Influence of presentation duration on filtering of irrelevant stimuli in visual working memory.

In environments teeming with distractions, the ability to selectively focus on relevant information is crucial for advanced cognitive processing. Existing research using event-related potential (ERP) technology has shown active suppression of irrelevant stimuli during the consolidation phase of visual working memory (VWM). In previous studies, participants have always been given sufficient time to consolidate VWM, while suppressing distracting information. However, it remains unclear whether the suppression of irrelevant distractors requires continuous effort throughout their presence or whether this suppression is only necessary after the consolidation of task-relevant information. To address this question, our study examines whether distractor suppression is necessary in scenarios where consolidation time is limited. This research investigates the effect of varying presentation durations on the filtering of distractors in VWM. We tasked participants with memorizing two color stimuli and ignoring four distractors, presented for either 50 ms or 200 ms. Using ERP technology, we discovered that the distractor-induced distractor positivity (PD) amplitude is larger during longer presentation durations compared to shorter ones. These findings underscore the significant impact of presentation duration on the efficacy of distractor suppression in VWM, as prolonged exposure results in a stronger suppression effect on distractors. This study sheds light on the temporal dynamics of attention and memory, emphasizing the critical role of stimulus timing in cognitive tasks. These findings provide valuable insights into the mechanisms underlying VWM and have significant implications for models of attention and memory.

Perceptual encoding benefit of visual memorability on visual memory formation.

Human observers often exhibit remarkable consistency in remembering specific visual details, such as certain face images. This phenomenon is commonly attributed to visual memorability, a collection of stimulus attributes that enhance the long-term retention of visual information. However, the exact contributions of visual memorability to visual memory formation remain elusive as these effects could emerge anywhere from early perceptual encoding to post-perceptual memory consolidation processes. To clarify this, we tested three key predictions from the hypothesis that visual memorability facilitates early perceptual encoding that supports the formation of visual short-term memory (VSTM) and the retention of visual long-term memory (VLTM). First, we examined whether memorability benefits in VSTM encoding manifest early, even within the constraints of a brief stimulus presentation (100-200 ms; Experiment 1). We achieved this by manipulating stimulus presentation duration in a VSTM change detection task using face images with high- or low-memorability while ensuring they were equally familiar to the participants. Second, we assessed whether this early memorability benefit increases the likelihood of VSTM retention, even with post-stimulus masking designed to interrupt post-perceptual VSTM consolidation processes (Experiment 2). Last, we investigated the durability of memorability benefits by manipulating memory retention intervals from seconds to 24 h (Experiment 3). Across experiments, our data suggest that visual memorability has an early impact on VSTM formation, persisting across variable retention intervals and predicting subsequent VLTM overnight. Combined, these findings highlight that visual memorability enhances visual memory within 100-200 ms following stimulus onset, resulting in robust memory traces resistant to post-perceptual interruption and long-term forgetting.

A negative emotional state impairs individuals' ability to filter distractors from working memory: an ERP study.

Capacity-limited visual working memory (VWM) requires that individuals have sufficient memory space and the ability to filter distractors. Negative emotional states are known to impact VWM storage, yet their influence on distractor filtering within VWM remains underexplored. We conducted direct neural measurement of participants (n = 56) who conducted a lateralized change detection task with distractors, while manipulating the emotional state by presenting neutral or negative images before each trial. We found a detrimental effect of distractors on memory accuracy under both neutral and negative emotional states. Using the event-related potential (ERP) component, contralateral delay activity (CDA; sensitive to VWM load), to observe the VWM load in each condition, we found that in the neutral state, the participants showed significantly higher late CDA amplitudes when remembering 4 targets compared with 2 targets and 2 targets with 2 distractors but no significant difference when remembering 2 targets compared with 2 targets with 2 distractors. In the negative state, no significant CDA amplitude differences were evident when remembering 4 targets and 2 targets, but CDA was significantly higher when remembering 2 targets with 2 distractors compared with 2 targets. These results suggest that the maximum number of items participants could store in VWM was lower under negative emotional states than under neutral emotional states. Importantly, the participants could filter out distractors when in a neutral emotional state but not in a negative emotional state, indicating that negative emotional states impair their ability to filter out distractors in VWM.

Sustained attention required for effective dimension-based retro-cue benefit in visual working memory.

In visual working memory (VWM) tasks, participants' performances can be improved through the use of dimension-based retro-cues, which direct internal attention to prioritize a particular dimension (e.g., color or orientation) of VWM representations even after the stimuli disappear. This phenomenon is known as the dimension-based retro-cue benefit (RCB). The present study investigates whether sustained attention is required for the dimension-based RCB by inserting interference or interruption between the retro-cue and the test array to distract attention. We tested the effects of perceptual interference or cognitive interruption on dimension-based RCB when the interference (Experiments 1 and 2 with masks) or interruption (Experiments 3 and 4 with an odd-even task) occurred concurrently with the stages for the maintenance of prioritized information (long cue-and-interference/interruption interstimulus interval, e.g., Experiments 1 and 3) or the deployment of attention (short cue-and-interference/interruption interstimulus interval, e.g., Experiments 2 and 4). Our results demonstrate that perceptual interference or cognitive interruption attenuates the dimension-based RCB. These findings suggest that sustained attention is necessary for the effective prioritization of a specific dimension of VWM representations.

Efficacy and Prognostic Factors of Immune Checkpoint Inhibitors in the Treatment of Advanced Non-small Cell Lung Cancer.

OBJECTIVE: To discuss the efficacy and potential prognostic factors of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A retrospective study was conducted to analyze the medical history of patients (n=111) confirmed with advanced NSCLC in the Affiliated Hospital of Putian University from 2018 to 2020. All enrolled patients with adenocarcinoma (n=69), squamous cell carcinoma (n=28), and other types of lung cancer (n=14) were treated with the programmed death-ligand 1 (PD-1) inhibitors. They were divided into groups of PD-1 inhibitors, PD-1 inhibitors in combination with chemotherapy, and PD-1 inhibitors in combination with chemotherapy and angiogenesis inhibitors according to the treatment regimen. General clinical data of all patients were collected, and the Kaplan-Meier analysis was applied to estimate progression-free survival (PFS) and overall survival (OS). In addition, univariate and multivariate Cox regression analyses were performed to analyze prognostic factors associated with PFS and OS after treatment. RESULTS: Of 111 patients with advanced NSCLC treated with ICIs, 6 were fully responsive, 33 were partially responsive, 55 were stable, and 17 were progressive. There was no significant difference in objective response rate between the 3 groups. In the subgroup analysis according to the lines of therapy, the objective response rate of patients receiving first-line treatment was 46.7%, which was significantly higher than that of other line treatment groups ( P =0.014). The results of multivariate Cox regression analysis indicated that the history of hormone use (HR=1.593; P =0.033), second-line or further lines of therapy (HR=2.871; P <0.001), and high neutrophil/lymphocyte ratio (NLR; HR=1.498; P =0.045) were independent risk factors for PFS after immunotherapy for advanced NSCLC. And the history of hormone use (HR=1.518; P =0.015) and high NLR (HR=3.053; P =0.001) were as well the independent risk factors for OS after immunotherapy for advanced NSCLC. CONCLUSION: ICIs therapy clearly had a greater survival benefit in patients who received first-line therapy, had no history of hormone use, and showed low NLR after initial treatment. ICIs can be an effective treatment for advanced NSCLC.

Self-detection remains a primary means of breast cancer detection in Beijing, China.

Background: Breast cancer in China is usually identified at a later-stage compared to developed countries, and efforts have been made to improve early detection over the past years. This cross-sectional study aimed to determine the current situation of breast cancer detection and screening in a cohort of Chinese breast cancer patients. Methods: Three hundred and ten consecutive female breast cancer patients newly diagnosed and treated in Beijing Tsinghua Changgung Hospital between 2015 and 2021 were recruited. Clinicopathological data were retrieved from the patient's medical records and every individual completed surveys assessing demographics, mode of detection, screening behavior and barriers to screening. Results: Among the 310 patients, 72.6% had self-detected diseases (mostly through identification of a breast lump), 24.5% were ultrasound screening-detected, 0.3% were mammographic screening-detected and others were identified through clinical breast examination (CBE) (1.0%) or chest computed tomography (CT)/magnetic resonance imaging (MRI) (1.6%). Detection by screening was associated with earlier stages of breast cancer compared to self-detection, yet, 32.2% of self-detected diseases were at stage 0-I. A total of 166 (53.5%) patients had a screening history, with ultrasonography being mostly used and provided by employers. Leading self-perceived barrier to breast cancer screening was lack of awareness, followed by lack of access. And screening participation was associated with a younger age, higher education, being currently working, residence in urban area, and a high family income. Conclusions: Self-detection still remains a major way of breast cancer detection in Beijing, but it is not necessarily associated with a late-stage disease. The suboptimal screening rate with disparity in screening behavior can be mostly attributed to lack of awareness of the public and insufficient screening providers.

Encoding specificity instead of online integration of real-world spatial regularities for objects in working memory.

Most objects show high degrees of spatial regularity (e.g. beach umbrellas appear above, not under, beach chairs). The spatial regularities of real-world objects benefit visual working memory (VWM), but the mechanisms behind this spatial regularity effect remain unclear. The "encoding specificity" hypothesis suggests that spatial regularity will enhance the visual encoding process but will not facilitate the integration of information online during VWM maintenance. The "perception-alike" hypothesis suggests that spatial regularity will function in both visual encoding and online integration during VWM maintenance. We investigated whether VWM integrates sequentially presented real-world objects by focusing on the existence of the spatial regularity effect. Throughout five experiments, we manipulated the presentation (simultaneous vs. sequential) and regularity (with vs. without regularity) of memory arrays among pairs of real-world objects. The spatial regularity of memory objects presented simultaneously, but not sequentially, improved VWM performance. We also examined whether memory load, verbal suppression and masking, and memory array duration hindered the spatial regularity effect in sequential presentation. We found a stable absence of the spatial regularity effect, suggesting that the participants were unable to integrate real-world objects based on spatial regularities online. Our results support the encoding specificity hypothesis, wherein the spatial regularity of real-world objects can enhance the efficiency of VWM encoding, but VWM cannot exploit spatial regularity to help organize sampled sequential information into meaningful integrations.

Disrupted Alpha-Ketoglutarate Homeostasis: Understanding Kidney Diseases from the View of Metabolism and Beyond.

Alpha-ketoglutarate (AKG) is a key intermediate of various metabolic pathways including tricarboxylic acid (TCA) cycle, anabolic and catabolic reactions of amino acids, and collagen biosynthesis. Meanwhile, AKG also participates in multiple signaling pathways related to cellular redox regulation, epigenetic processes, and inflammation response. Emerging evidence has shown that kidney diseases like diabetic nephropathy and renal ischemia/reperfusion injury are associated with metabolic disorders. In consistence with metabolic role of AKG, further metabolomics study demonstrated a dysregulated AKG level in kidney diseases. Intriguingly, earlier studies during the years of 1980s and 1990s indicated that AKG may benefit wound healing and surgery recovery. Recently, interests on AKG are arising again due to its protective roles on healthy ageing, which may shed light on developing novel therapeutic strategies against age-related diseases including renal diseases. This review will summarize the physiological and pathological properties of AKG, as well as the underlying molecular mechanisms, with a special emphasis on kidney diseases.

Extraordinary optical transmission in nano-bridged plasmonic arrays mimicking a stable weakly-connected percolation threshold.

Ultrasensitive sensors of various physical properties can be based on percolation systems, e.g., insulating media filled with nearly touching conducting particles. Such a system at its percolation threshold featuring the critical particle concentration, changes drastically its response (electrical conduction, light transmission, etc.) when subjected to an external stimulus. Due to the critical nature of this threshold, a given state at the threshold is typically very unstable. However, stability can be restored without significantly sacrificing the structure sensitivity by forming weak connections between the conducting particles. In this work, we employed nano-bridged nanosphere lithography to produce such a weakly connected percolation system. It consists of two coupled quasi-Babinet complementary arrays, one with weakly connected, and the other with disconnected metallic islands. We demonstrate via experiment and simulation that the physics of this plasmonic system is non-trivial, and leads to the extraordinary optical transmission at narrowly defined peaks sensitive to system parameters, with surface plasmons mediating this process. Thus, our system is a potential candidate for percolation effect based sensor applications. Promising detection schemes could be based on these effects.

Glycosylation-independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy.

Monoclonal antibody (mAb)-based blockade of programmed cell death 1 (PD-1) or its ligand to enable antitumor T-cell immunity has been successful in treating multiple tumors. However, the structural basis of the binding mechanisms of the mAbs and PD-1 and the effects of glycosylation of PD-1 on mAb interaction are not well understood. Here, we report the complex structure of PD-1 with toripalimab, a mAb that is approved by China National Medical Products Administration as a second-line treatment for melanoma and is under multiple Phase 1-Phase 3 clinical trials in both China and the US. Our analysis reveals that toripalimab mainly binds to the FG loop of PD-1 with an unconventionally long complementarity-determining region 3 loop of the heavy chain, which is distinct from the known binding epitopes of anti-PD-1 mAbs with structural evidences. The glycan modifications of PD-1 could be observed in three potential N-linked glycosylation sites, while no substantial influences were detected to the binding of toripalimab. These findings benefit our understanding of the binding mechanisms of toripalimab to PD-1 and shed light for future development of biologics targeting PD-1. Atomic coordinates have been deposited in the Protein Data Bank under accession code 6JBT.

Clinical and prognostic significance of OPN and VEGF expression in patients with non-small-cell lung cancer.

BACKGROUND: Osteopontin (OPN) and vascular endothelial growth factor (VEGF) play important roles in cancer progression and angiogenesis. In the current study we aimed to investigate the clinical significance of OPN and VEGF expression in patients with non-small-cell lung cancer (NSCLC) and to investigate their prognostic value for NSCLC. METHODS: Immunohistochemical staining was used to detect the expression of OPN and VEGF in 146 NSCLC patients undergoing surgical resection in our hospital between 2006 and 2008. The associations between OPN and VEGF expression and clinicopathological data were analyzed using chi-square test analysis. Survival analysis was performed using the Kaplan-Meier method. The prognostic values of OPN and VEGF were evaluated by univariate and multivariate Cox proportional hazard model analysis. RESULTS: OPN and VEGF expression was positive in 94 and 86 out of 146 NSCLC specimens, respectively. OPN expression was significantly associated with gender (P=0.002), TNM stage (P<0.001) and tumor differentiation (P=0.008). VEGF expression was significantly associated with TNM stage (P=0.015), tumor differentiation (P=0.032) and lymph-node status (P<0.001). There was a significant correlation between OPN and VEGF expression (P=0.035). Survival analysis indicated that OPN(+)/VEGF(+) patients had the worst prognosis. Furthermore, univariate and multivariate analysis suggested that tumor stage, lymph-node metastases, OPN expression and VEGF expression were independent prognostic factors for NSCLC. CONCLUSION: The data suggest that OPN and VEGF expressions could serve as prognostic factors for NSCLC.

Prognostic value of serum IL-17 and VEGF levels in small cell lung cancer.

OBJECTIVE: To explore the prognostic value of serum interleukin-17 (IL-17) and vascular endothelial growth factor (VEGF) levels in patients with small cell lung cancer (SCLC). MATERIALS AND METHODS: IL-17 and VEGF levels were determined by a commercially available ELISA method. RESULTS: Serum IL-17 and VEGF levels were higher in the SCLC group than the control group (p<0.001 and p<0.0001, respectively). In addition, there was a significant correlation between IL-17 and VEGF. The level of IL-17 showed significant correlations with tumor stage and tumor metastasis, while serum VEGF levels were significantly associated only with tumor metastasis. Univariate and multivariate analysis indicated that an elevated IL-17 level was an independent prognostic factor for shorter overall survival in SCLC. CONCLUSIONS: IL-17 may play an important role in tumor dissemination in SCLC patients and measurement of IL-17 could have useful prognostic value for worse overall survival in patients with SCLC.

Actin polymerization negatively regulates p53 function by impairing its nuclear import in response to DNA damage.

Actin, one of the most evolutionarily conservative proteins in eukaryotes, is distributed both in the cytoplasm and the nucleus, and its dynamics plays important roles in numerous cellular processes. Previous evidence has shown that actin interacts with p53 and this interaction increases in the process of p53 responding to DNA damage, but the physiological significance of their interaction remains elusive. Here, we show that DNA damage induces both actin polymerization and p53 accumulation. To further understand the implication of actin polymerization in p53 function, cells were treated with actin aggregation agent. We find that the protein level of p53 decrease. The change in p53 is a consequence of the polymeric actin anchoring p53 in the cytoplasm, thus impairing p53 nuclear import. Analysis of phosphorylation and ubiquitination of p53 reveals that actin polymerization promotes the p53 phosphorylation at Ser315 and reduces the stabilization of p53 by recruiting Aurora kinase A. Taken together, our results suggest that the actin polymerization serves as a negative modulator leading to the impairment of nuclear import and destabilization of p53. On the basis of our results, we propose that actin polymerization might be a factor participating in the process of orchestrating p53 function in response to DNA damage.

Serum miR-19a expression correlates with worse prognosis of patients with non-small cell lung cancer.

OBJECTIVES: The aim of this study was to investigate the expression levels of miR-19a in non-small cell lung cancer (NSCLC) tissue and serum, and to clarify the relationships of serum miR-19a expression with clinical factors and prognosis of NSCLC patients. METHODS: Expression levels of miR-19a in 25 paired NSCLC, paracancerous tissues and serum, and sera from 103 controls and 201 NSCLC patients were respectively detected using real-time quantitative PCR. RESULTS: Compared with the paracancerous tissue, miR-19a was overexpressed in NSCLC tissue (P = 0.006), and there was a strong correlation between expression levels of miR-19 in 25 paired sera and tissues (P = 0.001). Serum miR-19a expression in NSCLC patients was significantly upregulated compared with those in healthy individuals (P = 0.001). High serum miR-19a expression was significantly correlated with TNM stage and lymph node metastasis (P = 0.004 and 0.017, respectively). Survival analysis revealed that overall survival rate of patients with high serum miR-19a expression was significantly worse than those of patients with low serum miR-19a expression (hazard ratio = 1.438, 95% confidence interval 1.007-2.052, P = 0.046). CONCLUSION: High serum miR-19a expression may be an independent poor prognostic factor for survival in NSCLC patients.

Cu(II) removal from aqueous solution by Spartina alterniflora derived biochar.

A cost-effective biochar (SABC) was prepared from Spartina alterniflora by pyrolysis at low temperatures (≤ 500 °C) under anoxic conditions. The obtained biochar was examined for its ability to adsorb copper ions from aqueous solution and the Cu(II) removal mechanisms were explored. Cu(II) adsorption on SABC was found to fit well with Langmuir isotherm and pseudo-second-order kinetic model. The maximum Cu(II) adsorption capacity of SABC reached 48.49 mg g(-1), which is about 5 times higher than the raw biomass. Ion exchange had negligible effect on Cu(II) removal. Based on FTIR spectra and potentiometric titration, a complexation model including two acidic and one basic functional groups was proposed. However, metal ions complexation with the surface sites could not account for the uptake amounts of Cu(II) by SABC, alternative binding mechanisms might involve simultaneously.

ATRA inhibits the proliferation of DU145 prostate cancer cells through reducing the methylation level of HOXB13 gene.

All-trans retinoic acid (ATRA) has been widely investigated for treatments of many cancers including prostate cancer. HOXB13, silenced in androgen receptor-negative (AR(-)) prostate cancer cells, plays a role in AR(-) prostate cancer cell growth arrest. In this study we intended to elucidate the mechanisms that are involved in the proliferation inhibition of AR(-) prostate cancer cells triggered by ATRA. We discovered that ATRA was able to induce the growth arrest and to increase HOXB13 expression in AR(-) prostate cancer cells. Both EZH2 and DNMT3b participated in the repression of HOXB13 expression through an epigenetic mechanism involving DNA and histone methylation modifications. Specifically, EZH2 recruited DNMT3b to HOXB13 promoter to form a repression complex. Moreover, ATRA could upregulate HOXB13 through decreasing EZH2 and DNMT3b expressions and reducing their interactions with the HOXB13 promoter. Concurrently, the methylation level of the HOXB13 promoter was reduced upon the treatment of ATRA. Results from this study implicated a novel effect of ATRA in inhibition of the growth of AR(-) resistant human prostate cancer cells through alteration of HOXB13 expression as a result of epigenetic modifications.

G-actin participates in RNA polymerase II-dependent transcription elongation by recruiting positive transcription elongation factor b (P-TEFb).

Actin is a key regulator of RNA polymerase (Pol) II-dependent transcription. Positive transcription elongation factor b (P-TEFb), a Cdk9/cyclin T1 heterodimer, has been reported to play a critical role in transcription elongation. However, the relationship between actin and P-TEFb is still not clear. In this study, actin was found to interact with Cdk9, a catalytic subunit of P-TEFb, in elongation complexes. Using immunofluorescence and immunoprecipitation assays, Cdk9 was found to bind to G-actin through the conserved Thr-186 in the T-loop. Overexpression and in vitro kinase assays showed that G-actin promotes P-TEFb-dependent phosphorylation of the Pol II C-terminal domain. An in vitro transcription experiment revealed that the interaction between G-actin and Cdk9 stimulated Pol II transcription elongation. ChIP and immobilized template assays indicated that actin recruited Cdk9 to a transcriptional template in vivo and in vitro. Using cytokine IL-6-inducible p21 gene expression system, we revealed that actin recruited Cdk9 to endogenous gene. Moreover, overexpression of actin and Cdk9 increased histone H3 acetylation and acetylized histone H3 binding to a transcriptional template through the interaction with histone acetyltransferase, p300. Taken together, our results suggested that actin participates in transcription elongation by recruiting Cdk9 for phosphorylation of the Pol II C-terminal domain, and the actin-Cdk9 interaction promotes chromatin remodeling.