Ultra-Small Copper-Based Multienzyme-Like Nanoparticles Protect Against Hepatic Ischemia-Reperfusion Injury Through Scavenging Reactive Oxygen Species in Mice.

Hepatic ischemia-reperfusion injury (IRI) is a severe complication that occurs in the process of liver transplantation, hepatectomy, and other end-stage liver disease surgery, often resulting in the failure of surgery operation and even patient death. Currently, there is no effective way to prevent hepatic IRI clinically. Here, it is reported that the ultra-small copper-based multienzyme-like nanoparticles with catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) catalytic activities significantly scavenge the surge-generated endogenous reactive oxygen species (ROS) and effectively protects hepatic IRI. Density functional theory calculations confirm that the nanoparticles efficiently scavenge ROS through their synergistic effects of the ultra-small copper SOD-like activity and manganese dioxides CAT-like activity. Furthermore, the results show that the biocompatible CMP NPs significantly protected hepatocytes from IRI in vitro and in vivo. Importantly, their therapeutic effect is much stronger than that of N-acetylcysteamine acid (NAC), an FDA-approved antioxidative drug. Finally, it is demonstrated that the protective effects of CMP NPs on hepatic IRI are related to suppressing inflammation and hepatocytic apoptosis and maintaining endothelial functions through scavenging ROS in liver tissues. The study can provide insight into the development of next-generation nanomedicines for scavenging ROS.

Dynamics of glutamine synthetase expression in hepatic ischemia-reperfusion injury: Implications for therapeutic interventions.

BACKGROUND: Hepatic ischemia-reperfusion injury (IRI) poses a great challenge in liver surgery and transplantation because of oxidative stress and inflammatory responses. The changes in glutamine synthetase (GS) expression during hepatic IRI remain unclear. AIM: To investigate the dynamic expression of GS during hepatic IRI. METHODS: Following hepatic ischemia for 1 h and reperfusion, liver tissue samples were collected at 0.5, 6, and 24 hours postreperfusion for fixation, embedding, sectioning. Hematoxylin and eosin staining and GS staining were performed. RESULTS: GS expression rapidly decreases in hepatocytes around the central vein after IRI, reaching its lowest point at 6 hours postreperfusion, and then gradually recovers. CONCLUSION: GS is highly sensitive to IRI, highlighting its potential role as an indicator of liver injury states and a target for therapeutic intervention.

Alteration of ascending colon mucosal microbiota in patients after cholecystectomy.

BACKGROUND: Cholecystectomy is a successful treatment option for gallstones, although the incidence of colorectal cancer (CRC) has notably increased in post-cholecystectomy (PC) patients. However, it remains uncertain whether the altered mucosal microbiota in the ascending colon is related. AIM: To investigate the potential correlation between gut microbiota and the surgical procedure of cholecystectomy. METHODS: In total, 30 PC patients and 28 healthy controls underwent colonoscopies to collect mucosal biopsy samples. PC patients were divided based on their clinical features. Then, 16S-rRNA gene sequencing was used to analyze the amplicon, alpha diversity, beta diversity, and composition of the bacterial communities. Additionally, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) database, sourced from the Kyoto Encyclopedia of Genes and Genomes, was used to predict the functional capabilities of the bacteria. RESULTS: PC patients were comparable with healthy controls. However, PC patients older than 60 years had a distinct composition compared to those under 60 years old. Bacteroidetes richness was considerably higher at the phylum level in PC patients. Bacteroides, Parabacteroides, and Bilophila were more abundant in the PC group than in the control group. Furthermore, PC patients exhibited greater enrichment in metabolic pathways, specifically those related to lipopolysaccharide biosynthesis and vancomycin group antibiotic production, than controls. CONCLUSION: This study indicated that the mucosal microbiota in PC patients was altered, perhaps offering new perspectives on the treatment possibilities for CRC and diarrhea following cholecystectomy.

Association of serum cystatin C level and major adverse cardiovascular events in patients with percutaneous coronary intervention.

Background: Recurrent acute myocardial infarction requiring unplanned percutaneous coronary intervention (PCI) is one of the major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS) after PCI. There is a continuing controversy about the association between serum cystatin C, a biomarker for the evaluation of renal function, and the prognosis of ACS patients following PCI. The retrospective study evaluated the association between serum cystatin C level and MACE in ACS patients after PCI. Methods: Data were retrieved for 330 patients with ACS for primary PCI in a single center. Serum cystatin C levels were measured before PCI. All patients underwent regular follow-ups after PCI, and the studied endpoint was MACE, defined as the need for a repeat revascularization in the heart. The predictive value of serum cystatin C for MACE was analyzed using univariate and multivariate analysis. Restricted cubic spline (RCS) analysis was applied to evaluate the dose-response relationship between serum cystatin C level and MACE in ACS patients following PCI. Results: After a median follow-up of 63 months (range, 1-148 months), 121 of the 330 patients experienced MACE. Compared to patients who did not have MACE, patients who had MACE showed a significant decrease in serum cystatin C levels (0.99±0.32 vs. 1.15±0.78 mg/L, P=0.03). In multivariate regression analysis, serum cystatin C level was an independent risk factor for MACE. According to the serum cystatin C level, patients were divided into 4 categories, Cox regression analysis illustrated that the second quartile of serum cystatin C level indicated an increased risk of MACE in patients with PCI for primary ACS compared to the highest quartile [Q2: adjusted hazard ratio (HR) =2.109; 95% confidence interval (CI): 1.193-3.727; P=0.01]. RCS analysis showed a significant U-shaped dose-response relationship between cystatin C level and MACE in patients with PCI for ACS (P for non-linearity =0.004). Conclusions: These results indicated an association between serum cystatin C level and post-PCI MACE in ACS patients.

Predicting clinically significant prostate cancer in elderly patients: A nomogram approach with shear wave elastography.

PURPOSE: This study was to construct a nomogram utilizing shear wave elastography and assess its efficacy in detecting clinically significant prostate cancer (csPCa). METHODS: 290 elderly people with suspected PCa who received prostate biopsy and shear wave elastography (SWE) imaging were respectively registered from April 2022 to December 2023. The elderly participants were stratified into two groups: those with csPCa and those without csPCa, which encompassed cases of clinically insignificant prostate cancer (cisPCa) and non-prostate cancer tissue, as determined by pathology findings. The LASSO algorithm, known as the least absolute shrinkage and selection operator, was utilized to identify features. Logistic regression analysis was utilized to establish models. Receiver operating characteristic (ROC) and calibration curves were utilized to evaluate the discriminatory ability of the nomogram. Bootstrap (1000 bootstrap iterations) was employed for internal validation and comparison with two models. A decision curve and a clinical impact curve were employed to assess the clinical usefulness. RESULTS: Our nomogram, which contained Emean, ΔEmean, prostate volume, prostate-specific antigen density (PSAD), and transrectal ultrasound (TRUS), showed better discrimination (AUC = 0.89; 95% CI: 0.83-0.94), compared to the clinical model without SWE parameters (p = 0.0007). Its accuracy, sensitivity and specificity were 0.83, 0.89 and 0.78, respectively. Based on the analysis of decision curve, the thresholds ranged from 5% to 90%. According to our nomogram, biopsying patients at a 20% probability threshold resulted in a 25% reduction in biopsies without missing any csPCa. The clinical impact curve demonstrated that the nomogram's predicted outcome is closer to the observed outcome when the probability threshold reaches 20% or greater. CONCLUSION: Our nomogram demonstrates efficacy in identifying elderly individuals with clinically significant prostate cancer, thereby facilitating informed clinical decision-making based on diagnostic outcomes and potential clinical benefits.

Facile Synthesis of Fe-Based Metal-Quinone Networks for Mutually Enhanced Mild Photothermal Therapy and Ferroptosis.

Mild photothermal therapy (MPTT) has emerged as a promising therapeutic modality for attenuating thermal damage to the normal tissues surrounding tumors, while the heat-induced upregulation of heat shock proteins (HSPs) greatly compromises the curative efficacy of MPTT by increasing cellular thermo-tolerance. Ferroptosis has been identified to suppress the overexpression of HSPs by the accumulation of lipid peroxides and reactive oxygen species (ROS), but is greatly restricted by overexpressed glutathione (GSH) in tumor microenvironment and undesirable ROS generation efficiency. Herein, a synergistic strategy based on the mutual enhancement of MPTT and ferroptosis is proposed for cleaving HSPs to recover tumor cell sensitivity. A facile method for fabricating a series of Fe-based metal-quinone networks (MQNs) by coordinated assembly is proposed and the representative FTP MQNs possess high photothermal conversion efficiency (69.3%). Upon 808 nm laser irradiation, FTP MQNs not only trigger effective MPTT to induce apoptosis but more significantly, potentiate Fenton reaction and marked GSH consumption to boost ferroptosis, and the reinforced ferroptosis effect in turn can alleviate the thermal resistance by declining the HSP70 defense and reducing ATP levels. This study provides a valuable rationale for constructing a large library of MQNs for achieving mutual enhancement of MPTT and ferroptosis.

The effectiveness of targeted therapy for recurrence or metastasis adenoid cystic carcinoma: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Several clinical studies have demonstrated the potential of molecular-targeted agents for the treatment of recurrent or metastatic adenoid cystic carcinoma (R/M ACC). However, there is currently no consensus regarding the efficacy of molecular-targeted agents for patients with R/M ACC. This study aimed to evaluate the therapeutic efficacy and safety of molecular-targeted agents in patients with R/M ACC and provide insights to guide clinical decision-making. MATERIALS AND METHODS: Five databases (PubMed, Embase, Cochrane, ProQuest, and Scopus) were searched based on the search strategy and selection criteria. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR), overall survival (OS), metastatic sites, and adverse events (AE). Pooled estimates were calculated using a random-effects meta-analysis. RESULTS: Finally, 28 studies, involving 849 patients, were included. The most common metastatic sites were the lungs, bones, liver, lymph nodes, and kidneys. The pooled ORR was 4.0% (95% CI, 0.7-8.8%), the pooled DCR was 80.5% (95% CI, 72.2%-87.7%). Compared with other-target drugs, multiple kinase inhibitors (MKIs) improved the ORR (pooled ORR for single-target drugs vs. MKIs: 5.9% vs. 0%). The combination of MKIs and immune checkpoint inhibitors (ICIs) had a significantly higher ORR (17.9% in the axitinib + avelumab group). The pooled median PFS and OS were 8.35 and 25.62 months, respectively. MKIs improved the median PFS compared to other-target drugs (9.43 months vs 5.06 months). In addition, the most common adverse events (AEs) were fatigue (51.6%), hypertension (44.2%), and nausea (40.0%), followed by hand-foot skin syndrome (36.8%), diarrhoea (34.4%), weight loss (34.2%), anorexia (31.8%), rash (31.7%), and headache (29.0%). CONCLUSION: The findings of this study suggest that MKIs have a better therapeutic efficacy than single-target drugs in patients with R/M ACC. Future studies are warranted to verify the synergistic role of the combination strategy of MKIs plus ICIs, given the limited number of studies on this topic conducted and published to date.

Rapid discovery of natural antioxidants in Hypericum japonicum: Dual roles of the liquid phase mobile phase as extraction and separation solvent.

Hypericum japonicum is a traditional folk medicine with various bioactivities such as hepatoprotective, antioxidant, and anti-tumorous. The antioxidant effect of H. japonicum is one of the most prominent effects due to its responsibility for many of its activities. To clarify active natural substance, the antioxidant properties of H. japonicum were preliminarily assessed by ferric reducing-antioxidant power (FRAP), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and Oxygen radical absorbance capacity (ORAC), as well as superoxide dismutase (SOD). Then, a straightforward and effective method named online liquid extraction-high performance liquid chromatography combined with ABTS antioxidant assay and mass spectrometry (OLE-HPLC-ABTS/Q-TOF-MS) was developed to swiftly and directly discover the antioxidants in H. japonicum. Using mobile phase as extraction and separation reagent, coupled with online activity analysis and compounds identification by high-resolution MS, the online system enables rapid screening of natural antioxidant bioactives from complex mixture. By using it, a total of 9 compounds including flavonoids and phenolic acids characterized by retention time, precise mass, and fragmentation ions in MS/MS spectra showed antioxidant action. Finally, the antioxidant and SOD activity of main found active compounds were validated by in vitro experiment assay and molecular docking. In summary, these results suggested that H. japonicum could be considered as a potential source of natural antioxidants, and the online integrated system might become a promising candidate for the natural antioxidants discovery in the future.

Cockroach Blaptica dubia biodegrades polystyrene plastics: Insights for superior ability, microbiome and host genes.

The report demonstrated that a member of cockroach family, Blaptica dubia (Blattodea: Blaberidae) biodegraded commercial polystyrene (PS) plastics with Mn of 20.3 kDa and Mw of 284.9 kDa. The cockroaches digested up to 46.6 % of ingested PS within 24 h. The biodegradation was confirmed by the 13C isotopic shift of the residual PS in feces versus pristine PS (Δ Î´13C of 2.28 ‰), reduction of molecular weight and formation of oxidative functional groups in the residual PS. Further tests found that B.dubia cockroaches degraded all eight high purity PS microplastics with low to ultra-high molecular weights (MW) at 0.88, 1.20, 3.92, 9.55, 62.5, 90.9, 524.0, and 1040 kDa, respectively, with superior biodegradation ability. PS depolymerization/biodegradation pattern was MW-dependent. Ingestion of PS shifted gut microbial communities and elevated abundances of plastic-degrading bacterial genes. Genomic, transcriptomic and metabolite analyses indicated that both gut microbes and cockroach host contributed to digestive enzymatic degradation. PS plastic diet promoted a highly cooperative model of gut digestive system. Weighted gene co-expression network analysis revealed different PS degradation patterns with distinct MW profiles in B. dubia. These results have provided strong evidences of plastic-degrading ability of cockroaches or Blaberidae family and new understanding of insect and their microbe mediated biodegradation of plastics.

ß-arrestin2: an emerging player and potential therapeutic target in inflammatory immune diseases.

ß-arrestin2, a pivotal protein within the arrestin family, is localized in the cytoplasm, plasma membrane and nucleus, and regulates G protein-coupled receptors (GPCRs) signaling. Recent evidence shows that ß-arrestin2 plays a dual role in regulating GPCRs by mediating desensitization and internalization, and by acting as a scaffold for the internalization, kinase activation, and the modulation of various signaling pathways, including NF-κB, MAPK, and TGF-ß pathways of non-GPCRs. Earlier studies have identified that ß-arrestin2 is essential in regulating immune cell infiltration, inflammatory factor release, and inflammatory cell proliferation. Evidently, ß-arrestin2 is integral to the pathological mechanisms of inflammatory immune diseases, such as inflammatory bowel disease, sepsis, asthma, rheumatoid arthritis, organ fibrosis, and tumors. Research on the modulation of ß-arrestin2 offers a promising strategy for the development of pharmaceuticals targeting inflammatory immune diseases. This review meticulously describes the roles of ß-arrestin2 in cells associated with inflammatory immune responses and explores its pathological relevance in various inflammatory immune diseases.

Alternative splicing variants of IiSEP3 in Isatis indigotica are involved in floral transition and flower development.

The SEPALLATA3 genes regulate several aspects of plant development. This study identified four distinct splicing isoforms of the SEPALLATA3 gene in Isatis indigotica (I. indigotica). IiSEP3-1 and IiSEP3-2 have eight exons and were named as IiSEP3-2/1. However, IiSEP3-3 and IiSEP3-4 with the missing sixth exon were labeled IiSEP3ΔK3. Furthermore, the IiSEP3-1 and IiSEP3-4 amino acids sequences lack the V90. IiSEP3 splicing variants were primarily expressed in floral organs, with petals showing the highest expression. Ectopic expression of IiSEP3-2 or IiSEP3-3 may cause early flowering and reduce the number of sepals, petals, and stamens. The ectopic expression of IiSEP3-2 resulted in cauline leaves and sepals converting to carpelloid structures. In contrast, the four floral whorls prematurely wilted, and the entire flower displayed an abortive state when IiSEP3-3 was expressed ectopically. Silencing the IiSEP3 gene of I. indigotica employing VIGS (tobacco rattle virus-mediated virus-induced gene silencing) technology using the TRV-IiSEP3-2/1 vector delayed flowering time and reduced the number of petals and stamens. Plants silenced with TRV-IiSEP3ΔK3 also exhibited similar phenotypes, including fewer sepals. The transcriptome analysis of silenced plants (TRV-IiSEP3-2/1 treatment group) indicated significant alterations in 1861 genes, with 1035 upregulated and 826 downregulated. TRV-IiSEP3ΔK3 treatment altered the expression of 2063 genes in plants, with 1289 genes upregulated and 774 genes transcription inhibited. Y2H and BIFC experiments revealed that IiSEP3-2 and IiSEP3-3 had distinct interacting proteins. Thus, we can conclude that IiSEP3-2 and IiSEP3-3 interact with different proteins, affecting floral transition and organ development in I. indigotica.

Exploring the possible therapeutic mechanism of Danzhixiaoyao pills in depression and MAFLD based on "Homotherapy for heteropathy": A network pharmacology and molecular docking.

Objective: Danzhixiaoyao pills (DXP) is a traditional Chinese medicine formula that has been effectively used in clinical practice to treat depression and metabolic associated fatty liver disease (MAFLD), but its therapeutic mechanism is not yet clear. The purpose of this study is to explore the possible mechanisms of DXP in treating depression and MAFLD using network pharmacology and molecular docking techniques based on existing literature reports. Methods: By combining TCMSP, Swiss ADME, Swiss TargetPrediction, and UniProt databases, the active ingredients and potential targets of DXP were screened and obtained. By searching for relevant disease targets through Gene Cards, OMIM, and TTD databases, intersection targets between drugs and diseases were obtained. The network of "Disease - Potential targets - Active ingredients - Traditional Chinese medicine - Prescriptions" was constructed using Cytoscape 3.9.1 software, and the PPI network was constructed using STRING 12.0 database. The core targets were obtained through topology analysis. GO function enrichment and KEGG pathway enrichment analysis were conducted based on DAVID. The above results were validated by molecular docking using PyMol 2.5 and AutoDock Tool 1.5.7 software, and their possible therapeutic mechanisms were discussed. Results: Network pharmacology analysis obtained 130 main active ingredients of drugs, 173 intersection targets between drugs and diseases, and 37 core targets. Enrichment analysis obtained 1390 GO functional enrichment results, of which 922 were related to biological process, 107 were related to cellular component, 174 were related to molecular function, and obtained 180 KEGG pathways. Molecular docking has confirmed the good binding ability between relevant components and targets, and the literature discussion has preliminarily verified the above results. Conclusion: DXP can act on targets such as TNF, AKT1, ALB, IL1B, TP53 through active ingredients such as kaempferol, quercetin, naringenin, isorhamnetin, glyuranolide, etc, and by regulating signaling pathways such as pathways in cancer, MAPK signaling pathway, lipid and atherosclerosis, to exert its effect of "homotherapy for heteropathy" on depression and MAFLD. In addition, glyuranolide showed the strongest affinity with TNF (-7.88 kcal/mol), suggesting that it may play a key role in the treatment process. The research results provide a theoretical basis for elucidating the scientific connotation and mechanism of action of traditional Chinese medicine compound DXP, and provide new directions for its clinical application.

Apolipoprotein E deficiency leads to the polarization of splenic macrophages towards M1 phenotype by increasing iron content.

Apolipoprotein E (ApoE) plays a crucial role in iron homeostasis in the body, while macrophages are the principal cells responsible for handling iron in mammals. However, it is unknown whether ApoE can affect the functional subtypes and the iron handling capacity of splenic macrophages (SM). Here, we investigated the effects of ApoE deficiency (ApoE-/-) on the polarization and iron content of SM and its potential mechanisms. ApoE-/- was found to induce a significant increase in the expressions of M1 marker genes CD86, IL-1ß, IL-6, IL-12, TNF-α and iNOS and a reduction in M2 marker genes CD206, Arg-1, IL-10 and Ym-1 in SM of mice aged 28 weeks, Meanwhile, ApoE-/- caused a significant increase in iron content and expression of ferritin, transferrin receptor 1 (TfR1), iron regulatory protein 1 (IRP1) and heme oxygenase-1 (HO-1) and a reduction in ferroportin1 (Fpn1) in spleen and/or SM of mice aged 28 weeks. It was concluded that ApoE-/- can increase iron content through increased iron uptake mediated by TfR/ IRPs and decreased iron release mediated by Fpn1, leading to polarization of the SM to M1 phenotype.

Fatty links between multisystem proteinopathy and small VCP-interacting protein.

Multisystem proteinopathy (MSP) is a rare, dominantly inherited disorder that includes a cluster of diseases, including frontotemporal dementia, inclusion body myopathy, and Paget's disease of bone. MSP is caused by mutations in the gene encoding valosin-containing protein (VCP). Patients with the same mutation, even within the same family, can present with a different combination of any or all of the above diseases, along with amyotrophic lateral sclerosis (ALS). The pleiotropic effects may be linked to the greater than 50 VCP co-factors that direct VCP's many roles in the cell. Small VCP-interacting protein (SVIP) is a small protein that directs VCP to autophagosomes and lysosomes. We found that SVIP directs VCP localization to lysosomes in an acylation-dependent manner. We demonstrate that SVIP is myristoylated at Glycine 2 and palmitoylated at Cysteines 4 and 7. Acylation of SVIP is required to mediate cell death in the presence of the MSP-associated VCP variant (R155H-VCP), whereas blocking SVIP myristoylation prevents cytotoxicity. Therefore, SVIP acylation may present a novel target in MSP.

[Efficiency of different large language models in China in response to consultations about PCa-related perioperative nursing and health education].

OBJECTIVE: To evaluate the efficiency of the four domestic language models, ERNIE Bot, ChatGLM2, Spark Desk and Qwen-14B-Chat, all with a massive user base and significant social attention, in response to consultations about PCa-related perioperative nursing and health education. METHODS: We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases, and inputted the questions into each of the four language models for simulation consultation. Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy, comprehensiveness, understandability, humanistic care, and case analysis. We evaluated and compared the performance of the four models using visualization tools and statistical analyses. RESULTS: All the models generated high-quality texts with no misleading information and exhibited satisfactory performance. Qwen-14B-Chat scored the highest in all aspects and showed relatively stable outputs in multiple tests compared with ChatGLM2. Spark Desk performed well in terms of understandability but lacked comprehensiveness and humanistic care. Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis. The overall performance of ERNIE Bot was slightly inferior. All things considered, Qwen-14B-Chat was superior to the other three models in consultations about PCa-related perioperative nursing and health education. CONCLUSION: In PCa-related perioperative nursing, large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support, so as to improve the patient compliance and the quality of clinical treatment and nursing.

Multifunctional single-component photosensitizers as metal-free ferroptosis inducers for enhanced photodynamic immunotherapy.

Immunotherapy can enhance primary tumor efficacy, restrict distant growth, and combat lung metastasis. Unfortunately, it remains challenging to effectively activate the immune response. Here, tertiary butyl, methoxy, and triphenylamine (TPA) were utilized as electron donors to develop multifunctional photosensitizers (PSs). CNTPA-TPA, featuring TPA as the donor (D) and cyano as the acceptor (A), excelled in reactive oxygen species (ROS) generation due to its smaller singlet-triplet energy gap (ΔES-T) and larger spin-orbit coupling constant (SOC). Additionally, cyano groups reacted with glutamate (Glu) and glutathione (GSH), reducing intracellular GSH levels. This not only enhanced PDT efficacy but also triggered redox dyshomeostasis-mediated ferroptosis. The positive effects of photodynamic therapy (PDT) and ferroptosis promoted immunogenic cell death (ICD) and immune activation. By further combining anti-programmed cell death protein ligand-1 (anti-PD-L1) antibody, the powerful treatments of ferroptosis-assisted photodynamic immunotherapy significantly eradicated the primary tumors, inhibited the growth of distant tumors, and suppressed lung metastasis. In this study, a three-pronged approach was realized by single-component CNTPA-TPA, which simultaneously served as metal-free ferroptosis inducers, type-I photosensitizers, and immunologic adjuvants for near-infrared fluorescence imaging (NIR FLI)-guided multimodal phototheranostics of tumor. STATEMENT OF SIGNIFICANCE: (1) CNTPA-TPA shared the smallest singlet-triplet energy gap and the largest spin-orbit coupling constant, which boosted intersystem crossing for efficient type-I photodynamic therapy (PDT); (2) Special reactions between cyano groups with glutamate and glutathione in mild conditions restricted the biosynthesis of intracellular GSH. GSH-depletion efficiently induced glutathione peroxidase 4 inactivation and lipid peroxide, resulting in ferroptosis of tumor cells; (3) The combination treatments of ferroptosis-assisted photodynamic immunotherapy induced by single-component CNTPA-TPA with the participation of anti-PD-L1 antibody resulted in increased T-cell infiltration and profound suppression of both primary and distant tumor growth, as well as lung metastasis.

The Effects of Pulmonary Artery Catheter on the Short-Term Outcomes of Patients Undergoing Off-Pump Coronary Artery Bypass Grafting: A Single-Center Retrospective Study.

Background: Pulmonary artery catheters (PAC) are widely used in patients undergoing off-pump coronary artery bypass (OPCAB) grafting surgery. However, primary data suggested that the benefits of PAC in surgical settings were limited. Therefore, the present study sought to estimate the effects of PAC on the short-term outcomes of patients undergoing OPCAB surgery. Methods: The characteristics, intraoperative data, and postoperative outcomes of consecutive patients undergoing primary, isolated OPCAB surgery from November 2020 to December 2021 were retrospectively extracted. Patients were divided into two groups (PAC and no-PAC) based on PAC insertion status. Data were analyzed with a 1:1 nearest-neighbor propensity score matched-pair in PAC and no-PAC groups. Results: Of the 1004 Chinese patients who underwent primary, isolated OPCAB surgery, 506 (50.39%) had PAC. Propensity score matching yielded 397 evenly balanced pairs. Compared with the no-PAC group (only implanted a central venous catheter), PAC utilization was not associated with improved in-hospital mortality in the entire or matched cohort. Still, the matched cohort showed that PAC utilization increased epinephrine usage and hospital costs. Conclusions: The current study demonstrated no apparent benefit or harm for PAC utilization in OPCAB surgical patients. In addition, PAC utilization was more expensive.

Distribution, risk evaluation, and source allocation of cesium and strontium in surface soil in a mining city.

Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.

Sulfur-Vacancy-Engineered Two-Dimensional Cu@SnS2-x Nanosheets Constructed via Heterovalent Substitution for High-Efficiency Piezocatalytic Tumor Therapy.

Ultrasound (US)-mediated piezocatalytic tumor therapy has attracted much attention due to its notable tissue-penetration capabilities, noninvasiveness, and low oxygen dependency. Nevertheless, the efficiency of piezocatalytic therapy is limited due to an inadequate piezoelectric response, low separation of electron-hole (e--h+) pairs, and complex tumor microenvironment (TME). Herein, an ultrathin two-dimensional (2D) sulfur-vacancy-engineered (Sv-engineered) Cu@SnS2-x nanosheet (NS) with an enhanced piezoelectric effect was constructed via the heterovalent substitution strategy of Sn4+ by Cu2+. The introduction of Cu2+ ion not only causes changes in the crystal structure to increase polarization but also generates rich Sv to decrease band gap from 2.16 to 1.62 eV and inhibit e--h+ pairs recombination, collectively leading to the highly efficient generation of reactive oxygen species under US irradiation. Moreover, Cu@SnS2-x shows US-enhanced TME-responsive Fenton-like catalytic activity and glutathione depletion ability, further aggravating the oxidative stress. Both in vitro and in vivo results prove that the Sv-engineered Cu@SnS2-x NSs can significantly kill tumor cells and achieve high-efficiency piezocatalytic tumor therapy in a biocompatible manner. Overall, this study provides a new avenue for sonocatalytic therapy and broadens the application of 2D piezoelectric materials.