Self-Adhesive Electronic Skin with Bio-Inspired 3D Architecture for Mechanical Stimuli Monitoring and Human-Machine Interactions.

Recent development of wearable devices is revolutionizing the way of artificial electronic skins (E-skin), physiological health monitoring and human-machine interactions (HMI). However, challenge remains to fit flexible electronic devices to the human skin with conformal deformation and identifiable electrical feedback according to the mechanical stimuli. Herein, an adhesive E-skin is developed that can firmly attach on the human skin for mechanical stimuli perception. The laser-induced adhesive layer serves as the essential component to ensure the conformal attachment of E-skin on curved surface, which ensures the accurate conversion from mechanical deformation to precise electrical readouts. Especially, the 3D architecture facilitates the non-overlapping outputs that bi-directional joint bending and distinguishes strain/pressure. The optimized E-skin with bio-inspired micro-cilia exhibited significantly improved sensing performances with sensitivity of 0.652 kPa-1 in 0-4 kPa and gauge factor of 8.13 for strain (0-15%) with robustness. Furthermore, the adhesive E-skin can distinguish inward/outward joint bending in non-overlapping behaviors, allowing the establishment of ternary system to expand communication capacity for logic outputs such as effective Morse code and intelligent control. It expects that the adhesive E-skin can serve as a functional bridge between human and electrical terminals for applications from daily mechanical monitoring to efficient HMI.

α­Fetoprotein­positive hepatoid adenocarcinoma of the stomach and a new classification: A case report.

α-Fetoprotein (AFP)-producing gastric carcinoma (AFPGC) is a rare subtype of gastric cancer (GC) with controversial classification methods. Hepatoid adenocarcinoma of the stomach (HAS) is another rare subtype of GC. Its definition intersects with that of AFPGC, but it is much rarer. The present report describes the case of an elderly patient with GC and AFPGC and HAS features in a serum test and pathology, respectively, and proposes a new classification of GC subtypes based on histological and AFP-producing features. A 75-year-old woman presented with a history of polydipsia and polyuria for over a decade and dizziness for 1 day. Serum AFP levels gradually elevated from 183.70 to 397.70 ng/ml in 1 month after the patient's first clinic visit. Subsequent pathological findings from endoscopic biopsy samples confirmed a hepatoid focus with positive immunohistochemical staining for AFP. The patient underwent a laparoscopic-assisted radical total gastrectomy and esophagojejunal Roux-en-Y anastomosis, and the serum AFP levels decreased to the normal range after the surgery. The present case indicates the diagnostic value of both the serum AFP level and pathological examinations in the diagnosis of AFPGC and HAS, and also highlights the contemporary circumstances of the vague classification based on different criteria for these two subtypes. Furthermore, the present report proposes a new classification considering both histological and AFP-producing features (using both serum biomarkers and immunohistochemistry tests) to cover all cases encompassed by AFPGC and HAS under all definition methods. This new method would give more precise diagnoses and add value to the subsequent treatment decision-making.

Investigating the genetic causal relationship between breast cancer and endometrial cancer: A two-sample Mendelian randomization study.

Observational studies have consistently shown a correlation between breast cancer (BC) and endometrial cancer (EC). Despite these findings, the causal relationship between these cancers has not been clearly defined. This research employed a bidirectional two-sample Mendelian randomization to explore the genetic causality between BC and EC. Genetic instruments for BC were derived from the Breast Cancer Association Consortium genome-wide association studies summary statistics, while for EC, data were sourced from the Endometrial Cancer Association Consortium, the Epidemiology of Endometrial Cancer Consortium, and the UK Biobank. The primary analytical method was inverse-variance weighted. Additional analyses, such as MR-Egger and weighted median, were conducted to validate the robustness of our findings from multiple perspectives. The MR-Egger intercept test was conducted to examine potential pleiotropy, whereas Cochrane Q test was implemented to assess heterogeneity. A leave-one-out analysis was conducted to assess the sensitivity of the observed association. Our analysis identified a bidirectional genetic causal relationship between estrogen receptor-positive breast cancer (ER+BC) and EC. Inverse-variance weighted analysis indicated an odds ratio of 1.0686 (95% confidence interval: 1.0029-1.1386, P = .0403) from ER+BC to EC and an odds ratio of 1.0692 (95% confidence interval: 1.0183-1.1225, P = .0071) from EC to ER+BC. No significant horizontal pleiotropy was detected. This study confirms a bidirectional genetic link between ER+BC and EC, suggesting shared genetic etiologies and possibly linked pathophysiological pathways. Understanding the genetic interplay between ER+BC and EC can enhance strategies for the precise prevention and screening of these prevalent cancers, potentially leading to improved clinical outcomes and management of secondary primary malignancies.

Influence of the continuing COVID-19 epidemic on sleep quality and psychological status of healthcare workers in private institutions.

BACKGROUND: On January 22, 2020, Macao reported its first case of coronavirus disease 2019 (COVID-19) infection. By August 2021, the situation had escalated into a crisis of community transmission. In response, the government launched a recruitment campaign seeking assistance and services of healthcare workers (HCWs) from the private sector throughout Macao. These participants faced concerns about their own health and that of their families, as well as the responsibility of maintaining public health and wellness. This study aims to determine whether the ongoing epidemic has caused them physical and psychological distress. AIM: To examine the influence of COVID-19 on the sleep quality and psychological status of HCWs in private institutions in Macao during the pandemic. METHODS: Data were collected from December 2020 to January 2022. Two consecutive surveys were conducted. The Pittsburgh Sleep Quality Index (PSQI) scale, Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) were employed as investigation tools. RESULTS: In the first-stage survey, 32% of HCWs experienced a sleep disorder, compared to 28.45% in the second-stage survey. A total of 31.25% of HCWs in the first-stage survey and 28.03% in the second had varying degrees of anxiety. A total of 50.00% of HCWs in the first-stage survey and 50.63% in the second experienced varying degrees of depression. No difference in PSQI scores, SAS scores, or SDS scores were observed between the two surveys, indicating that the COVID-19 epidemic influenced the sleep quality and psychological status of HCWs. The negative influence persisted over both periods but did not increase remarkably for more than a year. However, a positive correlation was observed between the PSQI, SAS, and SDS scores (r = 0.428-0.775, P < 0.01), indicating that when one of these states deteriorated, the other two tended to deteriorate as well. CONCLUSION: The sleep quality, anxiety, and depression of HCWs in private institution in Macao were affected by the COVID-19 epidemic. While these factors did not deteriorate significantly, the negative effects persisted for a year and remained noteworthy.

A Solidified Controllable Resin System Suitable for Fracture Cavity Formation Plugging and Its Performance Characterization.

Thermosetting resins have good temperature resistance and high strength and have been widely used as plugging agents in oil fields. However, the current resin materials have high costs, and unmodified thermosetting resins are brittle or have deteriorated properties such as flame retardancy after curing to form a crosslinked network structure. In this study, the resin was modified via physical blending. The curing strength and temperature resistance were used as the main indicators. The resin matrix, curing agent, rheology modifier, and filling materials were modified and formulated optimally to form a high-strength resin gel plugging system. The resin gel system exhibited good fluidity and pumpability. When the shear rate was 200 s-1 at 25 °C, the initial viscosity was 300-400 mPa·s. The viscosity gradually decreased with increasing shear rate, and the apparent viscosity had good long-term stability at room temperature. A contamination test of different types of drilling fluids on the resin gel system showed that this system had good anti-contamination capability and could maintain a high curing strength even after being contaminated. At the same time, the system exhibited good plugging capability. A wedge-shaped fracture with an inlet size of 7 mm and an outlet size of 5 mm was plugged at 12.84 MPa for 10 min without leakage. A sand-filling pipe (with a diameter of 3.8 cm and pipe length of 30 cm) connected to the pipeline with a 6 mm outlet was subjected to a constant pressure of 11.29 MPa and plugged for 8 min before breaking through. Therefore, it exhibited good capability for plugging fissures and cavities. The resin gel leakage-plugging system has significant potential to realize effective plugging of the deep large-fracture leakage layer.

High-Strength Controllable Resin Plugging Agent and Its Performance Evaluation for Fractured Formation.

Lost circulation is a common and complicated situation in drilling engineering. Serious lost circulation may lead to pressure drop in the well, affect normal drilling operations, and even cause wellbore instability, formation fluid flooding into the wellbore, and blowout. Therefore, appropriate preventive and treatment measures need to be taken to ensure the safe and smooth operation of drilling operations. So, it is necessary to conduct in-depth research on the development and performance of the plugging materials. In this study, urea formaldehyde resin with high temperature resistance and strength was used as the main raw material, and the curing conditions were optimized and adjusted by adding a variety of additives. The curing time, compressive strength, temperature resistance, and other key performance indexes of the resin plugging agent were studied, and a resin plugging agent system with excellent plugging performance was prepared. The formula is as follows: 25% urea formaldehyde resin +1% betaine +1% silane coupling agent KH-570 + 3% ammonium chloride +1% hexamethylenetetramine +1% sodium carboxymethyl cellulose. The optimal curing temperature is between 60 and 80 °C, with a controllable curing time of 1-3 h. Experimental studies examined the rheological and curing properties of the resin plugging agent system. The results showed that the viscosity of the high-strength curable resin system before curing remained stable with increasing shear rates. Additionally, the storage modulus and loss modulus of the resin solutions increased with shear stress, with the loss modulus being greater than the storage modulus, indicating a viscous fluid. The study also investigated the effect of different salt ion concentrations on the curing effect of the resin plugging system. The results showed that formation water containing Na+ at concentrations between 500 mg/L and 10,000 mg/L increased the resin's curing strength and reduced curing time. However, excessively high concentrations at lower temperatures reduced the curing strength. Formation water containing Ca2+ increased the curing time of the resin plugging system and significantly impacted the curing strength, reducing it to some extent. Moreover, the high-strength curable resin plugging agent system can effectively stay in various fracture types (parallel, wedge-shaped) and different fracture sizes, forming a high-strength consolidation under certain temperature conditions for effective plugging. In wedge-shaped fractures with a width of 10 mm, the breakthrough pressure of the high-strength curable resin plugging agent system reached 8.1 MPa. As the fracture width decreases, the breakthrough pressure increases, reaching 9.98 MPa in wedge-shaped fractures with an outlet fracture width of 3 mm, forming a high-strength plugging layer. This research provides new ideas and methods for solving drilling fluid loss in fractured loss zones and has certain application and promotion value.

Reduced Radial Artery Occlusion in Transradial Cerebral Angiography: Key Predictive Factors and Preventive Measures from a Single-Center Study of 543 Patients.

BACKGROUND The transradial approach (TRA) for cerebral angiography and neurointerventional treatment has gained popularity, but the narrow diameter and weak pulsation of the radial artery lower the initial puncture success rate compared to femoral artery puncture. This retrospective study from a single center evaluated the incidence of and factors associated with radial artery occlusion (RAO) in 543 patients who underwent transradial approach (TRA) for cerebral angiography. MATERIAL AND METHODS We included 543 patients who underwent TRA from July 2021 to February 2024. Ultrasound was used to determine whether the radial artery was occluded. Relevant clinical data were recorded to assess the incidence of and factors affecting RAO. RESULTS At 24 h after DSA, we performed ultrasound imaging. The patients were divided into an RAO group (n=32) and a non-RAO group (n=511). Results showed that RAO was significantly higher in patients who did not have add heparin to the antispasmodic agents, and they were more likely to have needed more than 3 radial artery puncture attempts, and tended to have received an 11-cm radial artery sheath with the Cordis puncture needles (all P<0.05). Multiple regression logistic analysis showed that adding heparin to the antispasmodic agents (OR=0.076, 95% CI: 0.018-0.321, P<0.001), having fewer than 3 radial artery puncture attempts (OR=0.245, 95% CI: 0.111-0.541, P<0.001), using a 16-cm radial artery sheath (OR=0.195, 95% CI: 0.067-0.564, P=0.003), and using Terumo puncture needles (OR=0.325, 95% CI: 0.148-0.717, P=0.005) can reduce the incidence of radial artery occlusion. CONCLUSIONS Our center found that adding heparin to the antispasmodic agents reduced the number of radial artery punctures attempts, and using a 16-cm radial artery sheath significantly lowered the incidence of early RAO after transradial cerebral angiography.

Scytinostromabambusinum sp. nov. (Russulales, Basidiomycota) in China evidenced by morphological characteristics and phylogenetic analyses.

Background: Wood-rotting fungi as an important group within the Basidiomycota are known for their ecological role in the forest ecosystem in terms of decaying living and dead trees and recycling nutrients in forest ecosystems. Many new species were revealed in the last five years. In the present study, during an ongoing study on Scytinostroma, a new species of Scytinostroma was found from China. It is described and illustrated on the basis of the morphological and phylogenetic evidence. New information: Scytinostromabambusinum sp. nov. is described as a new species, based on morphological and molecular evidence. It is characterised by annual, resupinate and broadly ellipsoid basidiomata with white to cream hymenophore, a dimitic hyphal structure with generative hyphae bearing simple septa, the presence of cystidioles and amyloid basidiospores measuring 5.5-7 × 4-5.3 µm. Phylogeny, based on molecular data of ITS and nLSU sequences, shows that the new species forms an independent lineage and is different in morphology from the existing species of Scytinostroma.

ACTIVATION OF KLOTHO/SIRT1 SIGNALING PATHWAY ATTENUATES MYOCARDIAL ISCHEMIA REPERFUSION INJURY IN DIABETIC RATS.

ABSTRACT: Diabetes and myocardial ischemia reperfusion (MIR) injury are characterized by oxidative stress, inflammation, autophagy disorders, and cardiac contractile dysfunction. Klotho and SIRT1 regulate the level of oxidative stress to participate in the regulation of many physiological functions such as cell survival, aging, apoptosis, autophagy, mitochondrial biogenesis, and inflammation. We hypothesized that the activation of Klotho/SIRT1 signaling pathway could attenuate MIR in diabetic rats. Type 1 diabetes and MIR injury model were established to examine this hypothesis in vivo . Primary rat cardiomyocytes and H9c2 cells were exposed to high glucose conditions and hypoxia/reoxygenation (H/R) insult in vitro . Hemodynamic parameters of heart function, myocardial infarct size, oxidative stress, markers of MIR injury or cell viability, and the mRNA and protein expression of Klotho and SIRT1 were measured. There was lower expression of Klotho and SIRT1 in diabetic MIR hearts than in nondiabetic rats, as well as significantly increased oxidative stress levels and decreased autophagy levels. Recombinant Klotho (rKlotho) protein and the SIRT1 agonist SRT1720 could significantly attenuate MIR injury in diabetes by activating Klotho/SIRT1 signaling pathway to reduce oxidative stress and restore autophagy levels. These findings suggest that the Klotho/SIRT1 pathway plays an important role in MIR injury in diabetic rats, and rKlotho protein and agonist SRT1720 have therapeutic potential for alleviating diabetic myocardial IR injury by activating Klotho/SIRT1 to reduce oxidative stress and restore autophagy levels.

Roles of O-GlcNAcylation in Mitochondrial Homeostasis and Cardiovascular Diseases.

Protein posttranslational modifications are important factors that mediate the fine regulation of signaling molecules. O-linked ß-N-acetylglucosamine-modification (O-GlcNAcylation) is a monosaccharide modification on N-acetylglucosamine linked to the hydroxyl terminus of serine and threonine of proteins. O-GlcNAcylation is responsive to cellular stress as a reversible and posttranslational modification of nuclear, mitochondrial and cytoplasmic proteins. Mitochondrial proteins are the main targets of O-GlcNAcylation and O-GlcNAcylation is a key regulator of mitochondrial homeostasis by directly regulating the mitochondrial proteome or protein activity and function. Disruption of O-GlcNAcylation is closely related to mitochondrial dysfunction. More importantly, the O-GlcNAcylation of cardiac proteins has been proven to be protective or harmful to cardiac function. Mitochondrial homeostasis is crucial for cardiac contractile function and myocardial cell metabolism, and the imbalance of mitochondrial homeostasis plays a crucial role in the pathogenesis of cardiovascular diseases (CVDs). In this review, we will focus on the interactions between protein O-GlcNAcylation and mitochondrial homeostasis and provide insights on the role of mitochondrial protein O-GlcNAcylation in CVDs.

Two Debaryomyces hansenii strains as starter cultures for improving the nutritional and sensory quality of dry-cured pork belly.

Dry-cured meat products are gaining attention owing to their distinctive sensory characteristics and health benefits. In this study, two Debaryomyces hansenii strains were investigated for their potential as starter cultures for dry-cured pork belly products. After preliminary screening, these D. hansenii strains, namely, S20 and S26, both exhibiting with excellent aroma-producing capacity in a dry-cured meat model, were selected as single-strain starter cultures. For comparison, a non-inoculated control was also evaluated. In S20- and S26-inoculated pork belly, yeast dominated the microbiota and improved microbiological safety by suppressing Enterobacteriaceae growth. Compared with the non-inoculated control, the inoculated pork belly yielded higher hardness and redness (a*) values. Starter culture inoculation accelerated proteolysis in pork belly, improving the content of total free amino acids (TFFAs) and several essential free amino acids (Thr, Val, Met, Ile, Leu, and Phe) at the end of processing. Moreover, the inoculated samples exhibited higher levels of fat oxidation-derived aldehydes as well as esters, acids, alcohols and other compounds than the non-inoculated control at the end of the 95-day ripening period. Overall, these findings provide new insights into the application of D. hansenii isolated from dry-cured ham to dry-cured pork belly.

Low-dose IL-2 treatment confers anti-inflammatory effect against subarachnoid hemorrhage in mice.

Objective: Subarachnoid hemorrhage (SAH) was a stroke with high occurrence and mortality. At the early stage, SAH patients have severe cerebral injury which is contributed by inflammation. In this study, we aimed to explore the anti-inflammation effect of low-dose IL-2 in SAH mice. Methods: The 12-week-old C57BL/6J male mice were conducted with SAH surgery (Internal carotid artery puncture method). Different dose of IL-2 was injected intraperitoneally for 1 h, 1 day, and 2 days after SAH. Single-cell suspension and flow cytometry were used for the test of regulatory T (Treg) cells. Immunofluorescence staining was used to investigate the phenotypic polarization of microglia and inflammation response around neurons. Enzyme-Linked Immuno-sorbent Assay (ELISA) was applied to detect the level of pro-inflammatory factors. Results: Low-dose IL-2 could enrich the Treg cells and drive the microglia polarizing to M2. The level of pro-inflammatory factors, IL-1α, IL-6, and TNF-α decreased in the low-dose IL-2 group. The inflammation response around neurons was attenuated. Low-dose IL-2 could increase the number of Treg cells, which could exert a neuroprotective effect against inflammation after SAH. Conclusion: Low-dose IL-2 had the potential to be an effective clinical method to inhibit inflammation after SAH.

Study on the treatment of osteoarthritis by acupuncture combined with traditional Chinese medicine based on pathophysiological mechanism: A review.

Osteoarthritis (OA) is a major contributor to disability and social costs in the elderly. As the population ages and becomes increasingly obese, the incidence of the disease is higher than in previous decades. In recent years, important progress has been made in the causes and pathogenesis of OA pain. Modern medical treatment modalities mainly include the specific situation of the patient and focus on the core treatment, including self-management and education, exercise, and related weight loss. As an important part of complementary and alternative medicine, TCM has remarkable curative effect, clinical safety, and diversity of treatment methods in the treatment of OA. Traditional Chinese Medicine treatment of OA has attracted worldwide attention. Therefore, this article will study the pathophysiological mechanism of OA based on modern medicine, and explore the treatment of OA by acupuncture combined with Chinese Medicine.

Tanshinone IIA induces ER stress and JNK activation to inhibit tumor growth and enhance anti-PD-1 immunotherapy in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) remains at the forefront of new cancer cases, and there is an urgent need to find new treatments or improve the efficacy of existing therapies. In addition to the application in the field of cerebrovascular diseases, recent studies have revealed that tanshinone IIA (Tan IIA) has anticancer activity in a variety of cancers. PURPOSE: To investigate the potential anticancer mechanism of Tan IIA and its impact on immunotherapy in NSCLC. METHODS: Cytotoxicity and colony formation assays were used to detect the Tan IIA inhibitory effect on NSCLC cells. This research clarified the mechanisms of Tan IIA in anti-tumor and programmed death-ligand 1 (PD-L1) regulation by using flow cytometry, transient transfection, western blotting and immunohistochemistry (IHC) methods. Besides, IHC was also used to analyze the nuclear factor of activated T cells 1 (NFAT2) expression in NSCLC clinical samples. Two animal models including xenograft mouse model and Lewis lung cancer model were used for evaluating tumor suppressive efficacy of Tan IIA. We also tested the efficacy of Tan IIA combined with programmed cell death protein 1 (PD-1) inhibitors in Lewis lung cancer model. RESULTS: Tan IIA exhibited good NSCLC inhibitory effect which was accompanied by endoplasmic reticulum (ER) stress response and increasing Ca2+ levels. Moreover, Tan IIA could suppress the NFAT2/ Myc proto oncogene protein (c-Myc) signaling, and it also was able to control the Jun Proto-Oncogene(c-Jun)/PD-L1 axis in NSCLC cells through the c-Jun N-terminal kinase (JNK) pathway. High NFAT2 levels were potential factors for poor prognosis in NSCLC patients. Finally, animal experiments data showed a stronger immune activation phenotype, when we performed treatment of Tan IIA combined with PD-1 monoclonal antibody. CONCLUSION: The findings of our research suggested a novel mechanism for Tan IIA to inhibit NSCLC, which could exert anti-cancer effects through the JNK/NFAT2/c-Myc pathway. Furthermore, Tan IIA could regulate tumor PD-L1 levels and has the potential to improve the efficacy of PD-1 inhibitors.

Feasibility of early radial artery occlusion recanalization and reuse through transradial access for neuroendovascular procedures.

BACKGROUND: Radial artery occlusion (RAO) remains a significant limitation of neuroendovascular procedures peformed through transradial access (TRA) when radial artery needs to be reused. Instances of early RAO recanalization to successfully complete neuroendovascular procedures have been rarely documented. MATERIALS AND METHODS: Documents and imaging data were extracted retrospectively for all patients who underwent TRA diagnostic angiography and neuroendovascular procedures in our center from June 2022 to February 2023. The patients with early RAO who required repeat TRA were included. RESULTS: A total of 46 patients underwent repeat TRA, and 13 consecutive patients who experienced early RAO after angiography as confirmed by ultrasonography were enrolled in this study. The occluded radial arteries were successfully recanalized, and subsequent neuroendovascular procedures were carried out successful. During an average follow-up time of 7.1 months, no patients exhibited symptomatic RAO, dissection, hematoma or pseudoaneurysm. CONCLUSIONS: Early RAO recanalization and reused for neuroendovascular procedures through TRA is feasible. A visually guided and stable puncture process plays a crucial role in successfully recanalizing early RAO.

Progress in treatment of facial neuritis by acupuncture combined with medicine from the perspective of modern medicine: A review.

Facial neuritis is a common clinical disease with high incidence, also known as Bell palsy or idiopathic facial nerve paralysis, which is an acute onset of peripheral facial neuropathy. In modern medicine, there have been obstacles to the effective treatment of facial neuritis. At present, the clinical use of Western medicine treatment is also a summary of clinical experience, the reason is that the cause of facial neuritis is unknown. Facial neuritis belongs to the category of "facial paralysis" in traditional Chinese medicine. For thousands of years, Chinese medicine has accumulated a lot of relevant treatment experience in the process of diagnosis and treatment. At the same time, traditional Chinese medicine, acupuncture and the combination of acupuncture and medicine play an important role in the treatment of facial neuritis. This article discusses the treatment of facial neuritis with acupuncture combined with Chinese medicine, based on the research progress of modern medicine. In this review, we provide an overview of the effectiveness of acupuncture and medication combinations and facial neuritis with current studies investigating acupuncture and medication combinations in the treatment of facial neuritis.

CERS4 predicts positive anti-PD-1 response and promotes immunomodulation through Rhob-mediated suppression of CD8+Tim3+ exhausted T cells in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the main malignant tumors with high mortality and short survival time. Immunotherapy has become the standard treatment for advanced NSCLC, but it has the problems of drug resistance and low response rate. Therefore, obtaining effective biomarkers to predict and enhance immune checkpoint inhibitors (ICIs) efficacy in NSCLC is important. Sphingolipid metabolism is recently found to be closely involved in tumor immunotherapy. CERS4, an important sphingolipid metabolizing enzyme, is positively correlated with the efficacy of anti-PD-1 therapy for NSCLC. Upregulation of CERS4 expression could improve the efficacy of anti-PD-1 therapy for NSCLC. High expression of CERS4 could downregulate the expression of Rhob in tumor. Significantly, the ratio of CD4+/CD8+ T cell increased and the ratio of Tim-3+/CD8+ T cell decreased in spleen and peripheral blood cells. When Rhob was knocked out, the efficacy of PD-1 mAb treatment increased, and the frequency of Tim-3+ CD8+ T cell decreased. This finding further confirmed the role of sphingolipid metabolites in regulating the immunotherapeutic function of NSCLC. These metabolites may improve the efficacy of PD-1 mAb in NSCLC by regulating the CERS4/Rhob/Tim-3 axis. Overall, this study provided a potential and effective target for predicting and improving the efficacy of ICIs for NSCLC. It also provided a new perspective for the study on the mechanisms of ICIs resistance for NSCLC.

Implications of CRNDE in prognosis, tumor immunity, and therapeutic sensitivity in low grade glioma patients.

BACKGROUND: Colorectal tumor differentially expressed (CRNDE) is specifically expressed in human brains and is the most highly expressed lncRNA in gliomas. Nevertheless, its implications in low grade glioma (LGG) are still indistinct. This study presented systematic analyses of CRNDE in LGG biology. METHODS: We retrospectively retrieved TCGA, CGGC and GSE16011 LGG cohorts. Survival analysis was conducted for evaluating the prognostic significance of CRNDE in LGG. A CRNDE-based nomogram was established, and its predictive performance was verified. Signaling pathways underlying CRNDE were analyzed through ssGSEA and GSEA approaches. The abundance of immune cells and activity of cancer-immunity cycle were estimated with ssGSEA approach. Immune checkpoints, HLAs, chemokines, and immunotherapeutic response indicators (TIDE, and TMB) was quantified. U251 and SW1088 cells were transfected with specific shRNAs of CRNDE, and flow cytometry (apoptosis) and western blot (ß-catenin and Wnt5a) assays were conducted. RESULTS: Up-regulated CRNDE was found in LGG, and was linked to unfavorable clinical outcomes. The CRNDE-based nomogram enabled to accurately predict patients' prognosis. High CRNDE expression was linked to more genomic variations, activity of tumorigenic pathways, tumor immunity (increase in infiltration of immune cells, expression of immune checkpoints, HLAs and chemokines, and cancer-immunity cycle), and therapeutic sensitivity. CRNDE knockdown mitigated malignant phenotypes of LGG cells. CONCLUSIONS: Our study determined CRNDE as a novel predictor for patient prognosis, tumor immunity and therapeutic response in LGG. Assessment of CRNDE expression is a promising approach for predicting the therapeutic benefits of LGG patients.

The Active Fraction of Polyrhachis vicina Roger (AFPR) activates ERK to cause necroptosis in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Polyrhachis vicina Roger (P. vicina), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis, hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia. Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. AIM OF THE STUDY: The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. METHODS: To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology, molecular docking, qRT-PCR, western blotting, CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. RESULTS: Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. CONCLUSION: According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.

Corrigendum: Platelet abnormalities in autoimmune thyroid diseases: A systematic review and meta-analysis.

[This corrects the article DOI: 10.3389/fimmu.2022.1089469.].