Devising Biocompatible, NIR-Activated Helical Pyroptosis Agents via 𝛑-Twisting Strategy for Promoting Antitumor Immunity.

Specifically controlling cell pyroptosis is advantageous for oncotherapy as it allows simultaneous ablation of primary tumors and activation of immunogenicity of tumor environment. Herein, a facile and robust strategy is presented to construct efficient NIR-activated helical pyroptosis agents (PyroAs) with negligible dark cytotoxicity. It is demonstrated that the construction of four intramolecular B-X bonds (X = O or N) within the BODIPY chromophore enforces a significant twisting of its π-conjugation, yielding a variety of helical HBD molecules with desired high photosensitivity and negligible dark toxicity. A robust approach is established to extend HBD into the near-infrared (NIR) region through site-selective incorporation of an electron-withdrawing ester moiety. It is also proved that targeted delivery of the NIR-activated HBD-ER to the endoplasmic reticulum (ER) specifically activates pyroptosis pathway by equipping it with an ER-targeting moiety. Finally, the favorable biocompatibility, excellent antitumor efficacy, and remarkable systematic immune response of this unique NIR-activated helical PyroAs are shown in vivo, demonstrating its potential application in solid tumor immunotherapy.

Enhancing corrosion resistance and self-healing of water-borne epoxy coatings using Ti3C2Tx-supported tannic acid on UIO-66-NH2.

In this study, we developed a composite material comprising UIO-66-NH2 encapsulated tannic acid (TA) loaded on Ti3C2Tx to improve the corrosion resistance of water borne epoxy (WEP) coatings. The successful synthesis of the material was determined by FT-IR, XRD, XPS, EDS, TGA, SEM and TEM characterization. Furthermore, ultraviolet (UV)tests were conducted to evaluate the release rate of TA at varying pH levels, revealing a release rate of approximately 95 % at pH 2. Electrochemical impedance spectroscopy (EIS) results over 60 d indicated that the Rc value of TU-T/WEP remained unchanged at 3.934 × 108, demonstrating a two-order magnitude increase compared to those of pure epoxy coatings, attributed to the synergistic active and passive protection of TU-T materials. The self-healing ability of the TU-T/WEP coating was validated through manual scratch experiments. Additionally, the EIS test showed that the Rc value of TU-T/WEP coating increased to 3.5 × 105 after 72 h, representing a two-order magnitude increase over that of the WEP coating alone. This study introduces a novel approach using green tannic acid as a corrosion inhibitor and amino-functionalized Ti3C2Tx with UIO-66-NH2 to enhance corrosion resistance and self-healing aproperties of coatings.

A nomogram for predicting nutritional risk before gastric cancer surgery.

BACKGROUND AND OBJECTIVES: Gastric cancer (GC) is the fourth leading cause of cancer death worldwide. Patients with GC have higher nutritional risk. This study aimed to construct a nomogram model for predicting preoperative nutritional risk in patients with GC in order to assess preoperative nutritional risk in patients more precisely. METHODS AND STUDY DESIGN: Patients diagnosed with GC and undergoing surgical treatment were included in this study. Data was collected through clinical information, laboratory testing, and radiomics-derived characteristics. Least absolute shrinkage selection operator (LASSO) regression analysis and multi-variable logistic regression were employed to construct a clinical prediction model, which takes the form of a logistic nomogram. The effectiveness of the nomogram model was evaluated using receiver operat-ing characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: A total of three predictors, namely body mass index (BMI), hemoglobin (Hb) and radiomics characteristic score (Radscore) were identified by LASSO regression analysis from a total of 21 variables studied. The model constructed using these three predictors displayed medium prediction ability. The area under the ROC curve was 0.895 (95% CI 0.844-0.945) in the training set, with a cutoff value of 0.651, precision of 0.957, and sensitivity of 0.718. In the validation set, it was 0.880 (95% CI 0.806-0.954), with a cutoff value of 0.655, precision of 0.930, and sensitivity of 0.698. DCA also confirmed the clinical benefit of the combined model. CONCLUSIONS: This simple and dependable nomogram model for clinical prediction can assist physicians in assessing preoperative nutritional risk in GC patients in a time-efficient and accurate manner to facilitate early identification and diagnosis.

Application and evaluation of minimally invasive surgical treatment options for early endometrial cancer.

BACKGROUND: Laparoscopic and robotic-assisted techniques have gained popularity, and endometrial cancer (EC) remains a significant health problem among women. OBJECTIVE: Minimally invasive surgical (MIS) therapy options for early endometrial cancer will be evaluated for their effectiveness and safety is the aim of this paper. We also investigate the differences in oncologic outcomes between MIS and open surgery (OS) for individuals with early-stage EC. The patient was diagnosed with early-stage EC and treated with laparoscopic surgery and was the focus of a retrospective analysis. 162 patients with early EC were analyzed, with diagnoses occurring between 2002 and 2022. METHODS: The patients were fragmented into two groups, one for OS and another for laparoscopic procedures. The total tumor excision and recurrence rates were identical across the two methods, indicating similar oncologic results. Rates of complications were likewise comparable across the two groups. RESULTS: The quality of life ratings of patients with robotic-assisted surgery was higher than those with laparoscopic surgery. Sixty-two (62.2%) of the 162 patients in this research had OS, whereas Fifty-six (57.8%) had MIS. The probability of recurrence of EC from stages III to IV was significanitly higher in women who had OS. CONCLUSION: Minimally invasive procedures were shown to be effective in treating early-stage EC, and while these findings provide support for their usage, larger multicenter randomized controlled studies are required to verify these results and further examine possible long-term advantages. Patients with early-stage EC, regardless of histologic type, had superior survival rates with MIS compared to OS.

Layer-Point Structure of Si3N4-NH2@GO for Improving Corrosion and Wear Resistance of Waterborne Epoxy Coating.

The use of graphene-based materials as anticorrosion coatings to protect metals is always a topic of discussion. In this work, silicon nitride (Si3N4) was aminated to improve its water dispersibility. Then it is attached to the graphene oxide (GO) surface to improve compatibility with epoxy (EP) resin as well as conductivity. The results of Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and zeta potentials test analyses indicated that Si3N4-NH2@GO with a layer-point structure has been successfully prepared. The corrosion resistance of the composite coatings was characterized by electrochemical impedance spectroscopy (EIS) and polarization curve analysis, and the wear resistance of the composite coatings was tested by friction and wear tests. The results showed that 1.0% Si3N4-NH2@GO has excellent corrosion and wear resistance. The use of Si3N4-NH2@GO layer point structures in this study broadens the way for GO applications.

Mining Technology Evaluation for Steep Coal Seams Based on a GA-BP Neural Network.

Many mines in Guizhou Province are in urgent need of renovation to ensure harmonious operation and prolong their lifespan. The key to successful renovation lies in the prudent selection of the appropriate mining technologies. Therefore, a comprehensive investigation was conducted on steep coal mines in Guizhou Province, and a comprehensive evaluation framework was established. Spearman correlation analysis was performed on various factors, selecting geological conditions and working face parameters with high correlation as the input variables and mining methods as the output variables. The optimal values of each hyperparameter were determined through orthogonal experiments, and the neural network structure was confirmed to be "17-9-3". Five variants of backpropagation (BP) algorithms were meticulously tested, and a genetic algorithm optimizing the BP neural network (GA-BP) was further assessed to improve the model's prediction accuracy. The accuracy of the model was evaluated via the coefficient of determination (R 2) and mean squared error (MSE). The research results indicated that the variable step-size algorithm with a momentum term (VSS + MT) was the optimal algorithm for the BP neural network. Additionally, the MSE values of the artificial neural network and GA-BP neural network in the testing phase were 0.06 and 0.04, with prediction success rates of 70 and 90%, respectively, and R 2 values of 0.79 and 0.85, respectively. Thus, the GA-BP neural network demonstrated superior performance. Finally, industrial application of the model was conducted on a working face in the Zhong-Yu coal mine. The evaluation index for the working face was "0.847, 0.09, 0.111", suggesting that fully mechanized mining should be adopted. The evaluation results were consistent with the current production status of the mine, verifying the reliability of the model in practical applications.

Glycine-Ti3C2Tx Hybrid Material Improves the Electrochemical Corrosion Resistance of a Water-Borne Epoxy Coating.

Improving the dispersibility and compatibility of nanomaterials in water-borne epoxy resins is an important means to improve the protection ability and corrosion resistance of coatings. In this study, glycine-functionalized Ti3C2Tx (GT) was used to prepare an epoxy composite coating. The results of Fourier transform infrared spectroscopy and X-ray diffraction showed that glycine was successfully modified. The scanning electron microscopy and transmission electron microscopy results showed that the aggregation of Ti3C2Tx was alleviated. Electrochemical impedance spectroscopy test results show that, after 60 days of immersion, GT coating still shows the best protection performance, and the composite coating |Z|f = 0.01 Hz is 3 orders of magnitude higher than that of the pure epoxy coating. This is mainly because, after adding glycine, the -COOH group on the surface of glycine binds to the -OH group on the surface of Ti3C2Tx, improving the aggregation of Ti3C2Tx itself. At the same time, the -NH group of glycine can also participate in the curing reaction of epoxy resin to strengthen the bonding strength between the coating and the metal. The good dispersion of GT in epoxy resin makes it fill the pores and holes left by epoxy resin curing and strengthen the corrosion resistance. The easy availability and green properties of glycine provide a simple and environmentally friendly method for the modification of Ti3C2Tx.

Disorder-Broadened Phase Boundary with Enhanced Amorphous Superconductivity in Pressurized In2Te5.

As an empirical tool in materials science and engineering, the iconic phase diagram owes its robustness and practicality to the topological characteristics rooted in the celebrated Gibbs phase law free variables (F) = components (C) - phases (P) + 2. When crossing the phase diagram boundary, the structure transition occurs abruptly, bringing about an instantaneous change in physical properties and limited controllability on the boundaries (F = 1). Here, the sharp phase boundary is expanded to an amorphous transition region (F = 2) by partially disrupting the long-range translational symmetry, leading to a sequential crystalline-amorphous-crystalline (CAC) transition in a pressurized In2Te5 single crystal. Through detailed in situ synchrotron diffraction, it is elucidated that the phase transition stems from the rotation of immobile blocks [In2Te2]2+, linked by hinge-like [Te3]2- trimers. Remarkably, within the amorphous region, the amorphous phase demonstrates a notable 25% increase of the superconducting transition temperature (Tc), while the carrier concentration remains relatively constant. Furthermore, a theoretical framework is proposed revealing that the unconventional boost in amorphous superconductivity might be attributed to an intensified electron correlation, triggered by a disorder-augmented multifractal behavior. These findings underscore the potential of disorder and prompt further exploration of unforeseen phenomena on the phase boundaries.

PAFAH2 suppresses synchronized ferroptosis to ameliorate acute kidney injury.

Synchronized ferroptosis contributes to nephron loss in acute kidney injury (AKI). However, the propagation signals and the underlying mechanisms of the synchronized ferroptosis for renal tubular injury remain unresolved. Here we report that platelet-activating factor (PAF) and PAF-like phospholipids (PAF-LPLs) mediated synchronized ferroptosis and contributed to AKI. The emergence of PAF and PAF-LPLs in ferroptosis caused the instability of biomembranes and signaled the cell death of neighboring cells. This cascade could be suppressed by PAF-acetylhydrolase (II) (PAFAH2) or by addition of antibodies against PAF. Genetic knockout or pharmacological inhibition of PAFAH2 increased PAF production, augmented synchronized ferroptosis and exacerbated ischemia/reperfusion (I/R)-induced AKI. Notably, intravenous administration of wild-type PAFAH2 protein, but not its enzymatically inactive mutants, prevented synchronized tubular cell death, nephron loss and AKI. Our findings offer an insight into the mechanisms of synchronized ferroptosis and suggest a possibility for the preventive intervention of AKI.

Exceptional Performance of Flame-Retardant Polyurethane Foam: The Suppression Effect on Explosion Pressure and Flame Propagation of Methane-Air Premixed Gas.

A self-built gas explosion testing platform was used to explore the quenching effect of flame-retardant polyurethane foam on a gas explosion. The effect of the foam's filling position and length on the explosion suppression performance was explored. The results demonstrate that polyurethane foam exhibits an excellent flame-quenching performance, with a minimum of a 5 cm length of porous material being sufficient to completely quench the flame during propagation. Furthermore, the attenuation function of this porous material on the pressure wave is insignificantly affected by the change in ignition energy. Compared with the explosive state of the empty pipeline, the best suppression effect is obtained when the polyurethane foam is 20 cm in length with a filling position at 1.8 m, and the maximum explosion pressure and maximum rise rate are attenuated by 86.2% and 84.7%, respectively. This work has practical significance for the application of porous materials in explosion suppression and explosion-proof technologies in the chemical industrial processing and oil (gas) storage fields.

Pressure-Induced Superconductivity and Topological Quantum Phase Transitions in the Topological Semimetal ZrTe2.

Topological transition metal dichalcogenides (TMDCs) have attracted much attention due to their potential applications in spintronics and quantum computations. In this work, the structural and electronic properties of topological TMDCs candidate ZrTe2 are systematically investigated under high pressure. A pressure-induced Lifshitz transition is evidenced by the change of charge carrier type as well as the Fermi surface. Superconductivity is observed at around 8.3 GPa without structural phase transition. A typical dome-shape phase diagram is obtained with the maximum Tc of 5.6 K for ZrTe2 . Furthermore, the theoretical calculations suggest the presence of multiple pressure-induced topological quantum phase transitions, which coexists with emergence of superconductivity. The results demonstrate that ZrTe2 with nontrivial topology of electronic states displays new ground states upon compression.

A hypoxia-activatable theranostic agent with intrinsic endoplasmic reticulum affinity and type-I photosensitivity.

A unique photosensitizer (PS), ERPS, with intrinsic endoplasmic reticulum (ER)-targeting ability and low oxygen-depletion type-I photosensitivity, is developed and used as a scaffold to construct an activatable theranostic agent for precise photodynamic therapy (PDT). The ER-targeted feature coupled with type-I photosensitivity endows ERPS with high phototoxicity toward tumor cells under both normoxic and hypoxic conditions. In addition, caging the phenol group of ERPS with a nitroreductase-sensitive triggering group provided a hypoxia-activatable PS (ERPSIm) that is encapsulated within a polymeric micelle to obtain a water-stable Im@NP nanoparticle for in vivo applications. After intravenous administration to 4T1 tumor-bearing BALB/c mice, Im@NP demonstrated highly efficient imaging-guided PDT ablation of implanted tumors. This is because the delivered ERPSIm cargos of Im@NP are specifically activated in the hypoxic microenvironment of solid tumor, and the activated ERPS molecules have efficient ER-targeted type-I photosensitivity.

Development and verification of a nomogram for predicting the prognosis of resectable gastric cancer with outlet obstruction.

BACKGROUND: The prognosis of patients with gastric cancer (GC) with gastric outlet obstruction (GOO) after gastrectomy is highly variable. In this study, we aimed to develop a nomogram to predict the prognosis of these patients. PATIENTS AND METHODS: Data from 218 GC patients with GOO who underwent gastrectomy at Sun Yat-sen University Cancer Center were retrospectively collected as a training cohort. The data of 59 patients with the same diagnosis who underwent gastrectomy at the First Affiliated Hospital of Guangxi Medical University were collected as an external verification cohort. A nomogram for the overall survival (OS) was developed using the Cox regression model in the training cohort, which was validated in a verification cohort. RESULTS: Multivariate analysis showed that the surgical procedure (P < 0.001), period of chemotherapy (P < 0.001), T stage (P = 0.006), N stage (P = 0.040), systemic immune-inflammatory index (SII) (P < 0.001), and fibrinogen level (P = 0.026) were independent factors affecting OS. The nomogram constructed on the aforementioned factors for predicting the 1- and 3-year OS achieved a Harrell's concordance index (C-index) of 0.756 and 0.763 for the training and verification cohorts, respectively. Compared with the 8th American Joint Committee on Cancer (AJCC) Tumour-Node-Metastasis (TNM) staging system, the nomogram had higher C-index values and areas under the curve (AUCs) and slightly higher net clinical benefit. CONCLUSION: Compared to the 8th AJCC staging system, the newly developed nomogram showed superior performance in predicting the survival of GC patients with GOO after gastrectomy.

Pressure-Tuning Superconductivity in Noncentrosymmetric Topological Materials ZrRuAs.

Recently, the hexagonal phase of ternary transition metal pnictides TT'X (T = Zr, Hf; T' = Ru; X = P, As), which are well-known noncentrosymmetric superconductors, were predicted to host nontrivial bulk topology. In this work, we systematically investigate the electronic responses of ZrRuAs to external pressure. At ambient pressure, ZrRuAs show superconductivity with Tc ~ 7.74 K, while a large upper critical field ~ 13.03 T is obtained for ZrRuAs, which is comparable to the weak-coupling Pauli limit. The resistivity of ZrRuAs exhibits a non-monotonic evolution with increasing pressure. The superconducting transition temperature Tc increases with applied pressure and reaches a maximum value of 7.93 K at 2.1 GPa, followed by a decrease. The nontrivial topology is robust and persists up to the high-pressure regime. Considering both robust superconductivity and intriguing topology in this material, our results could contribute to studies of the interplay between topological electronic states and superconductivity.

Critical role of guanylate binding protein 5 in tumor immune microenvironment and predictive value of immunotherapy response.

Background: The guanylate-binding proteins (GBPs) are the latest potential targets of immunotherapy. However, the role of GBP5 in pan-cancer, including colorectal cancer (CRC), remains unclear. This study aims to explore the effect of GBP5 on immunity in pan-cancer. Methods: Based on the RNA sequencing data of 33 cancers obtained from The Cancer Genome Atlas, we analyzed the clinical significance of GBPs and focused on the correlation between GBP5 and tumor microenvironment (TME). Immunotherapy cohort IMvigor210 was used to explore the relationship between treatment response and GBPs. Then, we further analyzed the expression of GBP5 in immune cells using single-cell transcriptome cohort GSE146771 and GSE132465 from the Gene Expression Omnibus database. Finally, a prognostic model based on GBP5 expression was established and validated. Results: We found that the expression of GBP3/4/5 is higher in colorectal cancer than in normal tissues, and GBP5 is a better predictor of good treatment response to immune checkpoint blockade than other GBPs. In most other cancers, GBP5 is also elevated in tumors compared with normal tissues and is associated with a better prognosis. As for TME, GBP5 is generally positively correlated with immune score, the level of tumor-infiltrating immune cells and immune-related genes. Single-cell analysis showed that GBP5 was mainly expressed in myeloid cells and T cells. The GBP5-related prognostic model we constructed in CRC can predict the survival of patients and propose some genes for subsequent research. Conclusion: This study revealed a strong correlation between GBP5 and immunity in generalized cancer and provided evidence that CRC may be a suitable cancer type for anti-GBP5 therapy.

Mitochondria-Driven Dye Rearrangement That Enables Spatiotemporally Controlled Photomedicine.

Reversibly controlling the dye arrangements in living systems has great potential to realize spatiotemporally controlled photomedicine. However, tuning or even maintaining a certain arrangement of dyes in a complex living environments is extremely challenging due to the interference of the various biological species. Herein, a conceptual supramolecular strategy to engineer a switchable photosensitizer (PS) via mitochondria-mediated dynamic interconversion between monomer and J-aggregation, enabling specific activation of the mitochondria-targeting photodynamic therapy (PDT) and hibernation after mitochondria damage is presented. The presented mitochondria-mediated "activate-then-hibernate" PS design enables a fascinating spatiotemporally controlled PDT in which spatially controlled mitochondrial-targeting enhances therapeutic efficacy and temporally controlled activation-then-hibernation averts off-target damage during PDT and tissue damage after clinical treatment, thus offering significant potential for biological research and clinical needs.

An oxygen-economical nano-photosensitizer with a high photodynamic therapeutic outcome via simultaneous reduction of the cellular respiration and oxygen depletion of PDT.

The development of photodynamic nanomedicines that can alleviate intratumoral oxygen deficiency during photodynamic therapy (PDT) is of great significance for improving the therapeutic outcome of solid tumors characterized by severe hypoxia. Massive oxygen consumption due to vigorous cellular respiration, i.e., mitochondrial-associated oxidative phosphorylation (OXPHOS), is another major cause of severe tumor hypoxia in addition to insufficient oxygen supply. Moreover, oxygen depletion during PDT further exacerbates the shortage of intratumoral oxygen. In this work, we engineered a novel oxygen-economical nano-photosensitizer via co-encapsulation of an OXPHOS inhibitor (ATO) and a newly developed type-I photosensitizer (IPS) into a polymeric micelle of PEG-b-PCL. By controlling the length of hydrophobic PCL segments, we successfully optimized the micelle size to around 30 nm for enhanced tumor penetration. The orchestration of the two functional components, ATO and IPS, can simultaneously hinder the two major tumor oxygen-consuming pathways, where ATO targets mitochondrial complex III to inhibit cellular respiration, while IPS generates ROS through a low oxygen-consuming type-I photochemical pathway, enabling remarkable PDT efficacies in both hypoxic cells and a 4T1 tumor-bearing BALB/c mouse model. This work sheds new light on the construction of nano-photosensitizers to rejuvenate PDT against hypoxic solid tumors.

Caging-Pnictogen-Induced Superconductivity in Skutterudites IrX3 (X = As, P).

Here, we report on a new kind of compound, XδIr4X12-δ (X = P, As), the first hole-doped skutterudites superconductor. We provide atomic-resolution images of the caging As atoms using scanning transmission electron microscopy (STEM). By inserting As atoms into the caged structure under a high pressure, superconductivity emerges with a maximum transition temperature (Tc) of 4.4 K (4.8 K) in IrAs3 (IrP3). In contrast to all of the electron-doped skutterudites, the electronic states around the Fermi level in XδIr4X12-δ are dominated by the caged X atom, which can be described by a simple body-centered tight-binding model, implying a distinct pairing mechanism. Our density functional theory (DFT) calculations reveal an intimate relationship between the pressure-dependent local-phonon mode and the enhancement of Tc. The discovery of XδIr4X12-δ provides an arena to investigate the uncharted territory of hole-doped skutterudites, and the method proposed here represents a new strategy of carrier doping in caged structures, without introducing extra elements.

Construction and Comprehensive Analysis of a circRNA-miRNA-mRNA Regulatory Network to Reveal the Pathogenesis of Hepatocellular Carcinoma.

Background: Circular RNAs (circRNAs) have been demonstrated to be closely related to the carcinogenesis of human cancer in recent years. However, the molecular mechanism of circRNAs in the pathogenesis of hepatocellular carcinoma (HCC) has not been fully elucidated. We aimed to identify critical circRNAs and explore their potential regulatory network in HCC. Methods: The robust rank aggregation (RRA) algorithm and weighted gene co-expression network analysis (WGCNA) were conducted to unearth the differentially expressed circRNAs (DEcircRNAs) in HCC. The expression levels of DEcircRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). A circRNA-miRNA-mRNA regulatory network was constructed by computational biology, and protein-protein interaction (PPI) network, functional enrichment analysis, survival analysis, and infiltrating immune cells analysis were performed to uncover the potential regulatory mechanisms of the network. Results: A total of 22 DEcircRNAs were screened out from four microarray datasets (GSE94508, GSE97332, GSE155949, and GSE164803) utilizing the RRA algorithm. Meanwhile, an HCC-related module containing 404 circRNAs was identified by WGCNA analysis. After intersection, only four circRNAs were recognized in both algorithms. Following qRT-PCR validation, three circRNAs (hsa_circRNA_091581, hsa_circRNA_066568, and hsa_circRNA_105031) were chosen for further analysis. As a result, a circRNA-miRNA-mRNA network containing three circRNAs, 17 miRNAs, and 222 mRNAs was established. Seven core genes (ESR1, BUB1, PRC1, LOX, CCT5, YWHAZ, and DDX39B) were determined from the PPI network of 222 mRNAs, and a circRNA-miRNA-hubgene network was also constructed. Functional enrichment analysis suggested that these seven hub genes were closely correlated with several cancer related pathways. Survival analysis revealed that the expression levels of the seven core genes were significantly associated with the prognosis of HCC patients. In addition, we also found that these seven hub genes were remarkably related to the infiltrating levels of immune cells. Conclusion: Our research identified three pivotal HCC-related circRNAs and provided novel insights into the underlying mechanisms of the circRNA-miRNA-mRNA regulatory network in HCC.