Different FeS Concentrations for Encapsulating ZIF-67 Nanomaterials toward the Enhanced Oxidation Evolution Reaction.

Due to the slow kinetic nature of the oxygen evolution reaction (OER), the development of electrocatalysts with high efficiency, stability, and economy for oxygen production using metal-organic framework (MOF) materials is still a challenging research topic. In this work, we chose the different concentrations of FeS adsorption to encapsulate metal cobalt-based ZIF-67 MOF for preparing a series of electrocatalysts (ZIF1FeSx, x = 0.2, 0.5, 0.75, and 1), which were mainly explored for the electrocatalytic OER. Among them, ZIF1FeS0.5 has excellent electrocatalytic activity for OER, which can be driven by low overpotentials of 276 and 349 mV at 10 and 50 mA cm-2 current densities, and more than 92% of the initial overpotential can be maintained after 100 h of continuous OER at 10 mA cm-2 current density. This is mainly due to the electronic interactions between the cobalt-based MOF and the FeS, which shift the electronic state of the active metal center to a higher valence state for increasing the number of active sites and enhancing the efficiency of electron transfer to facilitate the OER course. This work may contribute to the design of effective catalysts for the OER during the electrolysis of alkaline solutions.

Artificial Electron Channels Enable Contact Prelithiation of Li-Ion Battery Anodes with Ultrahigh Li-Source Utilization.

Contact prelithiation is widely used for compensating the initial capacity loss of lithium-ion batteries (LIBs). However, the low Li-source utilization suffering from the deteriorated contact interfaces results in cycling degeneration. Herein, Li-Ag alloy-based artificial electron channels (AECs) are established in Li source/graphite anode contact interfaces to promote Li-source conversion. Due to the shielding effect of the Li-Ag alloy (50 at. % Li) on Li-ion diffusion, the dry-state corrosion of contact interfaces is restricted. The unblocked electronic conduction across the AEC-involved interface not only facilitates the Li source conversion but also accelerates the prelithiation kinetics during the wet-state process, resulting in an ultrahigh Li-source utilization (90.7%). Thereby, implementing AEC-assisted prelithiation in a LiNi0.5Co0.2Mn0.3O2 pouch cell yields a 35.8% increase in energy density and stable cycling over 600 cycles. This finding affords significant insights into the construction of an efficient prelithiation technology toward the development of high-energy LIBs.

Excessive or sustained endoplasmic reticulum stress: one of the culprits of adipocyte dysfunction in obesity.

As the prevalence of obesity continues to rise globally, the research on adipocytes has attracted more and more attention. In the presence of nutrient overload, adipocytes are exposed to pressures such as hypoxia, inflammation, mechanical stress, metabolite, and oxidative stress that can lead to organelle dysfunction. Endoplasmic reticulum (ER) is a vital organelle for sensing cellular pressure, and its homeostasis is essential for maintaining adipocyte function. Under conditions of excess nutrition, ER stress (ERS) will be triggered by the gathering of abnormally folded proteins in the ER lumen, resulting in the activation of a signaling response known as the unfolded protein responses (UPRs), which is a response system to relieve ERS and restore ER homeostasis. However, if the UPRs fail to rescue ER homeostasis, ERS will activate pathways to damage cells. Studies have shown a role for disturbed activation of adipocyte ERS in the pathophysiology of obesity and its complications. Prolonged or excessive ERS in adipocytes can aggravate lipolysis, insulin resistance, and apoptosis and affect the bioactive molecule production. In addition, ERS also impacts the expression of some important genes. In view of the fact that ERS influences adipocyte function through various mechanisms, targeting ERS may be a viable strategy to treat obesity. This article summarizes the effects of ERS on adipocytes during obesity.

Utilization of tissue-free minimal residual disease testing in colorectal cancer patients from Asia and Middle East.

Introduction: The presence of minimal residual disease (MRD) after curative-intent surgery for early-stage cancers is associated with disease recurrence. Circulating tumour deoxyribonucleic acid (ctDNA) has emerged as a promising biomarker for MRD assessment in patients with colorectal cancer (CRC) who have undergone surgery or completed adjuvant therapy. MRD tests are already available for use in clinics; however, treatment decisions following MRD results obtained in routine practice are infrequently described. Methods: In this observational study, we report on the real-world clinical use of Guardant Reveal, a validated tissue-free MRD assay, in the first 215 consecutive patients (279 samples) with CRC tested in Asia and the Middle East. Results: Overall, 22% of patients had ctDNA detected in their first MRD test, and the frequency of ctDNA positivity increased with increasing tumour stage. 132 samples were tested with an earlier version of Guardant Reveal, one that assessed both genomic and epigenomic features. An updated version of the assay assesses only ctDNA methylation data and was used for the remaining 147 samples. In patients with stage II CRC, 71% of tests were ordered within 12 weeks after tumour resection, while for patients with stage III disease, 69% of tests were ordered after completion of all curative-intent treatment. Discussion: Clinical cases utilizing tissue-free MRD assessment are described.

A Portable Electrochemical Biosensor Based on an Amino-Modified Ionic Metal-Organic Framework for the One-Site Detection of Multiple Organophosphorus Pesticides.

Constructing stable, portable sensors and revealing their mechanisms is challenging. Ion metal-organic frameworks (IMOFs) are poised to serve as highly effective electrochemical sensors for detecting organophosphorus pesticides (OPs), leveraging their unique charge properties. In this work, an amino-modified IMOF was constructed and combined with near-field communication (NFC) technology to develop a portable, touchless, and battery-free electrochemical biosensor NH2-IMOF@CS@AChE. -NH2 in NH2-IMOF gives the framework a higher electropositivity compared to IMOF, enhancing the electrostatic attraction with acetylcholinesterase (AChE), which is beneficial for immobilizing AChE. Furthermore, the uncoordinated O atoms and the (CH3)2NH2+ groups in NH2-IMOF help to form stronger bonds with AChE through hydrogen bonds. The results showed a wide linear response range of 1 × 10-15 to 1 × 10-9 M and a low detection limit of 1.24 × 10-13 M for glyphosate (Gly) in the practical detection of OPs. Additionally, electrochemical biosensor arrays were constructed to effectively identify and distinguish multiple OPs on the basis of their unique differential pulse voltammetry (DPV) electrochemical signals. This work provides a simple and effective solution for on-site OP analysis and can be widely applied in food safety and water quality monitoring.

First-line zorifertinib for EGFR-mutant non-small cell lung cancer with central nervous system metastases: The phase 3 EVEREST trial.

BACKGROUND: Zorifertinib (AZD3759), an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with high blood-brain barrier penetration capability, demonstrated promising intracranial and systemic antitumor activity in phase 1 and 2 studies in central nervous system (CNS)-metastatic patients. METHODS: In this phase 3 EVEREST trial (ClinicalTrials.gov: NCT03653546), patients with EGFR-sensitizing mutations, advanced treatment-naive non-small cell lung cancer (NSCLC), and non-irradiated symptomatic or asymptomatic CNS metastases were randomized (1:1) to zorifertinib or first-generation EGFR-TKI (gefitinib or erlotinib; control). The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival (PFS) per RECIST1.1. FINDINGS: Overall, 439 patients were randomized (zorifertinib n = 220; control n = 219). Most patients had the EGFR L858R mutation (55%) or >3 CNS lesions (54%). Median PFS was significantly longer with zorifertinib versus control (9.6 versus 6.9 months; hazard ratio [HR], 0.719; 95% confidence interval [CI], 0.580-0.893; p = 0.0024). Zorifertinib significantly prolonged intracranial PFS versus control (BICR per modified RECIST1.1: HR, 0.467; 95% CI, 0.352-0.619; investigator per RANO-BM: HR, 0.627; 95% CI, 0.466-0.844). Overall survival (OS) was immature; the estimated median OS was 37.3 months with zorifertinib and 31.8 months with control (HR, 0.833; 95% CI, 0.524-1.283) in patients subsequently treated with third-generation EGFR-TKIs. Safety profiles were consistent with previously reported data for zorifertinib. CONCLUSIONS: Zorifertinib significantly improved systemic and intracranial PFS versus first-generation EGFR-TKIs; adverse events were manageable. Sequential use of zorifertinib and third-generation EGFR-TKIs showed the potential to prolong patients' survival. The results favor zorifertinib as a novel, well-validated first-line option for CNS-metastatic patients with EGFR-mutant NSCLC. FUNDING: This work was funded by Alpha Biopharma (Jiangsu) Co., Ltd., China.

The efficacy of socially assistive robots in improving children's pain and negative affectivity during needle-based invasive treatment: A systematic review and meta-analysis.

BACKGROUND: The ability of socially assistive robots (SARs) to treat dementia and Alzheimer's disease has been verified. Currently, to increase the range of their application, there is an increasing amount of interest in using SARs to relieve pain and negative emotions among children in routine medical settings. However, there is little consensus regarding the use of these robots. OBJECTIVE: This study aimed to evaluate the effect of SARs on pain and negative affectivity among children undergoing invasive needle-based procedures. DESIGN: This study was a systematic review and meta-analysis of randomized controlled trials that was conducted in accordance with the Cochrane Handbook guidelines. METHODS: The PubMed, CINAHL, Web of Science, Cochrane Library, Embase, CNKI, and WanFang databases were searched from inception to January 2024 to identify relevant randomized controlled trials (RCTs). We used the Cochrane Risk of Bias tool 2.0 (RoB2.0) to assess the risk of bias among the included studies, and we used RevMan 5.4 software to conduct the meta-analysis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used to assess the quality of the evidence. RESULTS: Ten RCTs involving 815 pediatric subjects were selected for this review and reported outcomes related to pain and emotions during IV placement, port needle insertion, flu vaccination, blood sampling, and dental treatment. Children undergoing needle-related procedures with SARs reported less anxiety (SMD= -0.36; 95% CI= -0.64, -0.09) and fewer distressed avoidance behaviors (SMD= -0.67; 95% CI= -1.04, -0.30) than did those receiving typical care. There were nonsignificant differences between these groups in terms of in pain (SMD = -0.02; 95% CI = - 0.81, 0.78) and fear (SMD = 0.38; 95% CI= -0.06, 0.82). The results of exploratory subgroup analyses revealed no statistically significant differences based on the intervention type of robots or anesthetic use. CONCLUSIONS: The use of SARs is a promising intervention method for alleviating anxiety and distress among children undergoing needle-related procedures. However, additional high-quality randomized controlled trials are needed to further validate these conclusions. TRIAL REGISTRATION: The protocol of this study has been registered in the database PROSPERO (registration ID: CRD42023413279).

Investigation of the effects of polyethylene microplastics at environmentally relevant concentrations on the plant-soil-microbiota system: A two-year field trial.

Microplastics are a potential threat to agricultural sustainability. However, the effects of microplastics at environmentally relevant concentrations on the plant-soil-microbiota system in realistic field conditions are largely unknown. Herein, we conducted a two-year field trial to study the effects of polyethylene (PE) microplastics at 0, 100, and 600 mg/kg on crop growth, soil properties, and the composition and function of microbial communities in a farmland with rice-wheat rotation. PE did not affect wheat growth but it increased the rice grain weight by 42.5 % at 600 mg/kg, and enhanced rice height by 35.4 % and 30.2 % at 100 and 600 mg/kg, respectively. The presence of PE significantly decreased soil available phosphorus during the wheat season, while it reduced soil total nitrogen, NH4+-N and available phosphorus during the rice season. There were five and sixteen bacterial orders identified changed by PE in wheat and rice soils, respectively. Specifically, PE at different concentrations differentially altered the abundances of sulfate-reducing bacteria Thermodesulfovibrionia, Thermoactinomycetales and Syntrophobacterales, and further modified soil sulfate respiration in wheat soils. During the rice season, PE (100 mg/kg) increased the abundance of Xanthomonadales by 98.0 % and enriched the functional groups of intracellular parasites, while PE (600 mg/kg) inhibited twelve cluster of orthologous group function classes and disturbed bacterial metabolism. This study suggests that PE exhibits a greater impact on the plant-soil-microbiota system during the rice season compared to the previous year's wheat season, highlighting the importance of crop type and cultivation practices in determining the environmental risks of microplastics in agroecosystems.

Predictor of Surgical Failure Following Transvaginal Mesh Repair Using Minimally Invasive Prolapse System Device (MIPS).

Background: The Minimally Invasive Prolapse System (MIPS) device, a novel single-incision transvaginal mesh, represents recent advancements in mesh technology, providing lightweight, biocompatible support for pelvic organ prolapse while reducing erosion, allowing for customization and improving surgical outcomes. This study aimed to identify factors associated with pelvic organ prolapse (POP) recurrence after transvaginal mesh (TVM) repair using the Minimally Invasive Prolapse System device. Methods: Two hundred and eighteen women with symptomatic stage II to IV POP underwent TVM. Preoperative and postoperative assessments included urinalyses and pelvic examinations using the POP quantification (POP-Q) staging system. Results: During a follow-up period of 12-46 months, 7 of 218 (3.2%) women experienced POP recurrence. Univariate analysis was conducted to identify predictors of surgical failure, revealing no significant differences in body mass index, POP stage, or preoperative urinary symptoms between the recurrence and success groups (p > 0.05). However, functional urethral length <20 mm based on urodynamics (p = 0.011), ICI-Q scores ≥7 (p = 0.012), and the first 60 surgical cases (p = 0.018) were significant predictors of surgical failure. Multivariate logistic regression confirmed these findings. Conclusions: Functional urethral length <20 mm, ICI-Q scores ≥7, and limited surgical experience were significant predictors of TVM failure using the Minimally Invasive Prolapse System kit. POP recurrence after mesh repair is less likely beyond the learning curve.

Microglia mediate memory dysfunction via excitatory synaptic elimination in a fracture surgery mouse model.

Cognitive impairment is a common issue among human patients undergoing surgery, yet the neural mechanism causing this impairment remains unidentified. Surgical procedures often lead to glial cell activation and neuronal hypoexcitability, both of which are known to contribute to postoperative cognitive dysfunction (POCD). However, the role of neuron-glia crosstalk in the pathology of POCD is still unclear. Through integrated transcriptomics and proteomics analyses, we found that the complement cascades and microglial phagocytotic signaling pathways are activated in a mouse model of POCD. Following surgery, there is a significant increase in the presence of complement C3, but not C1q, in conjunction with presynaptic elements. This triggers a reduction in excitatory synapses, a decline in excitatory synaptic transmission, and subsequent memory deficits in the mouse model. By genetically knockout out C3ar1 or inhibiting p-STAT3 signaling, we successfully prevented neuronal hypoexcitability and alleviated cognitive impairment in the mouse model. Therefore, targeting the C3aR and downstream p-STAT3 signaling pathways could serve as potential therapeutic approaches for mitigating POCD.

Development and validation of deep learning models for identifying the brand of pedicle screws on plain spine radiographs.

Background: In spinal revision surgery, previous pedicle screws (PS) may need to be replaced with new implants. Failure to accurately identify the brand of PS-based instrumentation preoperatively may increase the risk of perioperative complications. This study aimed to develop and validate an optimal deep learning (DL) model to identify the brand of PS-based instrumentation on plain radiographs of spine (PRS) using anteroposterior (AP) and lateral images. Methods: A total of 529 patients who received PS-based instrumentation from seven manufacturers were enrolled in this retrospective study. The postoperative PRS were gathered as ground truths. The training, validation, and testing datasets contained 338, 85, and 106 patients, respectively. YOLOv5 was used to crop out the screws' trajectory, and the EfficientNet-b0 model was used to develop single models (AP, Lateral, Merge, and Concatenated) based on the different PRS images. The ensemble models were different combinations of the single models. Primary outcomes were the models' performance in accuracy, sensitivity, precision, F1-score, kappa value, and area under the curve (AUC). Secondary outcomes were the relative performance of models versus human readers and external validation of the DL models. Results: The Lateral model had the most stable performance among single models. The discriminative performance was improved by the ensemble method. The AP + Lateral ensemble model had the most stable performance, with an accuracy of 0.9434, F1 score of 0.9388, and AUC of 0.9834. The performance of the ensemble models was comparable to that of experienced orthopedic surgeons and superior to that of inexperienced orthopedic surgeons. External validation revealed that the Lat + Concat ensemble model had the best accuracy (0.9412). Conclusion: The DL models demonstrated stable performance in identifying the brand of PS-based instrumentation based on AP and/or lateral images of PRS, which may assist orthopedic spine surgeons in preoperative revision planning in clinical practice.

Metabolic variation and oxidative stress responses of clams (Ruditapes philippinarum) perturbed by ofloxacin exposure.

Ofloxacin (OFL), one of the most widely used fluoroquinolone antibiotics, has been frequently detected in marine environments. Nonetheless, researchers are yet to focus on the effects of OFL on the benthos. In the present study, marine clams (Ruditapes philippinarum) were exposed to OFL (0.5, 50, and 500 µg/L) for 14 d, followed by a 7 d depuration period. The accumulation of OFL, antioxidative defense responses, neurotoxicity, burrowing behavior, and metabolomic changes in clams were evaluated. The results indicated that OFL could accumulate in clams, albeit with a low bioaccumulation capacity. The intermediate (50 µg/L) and high (500 µg/L) levels of OFL induced significant antioxidative responses in the gills and digestive glands of clams, mainly manifesting as the inhibition of catalase activities and the induction of superoxide dismutase and glutathione S-transferase activities, which ultimately elevated the content of malondialdehyde, causing oxidative damage. Furthermore, the significant induction of acetylcholinesterase activities was observed, coinciding with a significant increase in burrowing rates of clams. The high level of OFL affected glycerophospholipid, arachidonic acid, steroid hormone biosynthesis, unsaturated fatty acids biosynthesis, and glycolysis/glycogenesis metabolism. In conclusion, this study has contributed to the understanding of the physiological and biochemical effects and molecular toxicity mechanisms of OFL to marine bivalves.

SARS-CoV-2 Nsp15 antagonizes the cGAS-STING-mediated antiviral innate immune responses.

Coronavirus (CoV) Nsp15 is a viral endoribonuclease (EndoU) with a preference for uridine residues. CoV Nsp15 is an innate immune antagonist which prevents dsRNA sensor recognition and stress granule formation by targeting viral and host RNAs. SARS-CoV-2 restricts and delays the host antiviral innate immune responses through multiple viral proteins, but the role of SARS-CoV-2 Nsp15 in innate immune evasion is not completely understood. Here, we generate an EndoU activity knockout rSARS-CoV-2Nsp15-H234A to elucidate the biological functions of Nsp15. Relative to wild-type rSARS-CoV-2, replication of rSARS-CoV-2Nsp15-H234A was significantly decreased in IFN-responsive A549-ACE2 cells but not in its STAT1 knockout counterpart. Transcriptomic analysis revealed upregulation of innate immune response genes in cells infected with rSARS-CoV-2Nsp15-H234A relative to wild-type virus, including cGAS-STING, cytosolic DNA sensors activated by both DNA and RNA viruses. Treatment with STING inhibitors H-151 and SN-011 rescued the attenuated phenotype of rSARS-CoV-2Nsp15-H234A. SARS-CoV-2 Nsp15 inhibited cGAS-STING-mediated IFN-ß promoter and NF-κB reporter activity, as well as facilitated the replication of EV-D68 and NDV by diminishing cGAS and STING expression and downstream innate immune responses. Notably, the decline in cGAS and STING was also apparent during SARS-CoV-2 infection. The EndoU activity was essential for SARS-CoV-2 Nsp15-mediated cGAS and STING downregulation, but not all HCoV Nsp15 share the consistent substrate selectivity. In the hamster model, rSARS-CoV-2Nsp15-H234A replicated to lower titers in the nasal turbinates and lungs and induced higher innate immune responses. Collectively, our findings exhibit that SARS-CoV-2 Nsp15 serves as a host innate immune antagonist by targeting host cGAS and STING.

Effects of LDPE and PBAT plastics on soil organic carbon and carbon-enzymes: A mesocosm experiment under field conditions.

Although the effects of plastic residues on soil organic carbon (SOC) have been studied, variations in SOC and soil carbon-enzyme activities at different plant growth stages have been largely overlooked. There remains a knowledge gap on how various varieties of plastics affect SOC and carbon-enzyme activity dynamics during the different growing stages of plants. In this study, we conducted a mesocosm experiment under field conditions using low-density polyethylene and poly (butylene adipate-co-terephthalate) debris (LDPE-D and PBAT-D, 500-2000 µm (pieces), 0%, 0.05%, 0.1%, 0.2%, 0.5%, 1%, 2%), and low-density polyethylene microplastics (LDPE-M, 500-1000 µm (powder), 0%, 0.05%, 0.1%, 0.5%) to investigate SOC and C-enzyme activities (ß-xylosidase, cellobiohydrolase, ß-glucosidase) at the sowing, seedling, flowering and harvesting stages of soybean (Glycine Max). The results showed that SOC in the LDPE-D treatments significantly increased from the flowering to harvesting stage, by 12.69%-13.26% (p < 0.05), but significantly decreased in the 0.05% and 0.1% LDPE-M treatments from the sowing to seedling stage (p < 0.05). However, PBAT-D had no significant effect on SOC during the whole growing period. For C-enzyme activities, only LDPE-D treatments inhibited GH (17.22-38.56%), BG (46.7-66.53%) and CBH (13.19-23.16%), compared to treatment without plastic addition, from the flowering stage to harvesting stage. Meanwhile, C-enzyme activities and SOC responded nonmonotonically to plastic abundance and the impacts significantly varied among the growing stages, especially in treatments with PBAT-D (p < 0.05). These risks to soil organic carbon cycling are likely mediated by the effects of plastic contamination and degradation soil microbe. These effects are sensitive to plastic characteristics such as type, size, and shape, which, in turn, affect the biogeochemical and mechanical interactions involving plastic particles. Therefore, further research on the interactions between plastic degradation processes and the soil microbial community may provide better mechanistic understanding the effect of plastic contamination on soil organic carbon cycling.

Global-local aware Heterogeneous Graph Contrastive Learning for multifaceted association prediction in miRNA-gene-disease networks.

Unraveling the intricate network of associations among microRNAs (miRNAs), genes, and diseases is pivotal for deciphering molecular mechanisms, refining disease diagnosis, and crafting targeted therapies. Computational strategies, leveraging link prediction within biological graphs, present a cost-efficient alternative to high-cost empirical assays. However, while plenty of methods excel at predicting specific associations, such as miRNA-disease associations (MDAs), miRNA-target interactions (MTIs), and disease-gene associations (DGAs), a holistic approach harnessing diverse data sources for multifaceted association prediction remains largely unexplored. The limited availability of high-quality data, as vitro experiments to comprehensively confirm associations are often expensive and time-consuming, results in a sparse and noisy heterogeneous graph, hindering an accurate prediction of these complex associations. To address this challenge, we propose a novel framework called Global-local aware Heterogeneous Graph Contrastive Learning (GlaHGCL). GlaHGCL combines global and local contrastive learning to improve node embeddings in the heterogeneous graph. In particular, global contrastive learning enhances the robustness of node embeddings against noise by aligning global representations of the original graph and its augmented counterpart. Local contrastive learning enforces representation consistency between functionally similar or connected nodes across diverse data sources, effectively leveraging data heterogeneity and mitigating the issue of data scarcity. The refined node representations are applied to downstream tasks, such as MDA, MTI, and DGA prediction. Experiments show GlaHGCL outperforming state-of-the-art methods, and case studies further demonstrate its ability to accurately uncover new associations among miRNAs, genes, and diseases. We have made the datasets and source code publicly available at https://github.com/Sue-syx/GlaHGCL.

The clinicopathological significance and prognostic impact of 14-3-3σ/stratifin expression on patients with surgically resectable intrahepatic cholangiocarcinoma.

INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer after hepatocellular carcinoma. Through data mining of publicly available iCCA transcriptomic datasets from the Gene Expression Omnibus, we identified SFN as the most significantly up-regulated gene in iCCA compared to normal tissue, focusing on the Gene Ontology term "cell proliferation" (GO:0008283). SFN encodes the 14-3-3σ protein, also known as stratifin, which plays crucial roles in various cellular processes. MATERIALS AND METHODS: Immunohistochemistry was used to assess stratifin expression in 182 patients with localized iCCAs undergoing surgical resection. Patients were divided into low and high expression groups, and the association between stratifin expression and clinicopathological features was analyzed. Univariate and multivariate survival analyses were performed to assess overall survival (OS), disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS). RESULTS: Elevated stratifin expression in iCCAs was significantly associated with the absence of hepatitis, positive surgical margins, advanced primary tumor stages, and higher histological grades (all p ≤ 0.011). Survival analyses demonstrated a significant negative association between stratifin expression and all prognostic indicators, including OS, DSS, LRFS, and MeFS (all p ≤ 0.0004). Multivariate analysis revealed that stratifin overexpression was significantly correlated with poorer outcomes in terms of DSS, LRFS, and MeFS (all p < 0.001). CONCLUSIONS: These findings suggest that stratifin may play a crucial role in iCCA oncogenesis and tumor progression, serving as a potential novel prognostic biomarker.

Hydrogelation of peptides and carnosic acid as regulators of adaptive immunity against postoperative recurrence of cutaneous melanoma.

The in-situ activation of adaptive immunity at the surgical site has demonstrated remarkable efficacy in inhibiting various forms of tumour recurrence and even holds the promise of a potential cure. However, extensive research and bioinformatic analysis conducted in this study have unveiled the formidable challenge posed by melanoma-intrinsic ß-catenin signaling, which hinders the infiltration of cytotoxic T-lymphocytes (CTLs) and their subsequent anti-tumour action. To overcome this obstacle, a ß-catenin antagonist called carnosic acid (CA) was co-assembled with a RADA-rich peptide to create a nanonet-derived hydrogel known as Supra-gelδCA. This injectable hydrogel is designed to be retained at the surgical site while simultaneously promoting hemostasis. Importantly, Supra-gelδCA directly releases CA to the site of residual tumour lesions, thereby enhancing infiltration of CTLs and subsequently activating adaptive immunity. Consequently, it effectively suppresses postoperative recurrence of skin cutaneous melanoma (SKCM) in vivo. Collectively, the presented Supra-gelδCA not only provides an efficacious immunotherapy strategy for regulating adaptive immunity by overcoming the obstacle posed by melanoma-intrinsic ß-catenin signaling-induced absence of CTLs but also offers a clinically translatable hydrogel that revolutionizes post-surgical management of SKCM.

Anoikis-Related Long Non-Coding RNA Signatures to Predict Prognosis and Immune Infiltration of Gastric Cancer.

Anoikis is a distinct type of programmed cell death and a unique mechanism for tumor progress. However, its exact function in gastric cancer (GC) remains unknown. This study aims to investigate the function of anoikis-related lncRNA (ar-lncRNA) in the prognosis of GC and its immunological infiltration. The ar-lncRNAs were derived from RNA sequencing data and associated clinical information obtained from The Cancer Genome Atlas. Pearson correlation analysis, differential screening, LASSO and Cox regression were utilized to identify the typical ar-lncRNAs with prognostic significance, and the corresponding risk model was constructed, respectively. Comprehensive methods were employed to assess the clinical characteristics of the prediction model, ensuring the accuracy of the prediction results. Further analysis was conducted on the relationship between immune microenvironment and risk features, and sensitivity predictions were made about anticancer medicines. A risk model was built according to seven selected ar-lncRNAs. The model was validated and the calibration plots were highly consistent in validating nomogram predictions. Further analyses revealed the great accuracy of the model and its ability to serve as a stand-alone GC prognostic factor. We subsequently disclosed that high-risk groups display significant enrichment in pathways related to tumors and the immune system. Additionally, in tumor immunoassays, notable variations in immune infiltrates and checkpoints were noted between different risk groups. This study proposes, for the first time, that prognostic signatures of ar-lncRNA can be established in GC. These signatures accurately predict the prognosis of GC and offer potential biomarkers, suggesting new avenues for basic research, prognosis prediction and personalized diagnosis and treatment of GC.

Relieving effect of jiao-tune of 5-element music on negative emotions in patients with decompensated hepatitis B virus cirrhosis: A randomized and controlled experiment study.

BACKGROUND: Depression and anxiety are common in patients with decompensated hepatitis B virus (HBV) cirrhosis. This study aimed to evaluate the relieving effects of the jiao-tune of 5-element music on negative emotions in patients with decompensated HBV cirrhosis. METHODS: The patients were randomly allocated into the control group (standard nursing care) and the jiao-tune group (standard nursing care plus a 2-month course of music therapy with the jiao-tune of 5-element music). The negative emotions of patients were assessed before intervention treatment and at the end of the 2-month follow-up using the Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS). RESULTS: The analysis included 209 patients, with 102 in the control group and 107 in the jiao-tune group, all of whom returned their completed questionnaires. Baseline clinical characteristics and length of hospital stay were comparable between 2 groups. Before intervention treatment, there were no significant differences in SAS score (55.78 ±â€…5.64 vs 56.47 ±â€…3.28) and SDS score (65.13 ±â€…3.12 vs 64.48 ±â€…4.47) between the jiao-tune group and control group. After 2-month follow-up, the jiao-tune group had a significantly lower SAS score (53.17 ±â€…5.61) and SDS score (61.28 ±â€…1.52) compared with the control group (55.49 ±â€…3.37 and 63.08 ±â€…2.76), there were significant differences between 2 groups (P < .001). CONCLUSIONS: The jiao-tune of 5-element music can relieve the negative emotions in patients with decompensated HBV cirrhosis.

Base-mediated synthesis of aryl enol ethers from α-aryl allylic alcohols and arylsulfonium salts.

A concise synthesis of aryl enol ethers from allylic alcohols and arylsulfonium salts by simply using an inorganic base as a mediator is described. The reaction enabled the facile conversion of various α-aryl allylic alcohols into the corresponding aryl enol ethers in good yields with excellent selectivity. The results demonstrated that both symmetric triarylsulfonium triflate and 10-methyl-5-aryl-5,10-dihydrophenothiazin-5-ium salts were effective arylation reagents for the base-initiated selective O-arylation and isomerization of α-aryl allylic alcohols. This reaction represents the first use of arylsulfonium salts as arylation reagents to access aryl enol ethers directly from allylic alcohols.