructed, and 10 core targets were selected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were then conducted on these core targets. Additionally, advanced bioinformatics analyses were conducted to construct a TF-mRNA-miRNA coregulatory network based on identified core targets. Furthermore, immunohistochemistry staining (IHC) and real-time quantitative PCR (RT-qPCR) were employed for the validation of the expression and biological functions of core proteins, including HSPAA1, HSPA8, SOD1, and transcription factors SREBF2 and GTAT2, in ovarian tumors., Results: The immune cell infiltration analysis based on mRNA expression data for both DM and OC, as well as analysis using single-cell datasets, reveals significant differences in mononuclear cell levels. By intersecting the single-cell datasets, a total of 119 targets related to mononuclear cells in both OC and DM were identified. PPI network analysis further identified 10 hub genesincludingHSP90AA1, HSPA8, SNRPD2, UBA52, SOD1, RPL13A, RPSA, ITGAM, PPP1CC, and PSMA5, as potential targets of OC and DM. Enrichment analysis indicated that these genes are primarily associated with neutrophil degranulation, GDP-dissociation inhibitor activity, and the IL-17 signaling pathway, suggesting their involvement in the regulation of the tumor microenvironment. Furthermore, the TF-gene and miRNA-gene regulatory networks were validated using NetworkAnalyst. The identified TFs included SREBF2, GATA2, and SRF, while the miRNAs included miR-320a, miR-378a-3p, and miR-26a-5p. Simultaneously, IHC and RT-qPCR reveal differential expression of core targets in ovarian tumors after the onset of diabetes. RT-qPCR further revealed that SREBF2 and GATA2 may influence the expression of core proteins, including HSP90AA1, HSPA8, and SOD1., Conclusion: This study revealed the shared gene interaction network between OC and DM and predicted the TFs and miRNAs associated with core genes in monocytes. Our research findings contribute to identifying potential biological mechanisms underlying the relationship between OC and DM., (© 2023. The Author(s).)

The cisterna magna has been defined as the space between the inferior margin of the cerebellar vermis to the level of the foramen magnum, while an enlarged dorsal subarachnoid space at the occipito-cervical junction extending from the foramen magnum to the upper border of the axis (C2) is still ignored. Recently, the myodural bridge complex is proved to drive the cerebral spinal fluid flowing via this region, we therefore introduce the "occipito-atlantal cistern (OAC)" to better describe the subarachnoid space and provide a detailed rationale. The present study utilized several methods, including MRI, gross anatomical dissection, P45 sheet plastination, and three-dimensional visualization. OAC was observed to be an enlarge subarachnoid space, extending from the foramen magnum to the level of the C2. In the median sagittal plane, OAC was a funnel shape and its anteroposterior dimensions were 15.92 ± 4.20 mm at the level of the C0, 4.49 ± 1.25 mm at the level of the posterior arch of the C1, and 2.88 ± 0.77 mm at the level of the arch of the C2, respectively. In the median sagittal plane, the spino-dural angle of the OAC was calculated to be 35.10 ± 6.91°, and the area of OAC was calculated to be 232.28 ± 71.02 mm 2 . The present study provides OAC is a subarachnoid space independent from the cisterna magna. Because of its distinctive anatomy, as well as theoretical and clinical significance, OAC deserves its own name., (© 2023. The Author(s).)

Objectives: This study seeks to explore the interaction between ignored valence and attended valence in the processing of Chinese emotion words., Methods: The experimental materials utilized in this study consisted of Chinese emotion words. Participants were instructed to observe the words and press a key when presented with target words. Additionally, the electroencephalographic responses of the participants were recorded during the experiment., Results: The results showed that emotional nontarget words elicited greater amplitude of the N170 in the attend-emotion words block compared to the attend-neutral words block. Negative nontarget words produce greater amplitude of the late posterior positivity compared to positive nontarget words. In addition, emotional nontarget words were influenced by both ignored and attended valence, whereby positive nontarget words resulted in larger amplitude of the N170 component in the attend-negative block compared to the attend-neutral block. The modulation pattern for negative nontarget words was evident on the left hemisphere., Conclusion: The findings suggest that emotional nontarget words received greater attentional resources in the attend-emotion words block during the early stages of processing, compared to the attend-neutral word block. Additionally, during the later stages of processing, negative nontarget words were more likely to be processed than positive nontarget words. Overall, these results provide support for the evaluation space model., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Cognitive decision has the basic characteristics of risk avoidance and benefit seeking. To explore the neural response process of cognitive decision making, we asked 32 undergraduates to make a decision on whether to accept a specific treatment option with a certain cure rate and a certain risk rate while recording their electrical brain responses. The results showed that more participants chose the treatment option with a high cure rate and moderate or low risk. Compared with low and high risk, medium risk produced greater N1 and smaller P300. Low risk produced larger LPP than the moderate risk in the left hemisphere. The right prefrontal region appeared to have a smaller LPP for low risk than for high risk. The results suggest that individuals prioritize risk when making cognitive decisions. In addition, in medium-risk conditions, solution integration is more difficult. The effect of benefit size appears at the late stage of cognitive decision making and adjusts the effect of risk. These results support the satisfaction principle of decision making.

Background: PTPN2, a member of the non-receptor protein tyrosine phosphatases family, holds a crucial role in tumorigenesis and cancer immunotherapy. However, most studies on the role of PTPN2 in cancer are limited to specific cancer types. Therefore, this study aimed to investigate the prognostic significance of PTPN2 in human cancers and its function in the tumor microenvironment., Methods: To shed light on this matter, we investigated the expression level, prognostic value, genomic alterations, molecular function, immune function, and immunotherapeutic predictive ability of PTPN2 in human cancers using the TCGA, GTEx, CGGA, GEO, cBioPortal, STRING, TISCH, TIMER2.0, ESTIMATE, and TIDE databases. Furthermore, the CCK-8 assay was utilized to detect the effect of PTPN2 on cell proliferation. Cell immunofluorescence analysis was performed to probe the cellular localization of PTPN2. Western blot was applied to examine the molecular targets downstream of PTPN2. Finally, a Nomogram model was constructed using the TCGA-LGG cohort and evaluated with calibration curves and time-dependent ROCs., Results: PTPN2 was highly expressed in most cancers and was linked to poor prognosis in ACC, GBM, LGG, KICH, and PAAD, while the opposite was true in OV, SKCM, and THYM. PTPN2 knockdown promoted the proliferation of melanoma cells, while significantly inhibiting proliferation in colon cancer and glioblastoma cells. In addition, TC-PTP, encoded by the PTPN2 gene, was primarily localized in the nucleus and cytoplasm and could negatively regulate the JAK/STAT and MEK/ERK pathways. Strikingly, PTPN2 knockdown significantly enhanced the abundance of PD-L1. PTPN2 was abundantly expressed in Mono/Macro cells and positively correlated with multiple immune infiltrating cells, especially CD8 + T cells. Notably, DLBC, LAML, OV, and TGCT patients in the PTPN2-high group responded better to immunotherapy, while the opposite was true in ESCA, KIRC, KIRP, LIHC, and THCA. Finally, the construction of a Nomogram model on LGG exhibited a high prediction accuracy., Conclusion: Immune checkpoint PTPN2 is a powerful biomarker for predicting prognosis and the efficacy of immunotherapy in cancers. Mechanistically, PTPN2 negatively regulates the JAK/STAT and MEK/ERK pathways and the abundance of PD-L1., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Objectives: The aim of this study is to explore the influence of the degree and location of the danger of traffic hazards on the neural reaction process., Methods: 26 automobile drivers were asked to look at the pictures and press buttons on the pictures unrelated to traffic. Electroencephalography responses to traffic-related images were recorded and analyzed., Results: It was found that danger in the central visual region induced a larger amplitude of the N100 component than in the peripheral visual region and the trend of different hazard levels was consistent. The danger in the central visual area also induced a larger amplitude of the P200 component than in the peripheral vision area. In addition, when the danger appeared in the central visual area (0°), the P200 amplitude induced by the low-hazard situation was smaller than that of the high-hazard situation. When the danger appeared in the peripheral visual area (7°), the P200 amplitude induced by the low-hazard situation was larger than that of the high-hazard situation. Finally, the presence of danger evoked a larger amplitude of the P300 component in the peripheral visual area than in the central visual area and the P300 amplitude was larger in the low-hazard situation than in the high-hazard situation., Conclusions: The results suggest that hazards are more easily processed in the central visual area during the early stage of automatic perception. In the later hazard evaluation stage, the hazard in the central visual area and the high-hazard situation were more easily processed., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Esophageal cancer (ESCA) is one of the most common malignant tumors of the digestive system worldwide. As a first-line drug for chemotherapy, cisplatin resistance is the major obstacle in the successful treatment of esophageal cancer. Previous studies largely failed to identify the key genes associated with cisplatin resistance. Hence, the aim of this study was to screen the cisplatin resistance-related genes of esophageal cancer using CRISPR/Cas9 gene-editing technology and Brunello iBar library. Of note, we identified ERCC8 as a novel cisplatin-resistant gene by high-throughput sequencing and cisplatin resistance assays. Based on KEGG and GO analysis, we hypothesized that the mechanism of ERCC8 involvement in cisplatin resistance is through binding to damaged DNA to perform nucleotide excision repair, contributing to the restoration of basic DNA functions and cellular life activities in ESCA. In addition, Cell proliferation and wound healing assay confirmed that ERCC8 had little effect on the proliferation and migration of esophageal cancer cells in vitro. Survival analysis showed that ERCC8 expression was not associated with OS, DSS, or FPI in patients with ESCA. Immuno-infiltration analysis indicated that increased ERCC8 expression is associated with NK cells, macrophages, T helper cells, Th1 cells, and Th2 cells. Collectively, ERCC8 may serve as a new biomarker for predicting cisplatin resistance and have the prospect of becoming an effective target for the clinical treatment of cisplatin resistance in ESCA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Individuals in depressed status respond abnormally to reward stimuli, but the neural processes involved remain unclear. Whether this neural response affects subsequent cognitive processing activities remains to be explored. In the current study, participants, screened as depressed status individuals and healthy individuals by Beck Depression Inventory and Hospital Anxiety Depression Scale, performed both a door task and a cognitive task. Specifically, in each trial, they selected one from two identical doors based on the expectations of rewards and punishments and received the rewarded or punished feedback, and then they performed a cognitive task in which they judged the correctness of a math equation. The neural responses of their choice in the door task were recorded. The results showed that when the two groups received punished feedback, their accuracy was significantly higher than they received rewarded feedback. Compared with the healthy group, the depressed status group spent more time completing cognitive tasks. Analysis of electroencephalography (EEG) data showed that the amplitude of RewP induced by rewarded feedback was larger than that induced by punished feedback, and the amplitude of RewP and fb-P3 induced by the depressed status group was smaller than that of the healthy group. The results of an order analysis showed that the main effects of group variable in fb-P3 and RewP appeared in the second half of the data, and the main effect of feedback type in RewP appeared in the first half of the data. The results showed that the neural response of individuals in depressed status to reward and punishment stimuli was weakened compared with healthy individuals and affected the subsequent cognitive processing to some extent. The effect of feedback appeared in the early stage and gradually decreased. The neural response of individuals in depressed status had a cumulative effect, and the differences appeared in the later stage. The results of this study support the emotional situation insensitive hypothesis, that is, individuals in depressed status are less sensitive to reward and punishment than healthy individuals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Cheng, Li and Sui.)

To explore the influences of traffic-related negative emotions on driving decisions, we induced drivers' three emotions (neutral emotion, traffic-related negative emotion, and traffic-unrelated negative emotion) by videos, then the drivers were shown traffic pictures at different risk levels and made decisions about whether to slow down, while their eye movements were recorded. We found that traffic-related negative emotion influenced driving decisions. Compared with neutral emotion, traffic-related negative emotion led to an increase in the number of decelerations, and the higher the risk, the more the number of decelerations. The visual processing time of the risk area was shorter in the traffic-related negative emotional state than that in the neutral emotional state. The less time drivers spend looking at the risk area, the faster they make their driving decisions. The results suggest that traffic-related negative emotions lead drivers to make more conservative decisions. This study supports the rationality of using traffic accident materials to conduct safety education for drivers. This article also discussed the significance of traffic-related negative emotions to social security., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Chang, Sui and Li.)

The transcription factor Snail1, a key inducer of epithelial-mesenchymal transition (EMT), plays a critical role in tumor metastasis. Its stability is strictly controlled by multiple intracellular signal transduction pathways and the ubiquitin-proteasome system (UPS). Increasing evidence indicates that methylation and acetylation of Snail1 also affects tumor metastasis. More importantly, Snail1 is involved in tumor immunosuppression by inducing chemokines and immunosuppressive cells into the tumor microenvironment (TME). In addition, some immune checkpoints potentiate Snail1 expression, such as programmed death ligand 1 (PD-L1) and T cell immunoglobulin 3 (TIM-3). This mini review highlights the pathways and molecules involved in maintenance of Snail1 level and the significance of Snail1 in tumor immune evasion. Due to the crucial role of EMT in tumor metastasis and tumor immunosuppression, comprehensive understanding of Snail1 function may contribute to the development of novel therapeutics for cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tang, Sui, Weng and Liu.)

The present fMRI study examined the neural basis of processing context-supported or -unsupported interpretations of ambiguous morphemes during Chinese compound word reading in a masked priming lexical decision task. Targets were Chinese bimorphemic words that contained ambiguous morphemes. Prime words contained the same ambiguous morphemes with either the same meanings (context-supported interpretation) or different ones (context-unsupported interpretation). Lexical-level semantic sharing and unrelated control conditions were also included. Compared to the unrelated control condition, the context-supported morphemic meaning was associated with increased activity in the left SFG and bilateral MTG, and this priming effect could be dissociated from that of the lexical-level semantic-related condition. In broader brain regions, including the left SFG, bilateral MTG, left STG, right IOG, and left precuneus, the context-unsupported meaning condition showed decreased activity compared with the unrelated control condition. These findings indicate that both the context-supported and -unsupported meanings evoke significant priming effects, however, they differ from each other with different brain basis, providing new insight into the neural substrates of ambiguous morpheme processing., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study aimed at determining the beneficial effect of Clostridium butyricum (CB) RH2 on ceftriaxone-induced dysbacteriosis. To this purpose, BALB/c mice were exposed to ceftriaxone (400 mg/ml) or not (control) for 7 days, and administered a daily oral gavage of low-, and high-dose CB RH2 (10 8 and 10 10 CFU/ml, respectively) for 2 weeks. CB RH2 altered the diversity of gut microbiota, changed the composition of gut microbiota in phylum and genus level, decreased the F/B ratio, and decreased the pro-inflammatory bacteria ( Deferribacteres , Oscillibacter , Desulfovibrio , Mucispirillum and Parabacteroides ) in ceftriaxone-treated mice. Additionally, CB RH2 improved colonic architecture and intestinal integrity by improving the mucous layer and the tight junction barrier. Furthermore, CB RH2 also mitigated intestinal inflammation through decreasing proinflammatory factors (TNF-α and COX-2) and increasing anti-inflammatory factors (IL-10). CB RH2 had direct effects on the expansion of CD4 + T cells in Peyer's patches (PPs) in vitro , which in turn affected their immune response upon challenge with ceftriaxone. All these data suggested that CB RH2 possessed the ability to modulate the intestinal mucosal and systemic immune system in limiting intestinal alterations to relieve ceftriaxone-induced dysbacteriosis., Competing Interests: Authors HC and LZ were employed by the company Hangzhou Grand Biologic Pharmaceutical INC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Liu, Liu, Sui, Liu, Wei, Liu, Cheng, Ye, Gao, Wang, Lu, Cheng, Zhang, Yuan and Li.)

People often accompany gestures in the process of speaking, but the individual's gesture style is not the same. The present study uses the ambiguity resolution paradigm to explore the influence of two kinds of gesture styles on gesture-verbal comprehension. The study manipulated the gesture styles and meaning types of target words and recorded N400 amplitude. This study found that (1) in the non-grooming condition, compared with the situation where the gesture and semantics are inconsistent, a smaller N400 appears under the consistent condition; (2) in the grooming condition, the grooming gesture will reduce the effect of the iconic gesture on speech understanding. N400 amplitude increased only in the case of matching between dominant meaning gesture and subordinate meaning target word. These results suggest that the communication styles of gestures of different speakers, in the process of speech comprehension, affect how well listeners integrate gestures and language.

Prostaglandin E2 and its cognate EP1-4 receptors play important roles in blood pressure (BP) regulation. Herein, we show that endothelial cell-specific (EC-specific) EP4 gene-knockout mice (EC-EP4-/-) exhibited elevated, while EC-specific EP4-overexpression mice (EC-hEP4OE) displayed reduced, BP levels compared with the control mice under both basal and high-salt diet-fed conditions. The altered BP was completely abolished by treatment with l-NG-nitro-l-arginine methyl ester (l-NAME), a competitive inhibitor of endothelial nitric oxide synthase (eNOS). The mesenteric arteries of the EC-EP4-/- mice showed increased vasoconstrictive response to angiotensin II and reduced vasorelaxant response to acetylcholine, both of which were eliminated by l-NAME. Furthermore, EP4 activation significantly reduced BP levels in hypertensive rats. Mechanistically, EP4 deletion markedly decreased NO contents in blood vessels via reducing eNOS phosphorylation at Ser1177. EP4 enhanced NO production mainly through the AMPK pathway in cultured ECs. Collectively, our findings demonstrate that endothelial EP4 is essential for BP homeostasis.

Glutaric acid is an important organic acid applied widely in different fields. Most previous researches have focused on the production of glutaric acid in various strains using the 5-aminovaleric acid (AMV) or pentenoic acid synthesis pathways. We previously utilized a five-step reversed adipic acid degradation pathway (RADP) in Escherichia coli BL21 (DE3) to construct strain Bgl146. Herein, we found that malonyl-CoA was strictly limited in this strain, and increasing its abundance could improve glutaric acid production. We, therefore, constructed a malonic acid uptake pathway in E. coli using matB (malonic acid synthetase) and matC (malonic acid carrier protein) from Clover rhizobia. The titer of glutaric acid was improved by 2.1-fold and 1.45-fold, respectively, reaching 0.56 g/L and 4.35 g/L in shake flask and batch fermentation following addition of malonic acid. Finally, the highest titer of glutaric acid was 6.3 g/L in fed-batch fermentation at optimized fermentation conditions.

Source camera identification, which aims at identifying the source camera of an image, has attracted a wide range of attention in the field of digital image forensics recently. Many approaches to source camera identification have been proposed by extracting some image features. However, most of these methods only focused on extracting features from the single artifact of the camera left on the captured images and ignored other artifacts that may help improve final accuracy. Therefore, in this paper, we propose a feature-based framework for source camera identification, which first captures various pure camera-specific artifacts through preprocessing and residual calculation, then extracts discriminative features through image transform, and finally reduces the algorithm complexity through feature reduction. Based on the framework, a novel source camera identification method is proposed, which can identify different camera brands, models and individuals with high accuracy. A large number of comparative experiments show that the proposed method outperforms the state-of-the-art methods., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The authenticity of the image is crucial to many cases. The efficient detection of the JPEG compression history of bitmap image could reveal the possibility of tampering on the image. In this paper, we propose a lightweight but reliable JPEG compression detection method based on image information loss. An efficient feature of the decreasing percentage of zero coefficient is proposed to detect the JPEG compression history of an image, due to the increasing JPEG compression quality factor. In our method, estimated original images are first created. Then the given image and its estimated counterpart are compressed to get the JPEG coefficient. After that, the image information loss will be calculated. Through the analysis, the goal of the compression history detection can be achieved. Extensive experimental results have demonstrated that the proposed method outperforms the existing methods.

Source camera identification has been well studied in laboratory environment where the training and test samples are all original images without recompression. However, image compression is quite common in the real world, when the training and test images are double JPEG compressed with different quantization tables, the identification accuracy of existing methods decreases dramati- cally. To address this challenge, we propose a novel iterative algorithm namely joint first and second order statistics matching (JSM) to learn a feature projection that projects the training and test fea- tures into a low dimensional subspace to reduce the shift caused by image recompression. Inspired by transfer learning, JSM aims to learn a new feature representation from original feature space by simultaneously matching the first and second order statistics between training and test features in a principled dimensionality reduction procedure. After the feature projection, the divergence between training and test features caused by recompression is reduced while the discriminative properties are preserved. Extensive experiments on public Dresden Image Database verify that JSM significantly outperforms several state-of-the-art methods on camera model identification of recompressed images.

Candida albicans is the most common fungal microorganism in healthy individuals, as well as the cause of high mortality infections in high-risk hosts such as immunocompromised patients. Antifungal vaccines and monoclonal antibodies useful for active or passive immunizations have recently generated considerable excitement for the treatment of fungal infections. The cell wall proteins of C. albicans, which are crucial for virulence and pathogenicity, are attractive target antigens. Als3p, a member of the C. albicans agglutinin-like sequence (ALS) family, is a hyphal-specific glycophosphatidylinositol cell wall protein that plays a key role in the interaction with host cells. The abundance of Als3p on the hyphal surface makes it an attractive target. For example, the NDV-3 vaccine, targeted at the N-terminus of Als3p, has entered a preparation of Phase 2 clinical trial. The Als3p-specific antibodies include monoclonal antibodies (MAbs) 3-A5, MAb 113, and scFv3. In addition, MAb C7, MAb 3D9.3 and MAb 2G8, which were supposed to be identifying other targets, have also provided good protection by recognizing Als3p. In this review, we summarize the functions of Als3p and highlight the development of the vaccines and the antibodies that are associated, directly or indirectly, with this protein., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Candida albicans is the most common cause of hematogenously disseminated candidiasis, and this disease is particularly prevalent in immunocompromised patients. The mortality of invasive candidiasis remains 40% to 50% even with the proper treatment with current antifungal drugs. Recently, with the better understanding of host-fungus interactions, notable progress has been made in antifungal vaccine research. Most antifungal vaccines exert protection by inducing either (or both) B-cell and T-cell responses. Here we summarize the current available information on C. albicans vaccines, highlight the obstacles that researchers identified, and offer several suggestions.

Candida albicans is one of the most common fungal pathogen in humans due to its high frequency as an opportunistic and pathogenic fungus causing superficial as well as invasive infections in immunocompromised patients. An understanding of gene function in C. albicans is necessary to study the molecular basis of its pathogenesis, virulence and drug resistance. Several manipulation techniques have been used for investigation of gene function in C. albicans, including gene disruption, controlled gene expression, protein tagging, gene reintegration, and overexpression. In this review, the main cassettes containing selectable markers used for gene manipulation in C. albicans are summarized; the advantages and limitations of these cassettes are discussed concerning the influences on the target gene expression and the virulence of the mutant strains.

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent's emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context.

Sabia parviflora Wall. ex Roxb. is a traditional herb widely used by Chinese people, especially by the Buyi ethnic group which resides in Guizhou and Yunnan provinces. According to the Chinese Ethnic Pharmacopeia, the species is commonly used for soothing the liver and for the treatment of icteric hepatitis, hemostasis, and inflammation. However, due to the similar morphological characters of Sabia species and higher market demands, there are many substitutes and adulterants of S. parviflora. In this study, the differential identification of 6 Sabia species and 7 adulterants were investigated through DNA sequence analysis of three candidate DNA barcodes (trnH-psbA, rbcL-α, matK). Based on sequence alignments, we concluded that not only the trnH-psbA spacer sequence can distinguish S. parviflora from other Sabia species, but the matK + rbcL-α sequences also can differentiate it from the substitutes and adulterants. The classification tree of all samples based on rbcL-α sequences indicated that the rbcL region can identify samples into a family/genus level. Our results suggest that the three candidate barcodes can be used for the identification of S. parviflora and to distinguish it from common substitutes or adulterants., (© Georg Thieme Verlag KG Stuttgart · New York.)

Normal cellular functions of hamartin and tuberin, encoded by the TSC1 and TSC2 tumor suppressor genes, are closely related to their direct interactions. However, the regulation of the hamartin-tuberin complex in the context of the physiologic role as tumor suppressor genes has not been documented. Here we show that insulin or insulin growth factor (IGF) 1 stimulates phosphorylation of tuberin, which is inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 but not by the mitogen-activated protein kinase inhibitor PD98059. Expression of constitutively active PI3K or active Akt, including Akt1 and Akt2, induces tuberin phosphorylation. We further demonstrate that Akt/PKB associates with hamartin-tuberin complexes, promoting phosphorylation of tuberin and increased degradation of hamartin-tuberin complexes. The ability to form complexes, however, is not blocked. Akt also inhibits tuberin-mediated degradation of p27(kip1), thereby promoting CDK2 activity and cellular proliferation. Our results indicate that tuberin is a direct physiological substrate of Akt and that phosphorylation of tuberin by PI3K/Akt is a major mechanism controlling hamartin-tuberin function.