Impact of non-emergency surgical timing on postoperative recovery quality in mild or asymptomatic SARS-CoV-2 infected patients: a grouped cohort study.

OBJECTIVE: To explore the relationship between the timing of non-emergency surgery in mild or asymptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infected individuals and the quality of postoperative recovery from the time of confirmed infection to the day of surgery. METHODS: We retrospectively reviewed the medical records of 300 cases of mild or asymptomatic SARS-CoV-2 infected patients undergoing elective general anaesthesia surgery at Yijishan Hospital between January 9, 2023, and February 17, 2023. Based on the time from confirmed SARS-CoV-2 infection to the day of surgery, patients were divided into four groups: ≤2 weeks (Group A), 2-4 weeks (Group B), 4-6 weeks (Group C), and 6-8 weeks (Group D). The primary outcome measures included the Quality of Recovery-15 (QoR-15) scale scores at 3 days, 3 months, and 6 months postoperatively. Secondary outcome measures included postoperative mortality, ICU admission, pulmonary complications, postoperative length of hospital stay, extubation time, and time to leave the PACU. RESULTS: Concerning the primary outcome measures, the QoR-15 scores at 3 days postoperatively in Group A were significantly lower compared to the other three groups (P < 0.05), while there were no statistically significant differences among the other three groups (P > 0.05). The QoR-15 scores at 3 and 6 months postoperatively showed no statistically significant differences among the four groups (P > 0.05). In terms of secondary outcome measures, Group A had a significantly prolonged hospital stay compared to the other three groups (P < 0.05), while other outcome measures showed no statistically significant differences (P > 0.05). CONCLUSION: The timing of surgery in mild or asymptomatic SARS-CoV-2 infected patients does not affect long-term recovery quality but does impact short-term recovery quality, especially for elective general anaesthesia surgeries within 2 weeks of confirmed infection. Therefore, it is recommended to wait for a surgical timing of at least greater than 2 weeks to improve short-term recovery quality and enhance patient prognosis.

Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report.

Castleman disease (CD) is a relatively rare lymphoproliferative disorder. Lesions predominantly originate on the chest and neck and rarely occur on the abdomen. A 34-year-old female presented to our hospital with an unexplained 10-year history of anemia. A pathological diagnosis of plasma cell-type CD was established. One cycle of chemotherapy (thalidomide, cyclophosphamide, and prednisolone) improved her anemia significantly. Prompt etiological diagnosis and early intervention are essential to address systemic manifestations in patients with CD, and it is crucial to consider CD as a differential diagnosis when intra-abdominal masses are detected.

Effect of phenylephrine versus ephedrine on the incidence of postoperative delirium in olderly adults undergoing knee arthroplasty under general anesthesia: a single-center trial.

In addition to stabilizing blood pressure (BP), ephedrine and phenylephrine have distinct effects on regional cerebral oxygen saturation (rSO2). However, whether its effect on rSO2 affects the occurrence of postoperative delirium (POD) remains unclear. Therefore, the aim of this study is to compare the effects of ephedrine and phenylephrine for BP maintenance on the incidence of POD in olderly adults who underwent knee arthroplasty under general anesthesia. One hundred twenty patients who were between 60 and 90 years old and underwent knee arthroplasty were included in this study. The patients were randomly divided into two groups: the ephedrine group and the phenylephrine group. After anesthesia induction, ephedrine and phenylephrine were continuously infused to maintain the intraoperative mean arterial pressure within the normal range (baseline mean arterial pressure ± 20%). The primary outcome measures included the incidence of POD within 1-3 days after surgery. The incidence of POD on the first day after surgery was lower in the ephedrine group than in the phenylephrine group (33% vs. 7%, P < 0.001). However, there was no significant difference in the incidence of POD between the two groups on the second and third postoperative days. Compared with the phenylephrine group, the ephedrine group experienced significantly greater cardiac output (CO) and rSO2 (P < 0.05).Clinical Trials Registry: ChiCTR2200064849, principal investigator: Changjian Zheng.

Pathogenic Autoimmunity in Atherosclerosis Evolves from HSP60-Reactive CD4 + T Cells.

Clinical evidence suggests anti-Hsp60 antibodies could contribute to atherosclerosis (AS) development, with unclear mechanisms. This study aims to explore the role of anti-HSP60-mediated autoimmunity in AS progression. HSP60-MHC tetramers were used to characterize HSP60-specific CD4 + T cells and assess TCR responses in mice. These cells were transplanted into AS mice to examine immune cell differentiation and infiltration in plaques and blood. Mice were injected with recombinant HSP60 or anti-HSP60 sera to evaluate effects on plaque progression and macrophage activity. Experiments with muMT-/-Apoe-/- mice examined humoral immunity's role in this autoimmunity. HSP60-reactive CD4 + T cells in AS mice differentiated into follicular helper cells, not Th1/Th17. Anti-HSP60 treatments increased macrophage infiltration and M1 polarization, indicating an anti-HSP60-driven inflammatory progression, dependent on humoral immunity. Anti-HSP60 influences macrophage infiltration, polarization, and plaque formation via humoral immunity, shedding light on its potential role in AS progression.

Effect of CHST11, a novel biomarker, on the biological functionalities of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor, and the role of carbohydrate sulfotransferase 11 (CHST11) in this cancer remains unclear. Here, by using bioinformatics methods, we comprehensively analyzed the relationship between CHST11 and clinical significance, immune infiltration, functional enrichment, m6A methylation, and protein-protein interaction networks. We found that CHST11 expression was significantly higher in ccRCC samples than in normal tissues. Additionally, CHST11 levels correlated with the clinicopathological features of ccRCC patients and functioned as a prognostic factor for patient survival. Functional analysis revealed the involvement of CHST11 in metabolic pathways. Immune infiltration and m6A methylation analysis suggested the association of CHST11 with immune cell abundance in the tumor microenvironment and specific methylation patterns in ccRCC. The in vitro analysis of the clinical samples and ccRCC cell lines demonstrated that the overexpression of CHST11 promotes ccRCC cell proliferation, migration, and invasion, while its suppression has the opposite effect. Thus, CHST11 may play a remarkable role in the occurrence and progression of ccRCC. Functionally, CHST11 promotes the aggressiveness of ccRCC cells. These findings provide insights into the role of CHST11 in ccRCC progression.Registry and the Registration No. of the study/trial: No. 2021K034.

Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathy.

Diabetic cystopathy (DCP) is a prevalent etiology of bladder dysfunction in individuals with longstanding diabetes, frequently leading to bladder interstitial fibrosis. Research investigating the initial pathological alterations of DCP is notably scarce. To comprehend the development of fibrosis and find effective biomarkers for its diagnosis, we prepared streptozotocin-induced long-term diabetic SD rats exhibiting a type 1 diabetes phenotype and bladder fibrosis in histology detection. After observing myofibroblast differentiation from rats' primary bladder fibroblasts with immunofluorescence, we isolated fibroblasts derived exosomes and performed exosomal miRNA sequencing. The co-differentially expressed miRNAs (DEMis) (miR-16-5p and let-7e-5p) were screened through a joint analysis of diabetic rats and long-term patients' plasma data (GES97123) downloaded from the GEO database. Then two co-DEMis were validated by quantitative PCR on exosomes derived from diabetic rats' plasma. Following with a series of analysis, including target mRNAs and transcription factors (TFs) prediction, hubgenes identification, protein-protein interaction (PPI) network construction and gene enrichment analysis, a miRNA-mediated genetic regulatory network consisting of two miRNAs, nine TFs, and thirty target mRNAs were identified in relation to fibrotic processes. Thus, circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of DCP, and the crucial genes in regulatory network might hold immense significance in studying the pathogenesis and molecular mechanisms of fibrosis, which deserves further exploration.

Divide and Conquer: Improving Multi-Camera 3D Perception With 2D Semantic-Depth Priors and Input-Dependent Queries.

3D perception tasks, such as 3D object detection and Bird's-Eye-View (BEV) segmentation using multi-camera images, have drawn significant attention recently. Despite the fact that accurately estimating both semantic and 3D scene layouts are crucial for this task, existing techniques often neglect the synergistic effects of semantic and depth cues, leading to the occurrence of classification and position estimation errors. Additionally, the input-independent nature of initial queries also limits the learning capacity of Transformer-based models. To tackle these challenges, we propose an input-aware Transformer framework that leverages Semantics and Depth as priors (named SDTR). Our approach involves the use of an S-D Encoder that explicitly models semantic and depth priors, thereby disentangling the learning process of object categorization and position estimation. Moreover, we introduce a Prior-guided Query Builder that incorporates the semantic prior into the initial queries of the Transformer, resulting in more effective input-aware queries. Extensive experiments on the nuScenes and Lyft benchmarks demonstrate the state-of-the-art performance of our method in both 3D object detection and BEV segmentation tasks.

A novel AllGlo probe-quantitative PCR method for detecting single nucleotide polymorphism in CYP2C19 to evaluate the antiplatelet activity of clopidogrel.

CYP2C19 gene has multiple single nucleotide polymorphism (SNP), which is the major determinant for clopidogrel treatment responses. Therefore, CYP2C19 SNP detection is essential for predicting clopidogrel efficacy. Currently, there is still no quick and effective method for routine detection of common CYP2C19 SNPs in clinical laboratories, which is critically needed prior to clopidogrel treatment. AllGlo™ based quantitative PCR was used to develop a novel genotyping method for CYP2C19 SNP detection, termed CyPAllGlo. The performance of CyPAllGlo was compared with that of the commonly used fluorescence in situ hybridization (FISH) method, and the data was verified by DNA sequencing. CyPallGlo was used to identify CYP2C19 polymorphisms in 363 patients with coronary heart disease. The univariate analysis was used to access the antiplatelet efficacy of clopidogrel in patients. The associations between CYP2C19 polymorphisms and clopidogrel efficacy were analyzed. Using CyPAllGlo to detect CYP2C19*2 and CYP2C19*3 alleles was highly specific and fast. The detection limit was approximately 0.07 µg/µl and 0.7 µg/µl for CYP2C19*2 and CYP2C19*3, respectively. The consistency between FISH and CyPAllGlo were 98.07% for CYP2C19*2 and 99.17% for CYP2C19*3. DNA sequencing showed that the accuracy of CyPAllGlo was 100%. The analysis time for the whole CyPAllGlo procedure was approximately 60 min. Univariate analysis showed that the anticoagulation efficacy of clopidogrel was related to patient age, CYP2C19 genotype, metabolic phenotype, and LDL level. The logistic regression analysis showed that the genotype of CYP2C19 and metabolic phenotype was the two risk factors for clopidogrel antiplatelet ineffectiveness. This novel CyPAllGlo is a rapid and accurate method for detection of CYP2C19 SNP. The specificity and consistency of CyPAllGlo are comparable with that of widely used DNA sequencing. These findings provide valuable rapid method for predicting clopidogrel efficacy, which can be quickly translated to improve personalized precision medicine for coronary heart disease treatment.

T-2 Toxin-Mediated ß-Arrestin-1 O-GlcNAcylation Exacerbates Glomerular Podocyte Injury via Regulating Histone Acetylation.

T-2 toxin causes renal dysfunction with proteinuria and glomerular podocyte damage. This work explores the role of metabolic disorder/reprogramming-mediated epigenetic modification in the progression of T-2 toxin-stimulated podocyte injury. A metabolomics experiment is performed to assess metabolic responses to T-2 toxin infection in human podocytes. Roles of protein O-linked-N-acetylglucosaminylation (O-GlcNAcylation) in regulating T-2 toxin-stimulated podocyte injury in mouse and podocyte models are assessed. O-GlcNAc target proteins are recognized by mass spectrometry and co-immunoprecipitation experiments. Moreover, histone acetylation and autophagy levels are measured. T-2 toxin infection upregulates glucose transporter type 1 (GLUT1) expression and enhances hexosamine biosynthetic pathway in glomerular podocytes, resulting in a significant increase in ß-arrestin-1 O-GlcNAcylation. Decreasing ß-arrestin-1 or O-GlcNAc transferase (OGT) effectively prevents T-2 toxin-induced renal dysfunction and podocyte injury. Mechanistically, O-GlcNAcylation of ß-arrestin-1 stabilizes ß-arrestin-1 to activate the mammalian target of rapamycin (mTOR) pathway as well as to inhibit autophagy during podocyte injury by promoting H4K16 acetylation. To sum up, OGT-mediated ß-arrestin-1 O-GlcNAcylation is a vital regulator in the development of T-2 toxin-stimulated podocyte injury via activating the mTOR pathway to suppress autophagy. Targeting ß-arrestin-1 or OGT can be a potential therapy for T-2 toxin infection-associated glomerular injury, especially podocyte injury.

Impact of multimodal analgesia on postoperative anxiety and depression following total knee arthroplasty.

BACKGROUND: Postoperative pain after total knee arthroplasty (TKA) can cause negative emotions, such as anxiety and depression, which can severely affect a patient's long-term quality of life. OBJECTIVE: This study aimed to investigate the impact of multimodal analgesia (MMA) on postoperative anxiety and depression following total knee arthroplasty. METHODS: This study included 161 patients who underwent TKA from October 2020 to October 2022 in the First Affiliated Hospital of Wannan Medical College, including 79 cases in the control group and 82 cases in the multimodal analgesia group (MMA). The MMA group were administered acetaminophen 0.5 g/d orally 3 days before the surgery, and an ultrasound-guided fascia iliac compartment block (FICB) with 0.25% ropivacaine 30 ml in the inguinal region ipsilateral to the surgery was performed 1 h before surgery. After the surgery, 100 ml solution includes 100 mg ropivacaine, 2.5 mg morphine, and 0.25 mg epinephrine for intra-articular and periarticular injection. Postoperative conventional intravenous analgesia was used in the control group, including 100 mg ropivacaine, 2.5 mg morphine, and 0.25 mg epinephrine for intra-articular and periarticular injection. Patients were scored for pain, anxiety, and depression in the ward at 3 and 7 days postoperatively, and postoperative patients were scored using telephone callbacks at 3 months postoperatively. RESULTS: It was found that the visual analog scale (VAS) scores for pain at rest at 3 days, 7 days, and 3 months postoperatively were significantly lower in the MMA group than in the control group (P < 0.05). The scores for pain with movement were significantly lower in the MMA group than in the control group at 3 days and 7 days postoperatively (P < 0.01), but they were similar at 3 months postoperatively. Compared to the control group, the MMA group had significantly higher American Knee Society scores (AKS) at 3 days, 7 days, and 3 months postoperatively (P < 0.05). Compared to the control group, the MMA group had significantly higher Lower Extremity Functional Scale and Hospital Anxiety and Depression Scale scores (HADS) (P < 0.05) at 3 days and 7 days postoperatively; compared to the control group, the MMA group had a significantly shorter hospital stay (P < 0.01). CONCLUSION: Multimodal analgesia can alleviate postoperative anxiety and depression in the short term, reduce perioperative pain, improve postoperative recovery, and shorten the length of hospital stay.

CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review.

In the human immunodeficiency virus (HIV)-infected population, especially HIV with concomitant tuberculosis (TB) or Hodgkin's lymphoma (HL), numerous risk factors have been reported in recent years. Among them, the decreased CD4+ T cell count was recognized as the common risk factor. We report a case of a patient with HIV and TB and HL co-occurrence, in which patient's CD4+ T cell count was inconsistent with disease. A 58-year-old male presented with fever and shortness of breath that persisted for 2 months. The patient had a 4-year history of HIV infection and underwent antiretroviral therapy (ART) effectively. After blood test, computed tomography, bone biopsy, and lymphoma biopsy, the patient was diagnosed with skeletal TB and HL, underwent TB treatment and received ART, and underwent four cycles of chemotherapy. CD4+ T cell count was not decreased before diagnosed with TB/HL and increased in this case after the fourth cycle of chemotherapy. We collected and analyzed CD4+ T cell counts in our case and reviewed relevant literature. It is suggested that CD4+ T cell count may be insufficient to predict the risk of HIV-related disease, especially lymphoproliferative disorders.

A novel necroptosis-related long noncoding RNA model for predicting clinical features, immune characteristics, and therapeutic response in clear cell renal cell carcinoma.

Background: Necroptosis is an immune-related cell death pathway involved in the regulation of the tumor microenvironment (TME). Here, we aimed to explore the role of necroptosis in clear cell renal cell carcinoma (ccRCC) and construct a necroptosis-related lncRNA (NRL) model to assess its potential association with clinical characteristics and immune status. Methods: Gene expression profiles and clinical data for ccRCC patients were obtained from the Cancer Genome Atlas (TCGA). Pearson's correlation, univariate Cox, and least absolute shrinkage and selection operator analyses were used to develop an NRL model. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve analyses were used to determine the prognostic value of the NRL model. The clinical information was used to assess the diagnostic value of the NRL model. The TME, immune function, immune cell infiltration, and immune checkpoints associated with the NRL model risk score were studied using the ESTIMATE, GSEA, ssGSEA, and CIBERSORT algorithms. The immunophenoscore (IPS) and half-maximal inhibitory concentration (IC50) were used to compare the efficacies of immunotherapy and chemotherapy based on the NRL model. Finally, in vitro assays were performed to confirm the biological roles of NRLs. Results: A total of 18 necroptosis-related genes and 285 NRLs in ccRCC were identified. A four-NRL model was constructed and showed good performance in the diagnosis and prognosis of ccRCC patients. The ESTIMATE scores, tumor mutation burden, and tumor stemness indices were significantly correlated with NRL model risk score. Immune functions such as chemokine receptors and immune receptor activity showed differences between different risk groups. The infiltration of immunosuppressive cells such as Tregs was higher in high-risk patients than in low-risk patients. High-risk patients were more sensitive to immunotherapy and some chemotherapy drugs, such as sunitinib and temsirolimus. Finally, the expression of NRLs included in the model was verified, and knocking down these NRLs in tumor cells affected cell proliferation, migration, and invasion. Conclusion: Necroptosis plays an important role in the progression of ccRCC. The NRL model we constructed can be used to predict the clinical characteristics and immune features of ccRCC patients.

Surrounding-aware representation prediction in Birds-Eye-View using transformers.

Birds-Eye-View (BEV) maps provide an accurate representation of sensory cues present in the surroundings, including dynamic and static elements. Generating a semantic representation of BEV maps can be a challenging task since it relies on object detection and image segmentation. Recent studies have developed Convolutional Neural networks (CNNs) to tackle the underlying challenge. However, current CNN-based models encounter a bottleneck in perceiving subtle nuances of information due to their limited capacity, which constrains the efficiency and accuracy of representation prediction, especially for multi-scale and multi-class elements. To address this issue, we propose novel neural networks for BEV semantic representation prediction that are built upon Transformers without convolution layers in a significantly different way from existing pure CNNs and hybrid architectures that merge CNNs and Transformers. Given a sequence of image frames as input, the proposed neural networks can directly output the BEV maps with per-class probabilities in end-to-end forecasting. The core innovations of the current study contain (1) a new pixel generation method powered by Transformers, (2) a novel algorithm for image-to-BEV transformation, and (3) a novel network for image feature extraction using attention mechanisms. We evaluate the proposed Models performance on two challenging benchmarks, the NuScenes dataset and the Argoverse 3D dataset, and compare it with state-of-the-art methods. Results show that the proposed model outperforms CNNs, achieving a relative improvement of 2.4 and 5.2% on the NuScenes and Argoverse 3D datasets, respectively.

Causal Effects between Gut Microbiome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Two-Sample Mendelian Randomization Study.

Background: Evidence from previous studies have implicated an important association between gut microbiota (GM) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), but whether there is a definite causal relationship between GM and ME/CFS has not been elucidated. Method: This study obtained instrumental variables of 211 GM taxa from the Genome Wide Association Study (GWAS), and mendelian randomization (MR) study was carried out to assess the effect of gut microbiota on ME/CFS risk from UK Biobank GWAS (2076 ME/CFS cases and 460,857 controls). Inverse variance weighted (IVW) was the primary method to analyze causality in this study, and a series of sensitivity analyses was performed to validate the robustness of the results. Results: The inverse variance weighted (IVW) method indicated that genus Paraprevotella (OR:1.001, 95%CI:1.000-1.003, value of p < 0.05) and Ruminococca- ceae_UCG_014 (OR 1.003, 95% CI 1.000 to 1.005, value of p < 0.05) were positively associated with ME/CFS risk. Results from the weighted median method supported genus Paraprevotella (OR 1.003, 95% CI 1.000 to 1.005, value of p < 0.05) as a risk factor for ME/CFS. Conclusion: This study reveals a causal relationship between genus paraprevotella, genus Ruminococcaceae_UCG_014 and ME/CFS, and our findings provide novel insights for further elucidating the developmental mechanisms mediated by the gut microbiota of ME/CFS.

Constructing and Validating a Dynamic Nomogram to Predict Response to Bariatric Surgery: A Multicenter Retrospective Study.

PURPOSE: Suboptimal response is one of the major problems for bariatric surgery, and constructing an individualized model for predicting outcomes of bariatric surgery is essential. Thus, the aim of this study is to develop a nomogram to predict the response to bariatric surgery. MATERIALS AND METHODS: 509 patients who underwent bariatric surgery between 2019 to 2020 from 6 centers were retrieved and assessed. Multiple Imputation was used to replace missing data. Patients with %TWL ≥ 20% 1 year after bariatric surgery were classified as patients with optimal response, while the others were patients with suboptimal response. A web-based nomogram was constructed and validated. ROC curve and calibration curve were used to determine the predictive ability of our model. RESULTS: 56 (11.0%) patients were classified as patients with suboptimal response, and they showed advanced age, lower pre-operative BMI, smaller waist circumference, higher fasting glucose, higher HbA1c and lower fasting insulin compared to patients with optimal response. A forward likelihood ratio logistic regression analysis indicated that age (OR = 0.943, 95% CI: 0.915-0.971, p < 0.001), pre-operative BMI (OR = 1.109, 95% CI: 1.002-1.228, p = 0.046) and waist circumference (OR = 1.043, 95% CI: 1.000-1.088, p = 0.048) were essential factors contributing to the response to bariatric surgery. Lastly, a web-based nomogram was constructed to predict the response to bariatric surgery and demonstrated an AUC of 0.829 and 0.798 upon internal and external validation. CONCLUSION: Age, BMI and fasting glucose were proved to be essential factors influencing the response to bariatric surgery. The nomogram constructed in this study demonstrated good adaptivity.

BNIP3 overexpression may promote myeloma cell apoptosis by enhancing sensitivity to bortezomib via the p38 MAPK pathway.

BACKGROUND: BCL2-interacting protein 3 (BNIP3) expression varies among cancers, and its role in myeloma cells remains unknown. We investigated the role of BNIP3 overexpression in myeloma cells, and particularly its effects on apoptosis and mitochondria. METHODS: A BNIP3-overexpressing plasmid was transfected into the MM.1S and RPMI8226 myeloma cell lines. Transfected cell apoptosis rate and mitochondrial function were determined via flow cytometry and western blotting. We verified the signaling pathway underlying myeloma cell sensitivity to bortezomib (BTZ). RESULTS: Cell lines carrying the BNIP3-overexpressing plasmid exhibited higher rates of apoptosis and expression of Bax and Cleaved caspase 3 protein than the vector group, and less Bcl-2 protein expression than the control cells. Relative to the vector group, BNIP3-overexpressing strains contained more reactive oxygen species (ROS) and exhibited mitochondrial membrane potential (MMP) and dynamin-related protein 1 (Drp1) upregulation and mitofusin-1 (Mfn1) downregulation. BTZ supplementation increased BNIP3 expression. Relative to the BNIP3-OE group, the BNIP3-OE BTZ-treated group exhibited upregulated Bax and Cleaved caspase 3 protein expression, downregulated Bcl-2 protein expression, higher apoptosis rates, ROS levels, MMP, and Drp1 expression, and lower Mfn1 expression. BTZ treatment induced p38 MAPK (mitogen-activated protein kinase) signaling pathway activation in BNIP3-OE cells. Upon adding N-acetylcysteine (NAC) and the p38 MAPK inhibitor SB203580, the affected index levels returned to the baseline. CONCLUSIONS: BNIP3 overexpression induced apoptosis in myeloma cells and increased myeloma cell sensitivity to BTZ. These effects may be mediated by the ROS/p38 MAPK signaling pathway.

Development and validation of a novel 5 cuproptosis-related long noncoding RNA signature to predict diagnosis, prognosis, and drug therapy in clear cell renal cell carcinoma.

Background: Cuproptosis has been reported as a new form of cell death. However, its potential mechanism of action in clear cell renal cell carcinoma (ccRCC) remains unclear. Therefore, we systematically clarified the role of cuproptosis in ccRCC and aimed to develop a novel signature of cuproptosis-related long noncoding RNAs (lncRNA) (CRLs) to assess the clinical characteristics of ccRCC patients. Methods: Gene expression, copy number variation, gene mutation, and clinical data for ccRCC were obtained from The Cancer Genome Atlas (TCGA). CRL signature was constructed with least absolute shrinkage and selection operator (LASSO) regression analysis. The clinical diagnostic value of the signature was verified by clinical data. The prognostic value of the signature was detected by Kaplan-Meier analysis and receiver operating characteristic (ROC) curve. The prognostic value of the nomogram was evaluated by calibration curves, ROC curves, and decision curve analysis (DCA). Gene set enrichment analysis (GSEA), single sample GSEA (ssGSEA) and cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm were used to analyze the differences of immune function and immune cell infiltration among different risk groups. Prediction of clinical treatment differences in populations with different risks and susceptibilities was completed with R package (The R Foundation of Statistical Computing). Verification of key lncRNA expression was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The cuproptosis-related genes were extensively dysregulated in ccRCC. A total of 153 differentially expressed prognostic CRLs were identified in ccRCC. Furthermore, a 5-lncRNA signature (AC015912.3, AC026401.3, AC103706.1, AC134312.5, and EMX2OS) were obtained that showed good performance in the diagnosis and prognosis of ccRCC. The nomogram could more accurately predict overall survival (OS). Immune functions such as T-cell and B-cell receptor signaling pathways showed differences between different risk groups. Clinical treatment value analysis showed that the signature may be able to effectively guide immunotherapy and target therapy. In addition, qRT-PCR results showed significant differences in the expression of key lncRNAs in ccRCC. Conclusions: Cuproptosis plays an important role in the progression of ccRCC. The 5-CRL signature can guide the prediction of clinical characteristics and tumor immune microenvironment of ccRCC patients.

Stimuli-Responsive Double Single-Atom Catalysts for Parallel Catalytic Therapy.

Tumor microenvironment (TME)-induced nanocatalytic therapy is a trending strategy for tumor-targeting therapy, but the low catalytic efficiency remains to limit its therapeutic effect. The single-atom catalysts (SACs) appear as a novel type of nanozymes that possesses incredible catalytic activity. Here, we developed PEGylated manganese/iron-based SACs (Mn/Fe PSACs) by coordinating single-atom Mn/Fe to nitrogen atoms in hollow zeolitic imidazolate frameworks (ZIFs). Mn/Fe PSACs catalyze cellular hydrogen peroxide (H2O2) converting to hydroxyl radical (•OH) through a Fenton-like reaction; it also enhances the decomposition of H2O2 to O2 that continuously converts to cytotoxic superoxide ion (•O2-) via oxidase-like activity. Mn/Fe PSACs can reduce the depletion of reactive oxygen species (ROS) by consuming glutathione (GSH). Here, we demonstrated the Mn/Fe PSACs-mediated synergistic antitumor efficacy among in vitro and in vivo experiments. This study proposes new promising single-atom nanozymes with highly efficient biocatalytic sites and synergistic therapeutic effects, which will give birth to abundant inspirations in ROS-related biological applications in broad biomedical fields.