Reversible pH-Gated MXene Membranes with Ultrahigh Mono-/Divalent-Ion Selectivity.

Artificial ion channel membranes hold high promise in water treatment, nanofluidics, and energy conversion, but it remains a great challenge to construct such smart membranes with both reversible ion-gating capability and desirable ion selectivity. Herein, we constructed a smart MXene-based membrane via p-phenylenediamine functionalization (MLM-PPD) with highly stable and aligned two-dimensional subnanochannels, which exhibits reversible ion-gating capability and ultrahigh metal ion selectivity similar to biological ion channels. The pH-sensitive groups within the MLM-PPD channel confers excellent reversible Mg2+-gating capability with a pH-switching ratio of up to 100. The mono/divalent metal-ion selectivity up to 1243.8 and 400.9 for K+/Mg2+ and Li+/Mg2+, respectively, outperforms other reported membranes. Theoretical calculations combined with experimental results reveal that the steric hindrance and stronger PPD-ion interactions substantially enhance the energy barrier for divalent metal ions passing through the MLM-PPD, and thus leading to ultrahigh mono/divalent metal-ion selectivity. This work provides a new strategy for developing artificial-ion channel membranes with both reversible ion-gating functionality and high-ion selectivity for various applications.

Soluble Programmed Cell Death 1 Protein Is a Promising Biomarker to Predict Severe Liver Inflammation in Chronic Hepatitis B Patients.

Background and Aims: Liver inflammation is important in guiding the initiation of antiviral treatment and affects the progression of chronic hepatitis B(CHB). The soluble programmed cell death 1 protein (sPD-1) was upregulated in inflammatory and infectious diseases and correlated with disease severity. We aimed to investigate the correlation between serum sPD-1 levels and liver inflammation in CHB patients and their role in indicating liver inflammation. Methods: 241 CHB patients who underwent liver biopsy were enrolled. The correlation between sPD-1 levels and the degree of liver inflammation was analyzed. Univariate and multivariate logistic regression analyses were performed to analyze independent variables of severe liver inflammation. Binary logistic regression analysis was conducted to construct a predictive model for severe liver inflammation, and the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic accuracy of the predictive model. Results: sPD-1 was highest in CHB patients with severe liver inflammation, which was higher than that in CHB patients with mild or moderate liver inflammation (P < 0.001). Besides, sPD-1 was weakly correlated with AST (r = 0.278, P < 0.001). Multivariable analysis showed that sPD-1 was an independent predictor of severe liver inflammation. The predictive model containing sPD-1 had areas under the ROC (AUROCs) of 0.917 and 0.921 in predicting severe liver inflammation in CHB patients and CHB patients with ALT ≤ 1× upper limit of normal (ULN), respectively. Conclusions: Serum sPD-1 level is associated with liver inflammation in CHB patients, and high levels of sPD-1 reflect severe liver inflammation. Serum sPD-1 is an independent predictor of severe liver inflammation and shows improved diagnostic accuracy when combined with other clinical indicators.

The effect of joint position sense therapy on chronic shoulder pain with central sensitization.

BACKGROUND: Chronic shoulder pain is a common musculoskeletal problem associated with unreleased pain and functional dysfunction that can evolve into central sensitization. Some forms of manual therapy may exacerbate pain and central sensitization. This study investigated the impact of joint position sense therapy (JPST), a moderate joint proprioception training technique, on central sensitization, shoulder functional dysfunction, and pain in patients with chronic shoulder pain compared with more intense exercises or aggressive manual therapies. METHODS: We assessed the pressure pain threshold (PPT) in 30 patients with and 30 patients without chronic shoulder pain. The assessment focused on 4 muscle sites: deltoid, upper trapezius, brachioradialis, and tibialis anterior. Thirty patients with chronic shoulder pain were randomly divided into the JPST and control groups. The JPST group underwent additional shoulder joint position-sense training. The efficiency outcomes were the disabilities of the arm, shoulder, and hand questionnaire, visual analog scale (VAS), and PPT, evaluated at baseline and after the intervention. RESULTS: Significant differences were observed in the PPT values at the brachioradialis (P < .05), deltoid (P < .01), and trapezius (P < .001) among the non-chronic and chronic groups, but not in the tibialis anterior muscle (P > .05). Although both control and JPST interventions effectively improved the disabilities of the arm, shoulder, and hand questionnaire score, pain intensity, and PPT values in the upper limb, the outcomes in the JPST group were significantly different from those in the control group. CONCLUSIONS: Generalized hyperalgesia changes limited to the upper limbs were observed in patients with chronic shoulder pain. JPST has beneficial effects on pain control and functional dysfunction in patients with chronic shoulder pain.

Identification of a prognostic signature based on five ferroptosis-related genes for diffuse large B-cell lymphoma.

BACKGROUND: Therapies for diffuse large B-cell lymphoma (DLBCL) are limited due to the diverse gene expression profiles and complicated immune microenvironments, making it an aggressive lymphoma. Beyond this, researches have shown that ferroptosis contributes to tumorigenesis, progression, and metastasis. We thus are interested to dissect the connection between ferroptosis and disease status of DLBCL. We aim at generating a valuable prognosis gene signature for predicting the status of patients of DLBCL, with focus on ferroptosis-related genes (FRGs). OBJECTIVE: To examine the connection between ferroptosis-related genes (FRGs) and clinical outcomes in DLBCL patients based on public datasets. METHODS: An expression profile dataset for DLBCL was downloaded from GSE32918 (https://www.ncbi.nlm.nih.gov/geo/ query/acc.cgi?acc=gse32918), and a ferroptosis-related gene cluster was obtained from the FerrDb database (http://www. zhounan.org/ferrdb/). A prognostic signature was developed from this gene cluster by applying a least absolute shrinkage and selection operator (LASSO) Cox regression analysis to GSE32918, followed by external validation. Its effectiveness as a biomarker and the prognostic value was determined by a receiver operator characteristic curve mono factor analysis. Finally, functional enrichment was evaluated by the package Cluster Profiler of R. RESULTS: Five ferroptosis-related genes (FRGs) (GOP1, GPX2, SLC7A5, ATF4, and CXCL2) associated with DLBCL were obtained by a multivariate analysis. The prognostic power of these five FRGs was verified by TCGA (https://xenabrowser.net/datapages/?dataset=TCGA.DLBC.sampleMap%2FHiSeqV2_PANCAN&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A44) and GEO (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse 32918) datasets, with ROC analyses. KEGG and GO analyses revealed that upregulated genes in the high-risk group based on the gene signature were enriched in receptor interactions and other cancer-related pathways, including pathways related to abnormal metabolism and cell differentiation. CONCLUSION: The newly developed signature involving GOP1, GPX2, SLC7A5, ATF4, and CXCL2 has the potential to serve as a prognostic biomarker. Furthermore, our results provide additional support for the contribution of ferroptosis to DLBCL.

The role of extracellular vesicle immune checkpoints in cancer.

Immune checkpoints (ICPs) play a crucial role in regulating the immune response. In the tumor, malignant cells can hijack the immunosuppressive effects of inhibitory ICPs to promote tumor progression. Extracellular vesicles (EVs) are produced by a variety of cells and contain bioactive molecules on their surface or within their lumen. The expression of ICPs has also been detected on EVs. In vitro and in vivo studies have shown that extracellular vesicle immune checkpoints (EV ICPs) have immunomodulatory effects and are involved in tumor immunity. EV ICPs isolated from the peripheral blood of cancer patients are closely associated with the tumor progression and the prognosis of cancer patients. Blocking inhibitory ICPs has been recognized as an effective strategy in cancer treatment. However, the efficacy of immune checkpoint inhibitors (ICIs) in cancer treatment is hindered by the emergence of therapeutic resistance, which limit their widespread use. Researchers have demonstrated that EV ICPs are correlated with clinical response to ICIs therapy and were involved in therapeutic resistance. Therefore, it's essential to investigate the immunomodulatory effects, underlying mechanisms, and clinical significance of EV ICPs in cancer. This review aims to comprehensively explore these aspects. We have provided a comprehensive description of the cellular origins, immunomodulatory effects, and clinical significance of EV ICPs in cancer, based on relevant studies.

Robust Model Watermarking for Image Processing Networks via Structure Consistency.

The intellectual property of deep networks can be easily "stolen" by surrogate model attack. There has been significant progress in protecting the model IP in classification tasks. However, little attention has been devoted to the protection of image processing models. By utilizing consistent invisible spatial watermarks, the work [1] first considered model watermarking for deep image processing networks and demonstrated its efficacy in many downstream tasks. Its success depends on the hypothesis that if a consistent watermark exists in all prediction outputs, that watermark will be learned into the attacker's surrogate model. However, when the attacker uses common data augmentation attacks (e.g., rotate, crop, and resize) during surrogate model training, it will fail because the underlying watermark consistency is destroyed. To mitigate this issue, we propose a new watermarking methodology, "structure consistency", based on which a new deep structure-aligned model watermarking algorithm is designed. Specifically, the embedded watermarks are designed to be aligned with physically consistent image structures, such as edges or semantic regions. Experiments demonstrate that our method is more robust than the baseline in resisting data augmentation attacks. Besides that, we test the generalization ability and robustness of our method to a broader range of adaptive attacks.

PointCAT: Contrastive Adversarial Training for Robust Point Cloud Recognition.

Notwithstanding the prominent performance shown in various applications, point cloud recognition models have often suffered from natural corruptions and adversarial perturbations. In this paper, we delve into boosting the general robustness of point cloud recognition, proposing Point-Cloud Contrastive Adversarial Training (PointCAT). The main intuition of PointCAT is encouraging the target recognition model to narrow the decision gap between clean point clouds and corrupted point clouds by devising feature-level constraints rather than logit-level constraints. Specifically, we leverage a supervised contrastive loss to facilitate the alignment and the uniformity of hypersphere representations, and design a pair of centralizing losses with dynamic prototype guidance to prevent features from deviating outside their belonging category clusters. To generate more challenging corrupted point clouds, we adversarially train a noise generator concurrently with the recognition model from the scratch. This differs from previous adversarial training methods that utilized gradient-based attacks as the inner loop. Comprehensive experiments show that the proposed PointCAT outperforms the baseline methods, significantly enhancing the robustness of diverse point cloud recognition models under various corruptions, including isotropic point noises, the LiDAR simulated noises, random point dropping, and adversarial perturbations. Our code is available at: https://github.com/shikiw/PointCAT.

A novel brain-controlled prosthetic hand method integrating AR-SSVEP augmentation, asynchronous control, and machine vision assistance.

Background and objective: The brain-computer interface (BCI) system based on steady-state visual evoked potentials (SSVEP) is expected to help disabled patients achieve alternative prosthetic hand assistance. However, the existing study still has some shortcomings in interaction aspects such as stimulus paradigm and control logic. The purpose of this study is to innovate the visual stimulus paradigm and asynchronous decoding/control strategy by integrating augmented reality technology, and propose an asynchronous pattern recognition algorithm, thereby improving the interaction logic and practical application capabilities of the prosthetic hand with the BCI system. Methods: An asynchronous visual stimulus paradigm based on an augmented reality (AR) interface was proposed in this paper, in which there were 8 control modes, including Grasp, Put down, Pinch, Point, Fist, Palm push, Hold pen, and Initial. According to the attentional orienting characteristics of the paradigm, a novel asynchronous pattern recognition algorithm that combines center extended canonical correlation analysis and support vector machine (Center-ECCA-SVM) was proposed. Then, this study proposed an intelligent BCI system switch based on a deep learning object detection algorithm (YOLOv4) to improve the level of user interaction. Finally, two experiments were designed to test the performance of the brain-controlled prosthetic hand system and its practical performance in real scenarios. Results: Under the AR paradigm of this study, compared with the liquid crystal display (LCD) paradigm, the average SSVEP spectrum amplitude of multiple subjects increased by 17.41%, and the signal-noise ratio (SNR) increased by 3.52%. The average stimulus pattern recognition accuracy was 96.71 ± 3.91%, which was 2.62% higher than the LCD paradigm. Under the data analysis time of 2s, the Center-ECCA-SVM classifier obtained 94.66 ± 3.87% and 97.40 ± 2.78% asynchronous pattern recognition accuracy under the Normal metric and the Tolerant metric, respectively. And the YOLOv4-tiny model achieves a speed of 25.29fps and a 96.4% confidence in the prosthetic hand in real-time detection. Finally, the brain-controlled prosthetic hand helped the subjects to complete 4 kinds of daily life tasks in the real scene, and the time-consuming were all within an acceptable range, which verified the effectiveness and practicability of the system. Conclusion: This research is based on improving the user interaction level of the prosthetic hand with the BCI system, and has made improvements in the SSVEP paradigm, asynchronous pattern recognition, interaction, and control logic. Furthermore, it also provides support for BCI areas for alternative prosthetic control, and movement disorder rehabilitation programs.

CD2AP is a potential prognostic biomarker of renal clear cell carcinoma.

BACKGROUND: CD2-associated protein (CD2AP) is a podocyte-associated gene and its reduced expression is associated with the development of proteinuria and glomerulosclerosis. However, few studies have focused on the correlation between the expression and prognosis of CD2AP in renal clear cell carcinoma (ccRCC). Therefore, we aimed to assess the regulation of CD2AP expression and prognostic value in ccRCC. METHODS: Multiple databases were employed to examine the expression of CD2AP in ccRCC. RT-qPCR, Western Blot and immunohistochemistry were used to validate CD2AP expression in different cell lines and tissue samples. Kaplan-Meier analysis and ROC curve analysis were performed on the predictive prognostic performance of CD2AP. COX regression was used to construct CD2AP-related prognostic models. The TIMER and TISIDB databases were used to analyze the correlation of tumor-infiltrating immune cells with gene expression, mutations, somatic copy number variation, and immune molecules. Mass spectrometry was used to detect methylation status of the promoter CpG site of CD2AP in multiple cells. RESULTS: We found that CD2AP expression was downregulated in ccRCC and its lower expression level was correlation with worse patient prognosis, higher tumor stage and grade and distant metastasis through analysis of databases, ccRCC cell lines and clinical tissue samples. Moreover, database and mass spectrometry techniques identified and validated cg12968598 hypermethylation as one of the key reasons for the downregulation of CD2AP expression. CD2AP expression was also associated with macrophage and neutrophil infiltration. CONCLUSIONS: Taken together, our results suggest that CD2AP can be used as a diagnostic and prognostic biomarker in ccRCC patients and that DNA hypermethylation plays an important role in reducing CD2AP expression.

Incidence and survival of second primary non-Hodgkin lymphoma: A Surveillance, Epidemiology, and End Results-based cohort study.

BACKGROUND: The aim of this study was to investigate patient survival and factors associated with survival in second primary non-Hodgkin lymphoma (NHL) compared with the first primary NHL. METHODS: The retrospective cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Demographic characteristics, histological types, Ann Arbor stage, and treatment information were collected. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with overall survival (OS) and cancer-specific survival (CSS) in the first and second primary NHLs. RESULTS: Of 318,168 cases followed for 5 years, 299,248 patients developed the first primary NHL and 18,920 patients developed the second primary NHL. This study identified a rising incidence of first and second primary NHL from 2000 to 2014. For the second primary NHL, the OS risk was higher when compared to the first primary NHL (HR: 1.13, 95% CI: 1.11 to 1.15, P <0.001). Risk factors that negatively affected OS in the first primary NHL included being male, over 40 years of age, certain marital statuses, specific histological types, and advanced disease stages. In contrast, being of White race and having histological types such as Follicular Lymphoma (FL), Marginal Zone Lymphoma (MZL), and mantle B-cell NHL were associated with better OS outcomes. Treatments like surgery, radiation therapy, and chemotherapy were associated with a lower risk of OS and CSS in the first primary NHL. For the second primary NHL, the detrimental risk factors were similar but also included being over the age of 60. Certain histological types showed a lower OS risk relative to diffuse Large B-cell Lymphoma (DLBCL). While surgery and chemotherapy were beneficial for OS, radiation therapy did not improve survival in second primary NHL cases. Notably, undergoing chemotherapy for the first primary cancer increased the OS risk in the second primary NHL, whereas surgery and radiation seemed to offer a protective effect against OS risk in the second primary NHL (all P <0.05). CONCLUSION: Our findings emphasize the need for tailored strategies in managing the second primary NHL, given the distinct survival patterns and risk factor profiles compared to the first primary NHL. Future research should aim to further elucidate these differences to improve prognosis and treatment approaches for second primary NHL patients.

Physical therapy for acute and sub-acute low back pain: A systematic review and expert consensus.

OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.

Investigating causal relationships between the gut microbiota and inflammatory skin diseases: A Mendelian randomization study.

BACKGROUND: Numerous inflammatory skin diseases are associated with the gut microbiota. Studies of the association between gut microbiota and inflammatory skin diseases have yielded conflicting results owing to confounding factors, and the causal relationship between them remains undetermined. METHODS: Two-sample Mendelian randomization (MR) was used to examine the association between gut microbiota and four common inflammatory skin diseases: acne, psoriasis, urticaria and atopic dermatitis. The summary statistics of the gut microbiota from the largest available genome-wide association study meta-analysis (n = 13,266) conducted by the MiBioGen consortium along with the summary statistics of the four diseases were obtained from the FinnGen consortium. Causal relationships were assessed using the inverse variance weighted (IVW), weighted median, MR-Egger and maximum likelihood methods, and several sensitivity analyses were performed to ensure the accuracy of the results. Finally, reverse and multivariable MR analyses were performed to verify the robustness of the results. RESULTS: We found causal associations of Bacteroidaceae [odds ratio (OR), 2.25; 95% confidence interval (CI), 1.48-3.42; pivw = 0.0001], Allisonella (OR, 1.42; 95% CI, 1.18-1.70; pivw = 0.0002) and Bacteroides (OR, 2.25; 95% CI, 1.48-3.42; pivw = 0.0001) with acne, the Eubacterium fissicatena group with psoriasis (OR, 1.22; 95% CI, 1.10-1.35; pivw = 0.0002) and Intestinibacter with urticaria (OR, 1.28; 95% CI, 1.13-1.45; pivw = 0.0001). These results were corrected for a false discovery rate. Sensitivity analyses were performed to validate the robustness of the associations and reverse MR confirmed that the results were not influenced by the reverse effect. CONCLUSION: Our study revealed that some gut microbiota are risk factors for inflammatory skin diseases, providing new information on potential therapeutic targets. Additionally, a possible association with the gut-skin axis was confirmed. Further research is required to elucidate the mechanisms underlying these relationships.

Identification of HSP90B1 in pan-cancer hallmarks to aid development of a potential therapeutic target.

Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future.

Oxidation of emerging contaminants by S(IV) activated ferrate: Identification of reactive species.

Studies on the Fe(VI)/S(IV) process have focused on improving the efficiency of emerging contaminants (ECs) degradation under alkaline conditions. However, the performance and mechanisms under varying pH levels remain insufficiently investigated. This tudy delved into the efficiency and mechanism of Fe(VI)/S(IV) process using sulfamethoxazole (SMX) and ibuprofen (IBU) as model contaminants. We found that pH was crucial in governing the generation of reactive species, and both Fe(V/IV) and SO4•- were identified in the reaction system. Specifically, an increase in pH favored the formation of SO4•-, while the formation of Fe(VI) to Fe(V/IV) became more significant at lower pH. At pH 3.2, Fe(III) resulting from the Fe(VI) self-decay reactedwith HSO3-to produce SO4•-and •OH. Under near-neutral conditions, the coexistance of Fe(V/IV) and SO4•- in abundance contributed to the optimal oxidation of both pollutants in the Fe(VI)/S(IV) process, with the removal exceeding 74% in 5 min. Competitive quenching experiments showed that the contributions of Fe(V/IV) to SMX and IBU destruction dimished, while the contributions of radicals increased with an increase in pH. However, this evolution was slower during SMX degradation compared to IBU degradation. A comprehensive understnding of pH as the key factor is essential for the optimization of the sulfite-activated Fe(VI) oxidation process in water treatment.

ControlFace: Feature Disentangling for Controllable Face Swapping.

Face swapping is an intriguing and intricate task in the field of computer vision. Currently, most mainstream face swapping methods employ face recognition models to extract identity features and inject them into the generation process. Nonetheless, such methods often struggle to effectively transfer identity information, which leads to generated results failing to achieve a high identity similarity to the source face. Furthermore, if we can accurately disentangle identity information, we can achieve controllable face swapping, thereby providing more choices to users. In pursuit of this goal, we propose a new face swapping framework (ControlFace) based on the disentanglement of identity information. We disentangle the structure and texture of the source face, encoding and characterizing them in the form of feature embeddings separately. According to the semantic level of each feature representation, we inject them into the corresponding feature mapper and fuse them adequately in the latent space of StyleGAN. Owing to such disentanglement of structure and texture, we are able to controllably transfer parts of the identity features. Extensive experiments and comparisons with state-of-the-art face swapping methods demonstrate the superiority of our face swapping framework in terms of transferring identity information, producing high-quality face images, and controllable face swapping.

LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior.

This study aimed to clarify the role of la-related protein 1 (LARP1) in cell cycle progression and metastatic behavior of cultured gastric carcinoma (GC) cells. To do that, LARP1 expression was detected in clinical GC tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The cell viability, apoptosis, cell cycle, migration, invasion, and cell growth were examined using a Cell Counting Kit-8, Annexin V-FITC staining, propidium iodide staining, Transwell migration and invasion assays, and colony formation assays after LARP1 knockdown. Phosphatidyl inositol 3-kinase (PI3K) and AKT1 mRNA and protein expression levels of PI3K, p-AKT1, AKT1, p-BAD, p-mTOR, and p21 in si-LARP1 transfected GC cells were determined using qRT-PCR and western blotting. Here, we've shown that LARP1 expression was upregulated in human GC tissues and KATO III cells. LARP1 knockdown inhibited GC cell proliferation, cell cycle progression, migration, invasion, and colony formation and promoted apoptosis. In si-LARP1-transfected KATO III cells, the mRNA expression levels of PI3K and AKT1, PI3K protein expression, and the p-AKT1/AKT1 ratio were significantly suppressed. p-mTOR and p-BAD were significantly decreased, whereas p21 was significantly increased in si-LARP1-transfected KATO III cells. In conclusion LARP1 knockdown induces apoptosis and inhibits cell cycle progression and metastatic behavior via PI3K/AKT1 signaling in GC cells.

Chimeric antigen receptor-based natural killer cell immunotherapy in cancer: from bench to bedside.

Immunotherapy has rapidly evolved in the past decades in the battle against cancer. Chimeric antigen receptor (CAR)-engineered T cells have demonstrated significant success in certain hematologic malignancies, although they still face certain limitations, including high costs and toxic effects. Natural killer cells (NK cells), as a vital component of the immune system, serve as the "first responders" in the context of cancer development. In this literature review, we provide an updated understanding of NK cell development, functions, and their applications in disease therapy. Furthermore, we explore the rationale for utilizing engineered NK cell therapies, such as CAR-NK cells, and discuss the differences between CAR-T and CAR-NK cells. We also provide insights into the key elements and strategies involved in CAR design for engineered NK cells. In addition, we highlight the challenges currently encountered and discuss the future directions in NK cell research and utilization, including pre-clinical investigations and ongoing clinical trials. Based on the outstanding antitumor potential of NK cells, it is highly likely that they will lead to groundbreaking advancements in cancer treatment in the future.

Selective formation of high-valent iron in Fenton-like system for emerging contaminants degradation under near-neutral and high-salt conditions.

In view of the near-neutral and high-salt conditions, the Fenton technology with hydroxyl radicals (HO•) as the main reactive species is difficult to satisfy the removal of trace emerging contaminants (ECs) in pharmaceutical sewage. Here, a layered double hydroxide FeZn-LDH was prepared, and the selective formation of ≡Fe(IV)=O in Fenton-like system was accomplished by the chemical environment regulation of the iron sites and the pH control of the microregion. The introduced zinc can increase the length of Fe-O bond in the FeZn-LDH shell layer by 0.22 Å compared to that in Fe2O3, which was conducive to the oxygen transfer process between ≡Fe(III) and H2O2, resulting in the ≡Fe(IV)=O formation. Besides, the amphoteric hydroxide Zn(OH)2 can regulate the pH of the FeZn-LDH surface microregion, maintaining reaction pH at around 6.5-7.5, which could avoid the quenching of ≡Fe(IV)=O by H+. On the other hand, owing to the anti-interference of ≡Fe(IV)=O and the near-zero Zeta potential on the FeZn-LDH surface, the trace ECs can also be effectively degraded under high-salt conditions. Consequently, the process of ≡Fe(IV)=O generation in FeZn-LDH system can satisfy the efficient removal of ECs under near-neutral and high-salt conditions.

Prediction of pancreatic fibrosis by dual-energy CT-derived extracellular volume fraction: Comparison with MRI.

OBJECTIVES: To investigate the correlation between dual-energy CT (DECT) and MRI measurements of the extracellular volume fraction (ECV) and to assess the accuracy of both methods in predicting pancreatic fibrosis (PF). METHODS: We retrospectively analyzed 43 patients who underwent pancreatectomy and preoperative pancreatic DECT and MRI between November 2018 and May 2022. The ECV was calculated using the T1 relaxation time (for MR-ECV) or absolute enhancement (for DECT-ECV) at equilibrium phase (180 s after contrast injection in our study). Pearson coefficient and Bland-Altman analysis were used to compare the correlation between the two ECVs, Spearman correlations were used to investigate the association between imaging parameters and PF, Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of the ECVs for advanced fibrosis (F2-F3), and multivariate logistic regression analysis was used to examine the relationship between PF and imaging parameters. RESULTS: There was a strong correlation between DECT- and MR-derived ECVs (r = 0.948; p < 0.001). The two ECVs were positively correlated with PF (DECT: r = 0.647, p < 0.001; MR: r = 0.614, p < 0.001), and the mean values were 0.34 ± 0.08 (range: 0.22-0.62) and 0.35 ± 0.09 (range: 0.24-0.66), respectively. The area under the operating characteristic curve (AUC) for subjects with advanced fibrosis diagnosed by ECV was 0.86 for DECT-ECV and 0.87 for MR-ECV. Multivariate logistic regression analysis showed that the DECT-ECV was an independent predictor of PF. CONCLUSIONS: The ECV could be an effective predictor of histological fibrosis, and DECT is equivalent to MRI for characterizing pancreatic ECV changes.

Deep Image Matting With Sparse User Interactions.

Image matting is a fundamental and challenging problem in computer vision and graphics. Most existing matting methods leverage a user-supplied trimap as an auxiliary input to produce good alpha matte. However, obtaining high-quality trimap itself is arduous. Recently, some hint-free methods have emerged, however, the matting quality is still far behind the trimap-based methods. The main reason is that, some hints for removing semantic ambiguity and improving matting quality are essential. Apparently, there is a trade-off between interaction cost and matting quality. To balance performance and user-friendliness, we propose an improved deep image matting framework which is trimap-free and only needs sparse user click or scribble interaction to minimize the needed auxiliary constraints while still allowing interactivity. Moreover, we introduce uncertainty estimation that predicts which parts need polishing and conduct uncertainty-guided refinement. To trade off runtime against refinement quality, users can also choose different refinement modes. Experimental results show that our method performs better than existing trimap-free methods and comparably to state-of-the-art trimap-based methods with minimal user effort. Finally, we demonstrate the extensibility of our framework to video human matting without any structure modification, by adding optical flow-based sparse hint propagation and temporal consistency regularization imposed on the single frame.