Functional connectivity compensation in Parkinson's disease with freezing of gait.

Freezing of gait (FOG) is a disabling motor symptom prevalent in patients with Parkinson's disease (PD); however, its pathophysiological mechanisms are poorly understood. This study aimed to investigate whole-brain functional connectivity (FC) pattern alterations in PD patients with FOG. A total of 18 PD patients, 10 with FOG (PD-FOG) and 8 without FOG (PD-nFOG), and 10 healthy controls were enrolled. High-resolution 3D T1-weighted and resting-state functional MRI (rs-fMRI) data were obtained from all participants. The groups' internetwork connectivity differences were explored with rs-fMRI FC using seed-based analysis and graph theory. Multiple linear regression analysis estimated the relationship between FC changes and clinical measurements. Rs-fMRI analysis demonstrated alterations in FC in various brain regions between the three groups. Freezing of Gait Questionnaire severity was correlated with decreased brain functional connection between Vermis12 and the left temporal occipital fusiform cortex (r = -0.82, P < .001). Graph theory topological metrics indicated a decreased clustering coefficient in the right superior temporal gyrus in the PD-nFOG group. PD-FOG patients exhibited a compensatory increase in connectivity between the left inferior frontal gyrus language network and the postcentral gyrus compared to PD-nFOG patients. Further, the decreased connection between Vermis 12 and the left temporal occipital fusiform cortex may serve as a potential neuroimaging biomarker for tracking PD-FOG and distinguishing between PD subtypes.

The clinical value of combined detection of seven lung cancer-related autoantibodies in assisting the diagnosis of non-small-cell lung cancer.

Aim: Evaluate the clinical value of lung-cancer-related autoantibodies (CAGE, GAGE7, GBU4-5, MAGEA1, P53, PGP9.5, SOX2) in auxiliary diagnosis of non-small-cell lung cancer (NSCLC).Methods: We detected the concentrations of above 7 antibodies and lung cancer markers (CEA, NSE, CYFRE21-1) and drew area under the receiver characteristic curve of 316 patients.Results: The concentrations of CAGE, GBU4-5, MAGEA1, P53, PGP9.5 and SOX2 of significantly higher than other groups (p < 0.01). The sensitivity of different stages and pathological types of NSCLC consistent. Among them, the sensitivity of combined-detection in diagnosing adenocarcinoma and squamous cell carcinoma significantly better than CEA, NSE and CYFRA21-1.Conclusion: The combined detection has better efficacy in assisting the diagnosis of NSCLC and has certain clinical promotion and application value.

[Box: see text].

Photolithography-Free, Solution-Processable Perovskite Electrodes for High-Performance Organic Transistors.

Solution-processable electrodes are promising for next-generation electronics due to their simplicity, cost-effectiveness, and potential for large-area fabrication. However, current solution-processable electrodes based on conductive polymers, carbon-based compounds, and metal nanowires face challenges related to stability, patterning, and production scalability. Here we introduce a novel approach using 3D tin halide perovskites (THPs) combined with a photolithography-free solution patterning technique to fabricate solution-processed electrodes. We demonstrate the preparation of highly conductive CsSnI3 films (234.9 S cm-1) and the fabrication of patterned 35 × 35 perovskite electrode arrays on a 4-in. silicon wafer. These electrodes, used as source/drain electrodes in organic transistors, resulted in devices showing high uniformity and stability. This electrode fabrication strategy is also applicable to other 3D THPs like FASnI3 and MASnI3, showcasing versatility for diverse applications. The results highlight the feasibility and advantages of using 3D THPs as solution-processable electrodes, providing a new material system for the advancement of solution-processed electronics.

Generation Potential and Kinetics of Gaseous Hydrocarbons from Upper Paleozoic Carboniferous Benxi Formation Mudstone in Ordos Basin, China.

Industrial quantities of tight gas from the Carboniferous Benxi Formation have been found in the southern Ordos Basin. The source and contributions from mudstone and coal in the Benxi Formation to the tight gas are still unclear, and the hydrocarbon generation potential and kinetics of the Benxi Formation mudstone have rarely been reported, which has halted resource evaluation of tight gas. Confined pyrolysis experiments were performed to determine the yields and kinetic parameters for gaseous hydrocarbon formation for a representative sample of a Benxi Formation mudstone from the Ordos Basin, with a hydrogen index (HI) of 137 mg/g TOC and T max of 434 °C. The maximum yield of C1-C5 hydrocarbons is 143 mg/g TOC. For samples with similar HI, Upper Paleozoic mudstone samples might have a higher total gas generation potential than Upper Paleozoic coal samples because of the more reducing environment during mudstone deposition, which is beneficial for the preservation of sedimentary lipids. Even though the HI of Upper Paleozoic coals is apparently higher than that of Upper Paleozoic mudstones, they have a similar late gas generation potential. Basin modeling shows that the amount of natural gas generated from Benxi Formation mudstone increases southward. Coaly source rocks from the Ordos Basin with a lower oil generation potential have more negative δ13C1 values when the vitrinite reflectance is lower than 1.4-1.7%. This phenomenon might be related to the more negative δ13C of wet gas or the small hydrocarbon molecules incorporated into the kerogen compared with the components generating primary cracking gases. This study deepens the understanding of gaseous hydrocarbons generated from mudstone and coal in transitional depositional environments and provides the key parameters for tight gas resources in this area.

Insight into Oxygen Transport in Proton Exchange Membrane Water Electrolyzers by In Situ X-Ray Characterization.

The proton exchange membrane water electrolyzer (PEMWE) is one of the most promising electrochemical energy conversion devices for hydrogen production, while still limited by performance bottlenecks at high current densities, due to the lack of mass transfer insights. To investigate the mechanisms of oxygen transport inside the PEMWE at high current density and its relation to electrolytic performance. Operational in situ x-ray imaging is utilized to simultaneously characterize the bubble behavior and voltage response in a novel designed visual mini-cell, and it is identified that oxygen evolution and transport in the PEMWE follow the process of bubble nucleation, growth, and detachment. Based on the results of mini-cells with three porous transport layers (PTLs) up to 9 A cm-2 operation, it revealed that critical current densities exist for both carbon-based and titanium-based PTLs. Once exceeding the critical current density, the cell voltage can no longer be stabilized and the cell exhibits a significant oxygen overpotential. To illustrate this, the concept of interfacial separation zone (ISZ) is first proposed, which is an effective pathway for bubble growth and separation and the pattern of the ISZ exhibits specific regimes with the critical current density. Ultimately, a new approach for better understanding the mechanisms of oxygen transport is revealed.

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.

Tire Wear Chemicals in the Urban Atmosphere: Significant Contributions of Tire Wear Particles to PM2.5.

Tire wear particles (TWPs) containing tire wear chemicals (TWCs) are of global concern due to their large emissions and potential toxicity. However, TWP contributions to urban fine particles are poorly understood. Here, 72 paired gas-phase and PM2.5 samples were collected in the urban air of the Pearl River Delta, China. The concentrations of 54 compounds were determined, and 28 TWCs were detected with total concentrations of 3130-317,000 pg/m3. Most p-phenylenediamines (PPDs) were unstable in solvent, likely leading to their low detection rates. The TWCs were mainly (73 ± 26%) in the gas phase. 2-OH-benzothiazole contributed 82 ± 21% of the gas-phase TWCs and benzothiazole-2-sulfonic acid contributed 74 ± 18% of the TWCs in PM2.5. Guangzhou and Foshan were "hotspots" for atmospheric TWCs. Most TWC concentrations significantly correlated with the road length nearby. More particulate TWCs were observed than model predictions, probably due to the impacts of nonexchangeable portion and sampling artifacts. Source apportionment combined with characteristic molecular markers indicated that TWPs contributed 13 ± 7% of urban PM2.5. Our study demonstrates that TWPs are important contributors to urban air pollution that could pose risks to humans. There is an urgent need to develop strategies to decrease TWP emissions, along with broader urban air quality improvement strategies.

Network Pharmacology and Experimental Validation of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-155-5p.

BACKGROUND: Jinwei decoction can enhance the anti-inflammatory effect of glucocorticoid (GC) on chronic obstructive pulmonary disease (COPD) by restoring the activity of human histone deacetylase-2 (HDAC2). However the upstream mechanism of Jinwei decoction on HDAC2 expression is not clear. OBJECTIVE: To explore the target of Jinwei decoction to enhance the anti-inflammatory effect of GC on COPD through microRNA155-5p (miR-155-5p) by network pharmacology and experimental verification. METHODS: The TCMSP database was used to screen active ingredients and target genes of Jinwei decoction, and miRWalk2.0 was used to predict downstream target genes of miR-155-5p. COPD-related genes were identified by searching GeneCards, Grugbank and OMIM databases; Venny 2.1 was used to screen intersection genes; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of intersection genes were analyzed by R software. Protein-protein interactions (PPIs) were analyzed by Cytoscape 3.7.2 software to identify core genes. Finally, interactions between main compounds and potential targets were verified by molecular docking. A COPD cell model was established by 5% cigarette smoke extract (CSE)- induced bronchial epithelial cell (BEAS-2B), and the results of network pharmacology were verified by in vitro experiments. RESULTS: Two hundred thirty-one active ingredients, 352 Jinwei decoction drug targets, 5949 miR-155-5p target genes, 8286 COPD target genes, and 127 intersection genes were identified. Twelve core proteins of PPI networks may be involved. GO enrichment analysis showed that regulation of membrane potential， response to steroid hormone, and histone modification were involved; KEGG pathway enrichment analysis concentrated in the PI3K-Akt, mitogen-activated protein kinase (MAPK), HIF-1, and other signaling pathways. The molecular docking results showed that quercetin, luteolin and stigmasterol have higher affinity with PTGS2, HIF1A and AKT1. The results of cell experiments revealed that Jinwei decoction not only enhances the anti- inflammatory effect of GC in the COPD cell model but also reverses the high expression of miR-155-5p、PI3k、Akt, and low expression of HDAC2, thereby inhibiting the inflammatory response of COPD. CONCLUSION: Jinwei decoction can regulate HDAC2 activity and enhance the anti-inflammatory effect of GC on COPD by modulating miR-155-5p. Its mechanism of action may be related to its effect on the PI3K-Akt through miR-155-5p.

Management of post-radiation carotid blowout syndrome in patients with head and neck cancer: A systematic review.

BACKGROUND AND PURPOSE: Carotid blowout syndrome (CBS) is a rare but potentially life-threatening complication that can occur in patients with head and neck cancer (HNC), especially with a history of radiotherapy. This study aimed to review and initially compare managements for post-radiation CBS in patients with HNC. MATERIALS AND METHODS: A systematic review of published studies was performed. Information including management, survival, and complication were collected. RESULTS: A total of 39 articles and 917 cases were included in the systematic review. The interval between radiation therapy and CBS ranged from 1.2 years to 17.8 years. The managements of CBS included embolization, stent, bypass surgery, surgical ligation, electrocoagulation, flap coverage, arterial repair, and nasopharyngeal packing. The cumulative 30-day, 1-year, and 2-year overall survival rates were 85.2 %, 48.9 %, and 37.0 %, respectively, with a median survival time of 11.3 months. Disease progression and rebleeding were the most common death causes. The lowest rebleeding rate and neurologic complications rate were presented in cases receiving bypass surgery at 1.4 % and 10.8 %, respectively. The highest rebleeding rate of 35.6 % was showed in cases underwent stent, and the highest neurologic complications rate of 32.0 % was showed in cases underwent ligation. CONCLUSION: Post-radiation CBS in patients with HNC had a low survival rate and high complication rate. Rebleeding and neurologic complication were common complications. Endovascular embolization and stent were the mainstream management, and bypass surgery presented a promising outcome in survival and complication for selected patients.

Combined systemic inflammatory immune index and prognostic nutrition index as chemosensitivity and prognostic markers for locally advanced gastric cancer receiving neoadjuvant chemotherapy: a retrospective study.

BACKGROUND: The prognosis nutritional index (PNI) and the systemic inflammatory immunological index (SII) are characteristic indicators of the nutritional state and the systemic inflammatory response, respectively. However, there is an unknown combined effect of these indicators in the clinic. Therefore, the practicality of using the SII-PNI score to predict prognosis and tumor response of locally advanced gastric cancer (LAGC) following chemotherapy was the main focus of this investigation. METHODS: We retrospectively analyzed 181 patients with LAGC who underwent curative resection after neoadjuvant chemotherapy in a prospective study (NCT01516944). We divided these patients into tumour regression grade(TRG) 3 and non-TRG3 groups based on tumor response (AJCC/CAP guidelines). The SII and PNI were assessed and confirmed the cut-off values before treatment. The SII-PNI values varied from 0 to 2, with 2 being the high SII (≥ 471.5) as well as low PNI (≤ 48.6), a high SII or low PNI is represented by a 1 and neither is represented by a 0, respectively. RESULTS: 51 and 130 samples had TRG3 and non-TRG3 tumor responses respectively. Patients with TRG3 had substantially higher SII-PNI scores than those without TRG3 (p < 0.0001). Patients with greater SII-PNI scores had a poorer prognosis (p < 0.0001). The SII-PNI score was found to be an independent predictor of both overall survival (HR = 4.982, 95%CI: 1.890-10.234, p = 0.001) and disease-free survival (HR = 4.763, 95%CI: 1.994-13.903, p = 0.001) in a multivariate analysis. CONCLUSION: The clinical potential and accuracy of low-cost stratification based on SII-PNI score in forecasting tumor response and prognosis in LAGC is satisfactory.

Biodegradable Persistent Luminescence Nanoparticles as Pyroptosis Inducer for High-Efficiency Tumor Immunotherapy.

Pyroptosis possesses potent antitumor immune activity, making pyroptosis inducer development a promising direction for tumor immunotherapy. Persistent luminescence nanoparticles (PLNPs) are highly sensitive optical probes extensively employed in tumor diagnosis and therapy. However, a pyroptosis inducer based on PLNPs has not been reported yet. Herein, polyethylene glycol-poly lactic acid-co-glycolic acid (PEG-PLGA: PP) modified biodegradable CaS:Eu2+ (CSE@PP) PLNPs are synthesized as a pyroptosis inducer for tumor immunotherapy for the first time. The synthesized CSE@PP possesses biowindow persistent luminescence (PersL) and pH-responsive degradation properties, allowing it to remain stable under neutral pH but degrade when exposed to weak acid (pH < 6.5). During degradation within the tumor, CSE@PP constantly releases H2S and Ca2+ while its PersL gradually fades away. Thus, the PersL signal can self-monitor H2S and Ca2+ release. Furthermore, the released H2S and Ca2+ result in mitochondrial dysfunction and the inactivation of reactive oxygen species scavenging enzymes, synergistic facilitating intracellular oxidative stress, which induces caspase-1/GSDM-D dependent pyroptosis and subsequent antitumor immune responses. In a word, it is confirmed that CSE@PP can self-monitor H2S and Ca2+ release and pyroptosis-mediated tumor Immunotherapy. This work will facilitate biomedical applications of PLNPs and inspire pyroptosis-induced tumor immunotherapy.

Electron transport through two interacting channels in Azurin-based solid-state junctions.

The fundamental question of "what is the transport path of electrons through proteins?" initially introduced while studying long-range electron transfer between localized redox centers in proteins in vivo is also highly relevant to the transport properties of solid-state, dry metal-protein-metal junctions. Here, we report conductance measurements of such junctions, Au-(Azurin monolayer ensemble)-Bismuth (Bi) ones, with well-defined nanopore geometry and ~103 proteins/pore. Our results can be understood as follows. (1) Transport is via two interacting conducting channels, characterized by different spatial and time scales. The slow and spatially localized channel is associated with the Cu center of Azurin and the fast delocalized one with the protein's polypeptide matrix. Transport via the slow channel is by a sequential (noncoherent) process and in the second one by direct, off-resonant tunneling. (2) The two channels are capacitively coupled. Thus, with a change in charge occupation of the weakly coupled (metal center) channel, the broad energy level manifold, responsible for off-resonance tunneling, shifts, relative to the electrodes' Fermi levels. In this process, the off-resonance (fast) channel dominates transport, and the slow (redox) channel, while contributing only negligibly directly, significantly affects transport by intramolecular gating.

Tumor-associated macrophage-derived itaconic acid contributes to nasopharyngeal carcinoma progression by promoting immune escape via TET2.

Nasopharyngeal carcinoma (NPC) is a malignant tumor of epithelial origin in head and neck with high incidence rate in South China, Southeast Asia and North Africa. The intervention of tumor-associated macrophages (Mφs) (TAMs)-mediated immunosuppression is a potential therapeutic strategy against tumor metastasis, but the exact mechanisms of TAM-mediated immunosuppression in nasopharyngeal carcinoma are unclear. Furthermore, how TAM affects the occurrence and development of nasopharyngeal carcinoma through metabolism is rarely involved. In this work, we revealed that NPC cells promoted M2-type Mφ polarization and elevated itaconic acid (ITA) release. Also, TAMs facilitated NPC cell proliferation, migration, and invasion through immune response gene 1 (IRG1)-catalyzed ITA production. Then, IRG1-mediated ITA production in TAMs repressed the killing of CD8+ T cells, induced M2-type polarization of TAMs, and reduced the phagocytosis of TAMs. Moreover, we demonstrated ITA played a tumor immunosuppressive role by binding and dampening ten-eleven translocation-2 (TET2) expression. Finally, we proved that ITA promotes NPC growth by facilitating immune escape in CD34+ hematopoietic stem cell humanized mice. In Conclusion, TAM-derived ITA facilitated NPC progression by enhancing immune escape through targeting TET2, highlighting that interfering with the metabolic pathway of ITA may be a potential strategy for NPC treatment.

Surface Oxygen Vacancies and Corona Polarization of Bi4Ti3O12 Nanosheets for Synergistically Enhanced Sonopiezoelectric Therapy.

Sonopiezoelectric therapy, an ultrasound-activated piezoelectric nanomaterial for tumor treatment, has emerged as a novel alternative modality. However, the limited piezoelectric catalytic efficiency is a serious bottleneck for its practical application. Excellent piezoelectric catalysts with high piezoelectric coefficients, good deformability, large mechanical impact surface area, and abundant catalytically active sites still need to be developed urgently. In this study, the classical ferroelectric material, bismuth titanate (Bi4Ti3O12, BTO), is selected as a sonopiezoelectric sensitizer for tumor therapy. BTO generates electron-hole pairs under ultrasonic irradiation, which can react with the substrates in a sonocatalytic-driven redox reaction. Aiming to further improve the catalytic activity of BTO, modification of surface oxygen vacancies and treatment of corona polarization are envisioned in this study. Notably, modification of the surface oxygen vacancies reduces its bandgap and inhibits electron-hole recombination. Additionally, the corona polarization treatment immobilized the built-in electric field on BTO, further promoting the separation of electrons and holes. Consequently, these modifications greatly improve the sonocatalytic efficiency for in situ generation of cytotoxic ROS and CO, effectively eradicating the tumor.

Multi-Enzyme Mimetic MoCu Dual-Atom Nanozyme Triggering Oxidative Stress Cascade Amplification for High-Efficiency Synergistic Cancer Therapy.

Single-atom nanozymes (SAzymes) with ultrahigh atom utilization efficiency have been extensively applied in reactive oxygen species (ROS)-mediated cancer therapy. However, the high energy barriers of reaction intermediates on single-atom sites and the overexpressed antioxidants in the tumor microenvironment restrict the amplification of tumor oxidative stress, resulting in unsatisfactory therapeutic efficacy. Herein, we report a multi-enzyme mimetic MoCu dual-atom nanozyme (MoCu DAzyme) with various catalytic active sites, which exhibits peroxidase, oxidase, glutathione (GSH) oxidase, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mimicking activities. Compared with Mo SAzyme, the introduction of Cu atoms, formation of dual-atom sites, and synergetic catalytic effects among various active sites enhance substrate adsorption and reduce the energy barrier, thereby endowing MoCu DAzyme with stronger catalytic activities. Benefiting from the above enzyme-like activities, MoCu DAzyme can not only generate multiple ROS, but also deplete GSH and block its regeneration to trigger the cascade amplification of oxidative stress. Additionally, the strong optical absorption in the near-infrared II bio-window endows MoCu DAzyme with remarkable photothermal conversion performance. Consequently, MoCu DAzyme achieves high-efficiency synergistic cancer treatment incorporating collaborative catalytic therapy and photothermal therapy. This work will advance the therapeutic applications of DAzymes and provide valuable insights for nanocatalytic cancer therapy.

International Recommendations on Postoperative Management for Potentially Resectable Locally Recurrent Nasopharyngeal Carcinoma.

Locally recurrent nasopharyngeal carcinoma (NPC) presents substantial challenges in clinical management. Although postoperative re-irradiation (re-RT) has been acknowledged as a potential treatment option, standardized guidelines and consensus regarding the use of re-RT in this context are lacking. This article provides a comprehensive review and summary of international recommendations on postoperative management for potentially resectable locally recurrent NPC, with a special focus on postoperative re-RT. A thorough search was conducted to identify relevant studies on postoperative re-RT for locally recurrent NPC. Controversial issues, including resectability criteria, margin assessment, indications for postoperative re-RT, and the optimal dose and method of re-RT, were addressed through a Delphi consensus process. The consensus recommendations emphasize the need for a clearer and broader definition of resectability, highlighting the importance of achieving clear surgical margins, preferably through an en bloc approach with frozen section margin assessment. Furthermore, these guidelines suggest considering re-RT for patients with positive or close margins. Optimal postoperative re-RT doses typically range around 60 Gy, and hyperfractionation has shown promise in reducing toxicity. These guidelines aim to assist clinicians in making evidence-based decisions and improving patient outcomes in the management of potentially resectable locally recurrent NPC. By addressing key areas of controversy and providing recommendations on resectability, margin assessment, and re-RT parameters, these guidelines serve as a valuable resource for clinical experts involved in the treatment of locally recurrent NPC.

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.

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.

Optimal image quality and radiation doses with optimal tube voltages/currents for pediatric anthropomorphic phantom brains.

OBJECTIVE: Using pediatric anthropomorphic phantoms (APs), we aimed to determine the scanning tube voltage/current combinations that could achieve optimal image quality and avoid excessive radiation exposure in pediatric patients. MATERIALS AND METHODS: A 64-slice scanner was used to scan a standard test phantom to determine the volume CT dose indices (CTDIvol), and three pediatric anthropomorphic phantoms (APs) with highly accurate anatomy and tissue-equivalent materials were studied. These specialized APs represented the average 1-year-old, 5-year-old, and 10-year-old children, respectively. The physical phantoms were constructed with brain tissue-equivalent materials having a density of ρ = 1.07 g/cm3, comprising 22 numbered 2.54-cm-thick sections for the 1-year-old, 26 sections for the 5-year-old, and 32 sections for the 10-year-old. They were scanned to acquire brain CT images and determine the standard deviations (SDs), effective doses (EDs), and contrast-to noise ratios (CNRs). The APs were scanned by 21 combinations of tube voltages/currents (80, 100, or 120 kVp/10, 40, 80, 120, 150, 200, or 250 mA) and rotation time/pitch settings of 1 s/0.984:1. RESULTS: The optimal tube voltage/current combinations yielding optimal image quality were 80 kVp/80 mA for the 1-year-old AP; 80 kVp/120 mA for the 5-year-old AP; and 80 kVp/150 mA for the 10-year-old AP. Because these scanning tube voltages/currents yielded SDs, respectively, of 12.81, 13.09, and 12.26 HU, along with small EDs of 0.31, 0.34, and 0.31 mSv, these parameters and the induced values were expediently defined as optimal. CONCLUSIONS: The optimal tube voltages/currents that yielded optimal brain image quality, SDs, CNRs, and EDs herein are novel and essentially important. Clinical translation of these optimal values may allow CT diagnosis with low radiation doses to children's heads.

N6-methyladenosine modified circPAK2 promotes lymph node metastasis via targeting IGF2BPs/VEGFA signaling in gastric cancer.

Circular RNAs (circRNAs) have emerged as key regulators of cancer occurrence and progression, as well as promising biomarkers for cancer diagnosis and prognosis. However, the potential mechanisms of circRNAs implicated in lymph node (LN) metastasis of gastric cancer remain unclear. Herein, we identify a novel N6-methyladenosine (m6A) modified circRNA, circPAK2, which is significantly upregulated in gastric cancer tissues and metastatic LN tissues. Functionally, circPAK2 enhances the migration, invasion, lymphangiogenesis, angiogenesis, epithelial-mesenchymal transition (EMT), and metastasis of gastric cancer in vitro and in vivo. Mechanistically, circPAK2 is exported by YTH domain-containing protein 1 (YTHDC1) from the nucleus to the cytoplasm in an m6A methylation-dependent manner. Moreover, increased cytoplasmic circPAK2 interacts with Insulin-Like Growth Factor 2 mRNA-Binding Proteins (IGF2BPs) and forms a circPAK2/IGF2BPs/VEGFA complex to stabilize VEGFA mRNA, which contributes to gastric cancer vasculature formation and aggressiveness. Clinically, high circPAK2 expression is positively associated with LN metastasis and poor prognosis in gastric cancer. This study highlights m6A-modified circPAK2 as a key regulator of LN metastasis of gastric cancer, thus supporting circPAK2 as a promising therapeutic target and prognostic biomarker for gastric cancer.