Ciprofloxacin is a novel anti-ferroptotic antibiotic.

Cancer patients undergoing chemotherapy are susceptible to various bacterial infections, necessitating prompt and precise antimicrobial treatment with antibiotics. Ciprofloxacin is a clinically utilized broad-spectrum antimicrobial agent known for its robust antiseptic activity. While ferroptosis, an oxidative form of cell death, has garnered attention as a promising avenue in cancer therapy, the potential impact of ciprofloxacin on the anticancer effects of ferroptosis remains unclear. This study seeks to investigate the potential influence of antibiotics on ferroptosis in human pancreatic ductal adenocarcinoma (PDAC) cells. Here, we report a previously unrecognized role of ciprofloxacin in inhibiting ferroptosis in human PDAC cells. Mechanistically, ciprofloxacin suppresses erastin-induced endoplasmic reticulum (ER) stress through the activating transcription factor 6 (ATF6) and ER to nucleus signaling 1 (ERN1) pathway. Excessive ER stress activation can trigger glutathione peroxidase 4 (GPX4) degradation through autophagic mechanisms. In contrast, ciprofloxacin enhances the protein stability of GPX4, a crucial regulator that suppresses ferroptosis by inhibiting lipid peroxidation. Thus, our study demonstrates the anti-ferroptotic role of ciprofloxacin, highlighting the importance of careful consideration when contemplating the combination of ciprofloxacin with specific ferroptosis inducers in PDAC patients.

Intrinsic Grain Boundary Structure and Enhanced Defect States in Air-Sensitive Polycrystalline 1T'-WTe2 Monolayer.

Monolayer WTe2 has attracted significant attention for its unconventional superconductivity and topological edge states. However, its air sensitivity poses challenges for studying intrinsic defect structures. This study addresses this issue using a custom-built inert gas interconnected system, and investigate the intrinsic grain boundary (GB) structures of monolayer polycrystalline 1T' WTe2 grown by nucleation-controlled chemical vapor deposition (CVD) method. These findings reveal that GBs in this system are predominantly governed by W-Te rhombi with saturated coordination, resulting in three specific GB prototypes without dislocation cores. The GBs exhibit anisotropic orientations influenced by kinks formed from these fundamental units, which in turn affect the distribution of grains in various shapes within polycrystalline flakes. Scanning tunneling microscopy/spectroscopy (STM/S) analysis further reveals metallic states along the intrinsic 120° twin grain boundary (TGB), consistent with computed band structures. This systematic exploration of GBs in air-sensitive 1T' WTe2 monolayers provides valuable insights into emerging GB-related phenomena.

Incidence and risk factors of postoperative pulmonary complications following total hip arthroplasty revision: a retrospective Nationwide Inpatient Sample database study.

BACKGROUND: Postoperative pulmonary complications (PPCs) are among the most severe complications following total hip arthroplasty revision (THAR), imposing significant burdens on individuals and society. This study examined the prevalence and risk factors of PPCs following THAR using the NIS database, identifying specific pulmonary complications (SPCs) and their associated risks, including pneumonia, acute respiratory failure (ARF), and pulmonary embolism (PE). METHODS: The National Inpatient Sample (NIS) database was used for this cross-sectional study. The analysis included patients undergoing THAR based on NIS from 2010 to 2019. Available data include demographic data, diagnostic and procedure codes, total charges, length of stay (LOS), hospital information, insurance information, and discharges. RESULTS: From the NIS database, a total of 112,735 THAR patients in total were extracted. After THAR surgery, there was a 2.62% overall incidence of PPCs. Patients with PPCs after THAR demonstrated increased LOS, total charges, usage of Medicare, and in-hospital mortality. The following variables have been determined as potential risk factors for PPCs: advanced age, pulmonary circulation disorders, fluid and electrolyte disorders, weight loss, congestive heart failure, metastatic cancer, other neurological disorders (encephalopathy, cerebral edema, multiple sclerosis etc.), coagulopathy, paralysis, chronic pulmonary disease, renal failure, acute heart failure, deep vein thrombosis, acute myocardial infarction, peripheral vascular disease, stroke, continuous trauma ventilation, cardiac arrest, blood transfusion, dislocation of joint, and hemorrhage. CONCLUSIONS: Our study revealed a 2.62% incidence of PPCs, with pneumonia, ARF, and PE accounting for 1.24%, 1.31%, and 0.41%, respectively. A multitude of risk factors for PPCs were identified, underscoring the importance of preoperative optimization to mitigate PPCs and enhance postoperative outcomes.

Alkaliptosis induction counteracts paclitaxel-resistant ovarian cancer cells via ATP6V0D1-mediated ABCB1 inhibition.

Paclitaxel serves as the cornerstone chemotherapy for ovarian cancer, yet its prolonged administration frequently culminates in drug resistance, presenting a substantial challenge. Here we reported that inducing alkaliptosis, rather than apoptosis or ferroptosis, effectively overcomes paclitaxel resistance. Mechanistically, ATPase H+ transporting V0 subunit D1 (ATP6V0D1), a key regulator of alkaliptosis, plays a pivotal role by mediating the downregulation of ATP-binding cassette subfamily B member 1 (ABCB1), a multidrug resistance protein. Both ATP6V0D1 overexpression through gene transfection and pharmacological enhancement of ATP6V0D1 protein stability using JTC801 effectively inhibit ABCB1 upregulation, resulting in growth inhibition in drug-resistant cells. Additionally, increasing intracellular pH to alkaline (pH 8.5) via sodium hydroxide application suppresses ABCB1 expression, whereas reducing the pH to acidic conditions (pH 6.5) with hydrochloric acid amplifies ABCB1 expression in drug-resistant cells. Collectively, these results indicate a potentially effective therapeutic strategy for targeting paclitaxel-resistant ovarian cancer by inducing ATP6V0D1-dependent alkaliptosis.

Landscape and prognostic values of lymphocytes in patients with hepatocellular carcinoma undergoing transarterial embolization.

Transarterial embolization, the first-line treatment for hepatocellular carcinoma, does not always lead to promising outcomes in all patients. A better understanding of how the immune lymphocyte changes after transarterial embolization might be the key to improve the efficacy of transarterial embolization. However, there are few studies evaluating immune lymphocytes in transarterial embolization patients. Therefore, we aimed to evaluate the short- and long-term effects of transarterial embolization on lymphocyte subsets in patients with hepatocellular carcinoma to identify those that predict transarterial embolization prognosis. Peripheral blood samples were collected from 44 patients with hepatocellular carcinoma at the following time points: 1 d before the initial transarterial embolization, 3 d after the initial transarterial embolization, and 1 mo after the initial transarterial embolization and subjected to peripheral blood mononuclear cell isolation and flow cytometry. Dynamic changes in 75 lymphocyte subsets were recorded, and their absolute counts were calculated. Tumor assessments were made every 4 to 6 wk via computed tomography or magnetic resonance imaging. Our results revealed that almost all lymphocyte subsets fluctuated 3 d after transarterial embolization, but only Tfh and B cells decreased 1 mo after transarterial embolization. Univariate and multivariate Cox regression showed that high levels of Th2 and conventional killer Vδ2 cells were associated with longer progressive-free survival after transarterial embolization. Longer overall survival after transarterial embolization was associated with high levels of Th17 and viral infection-specific Vδ1 cells and low levels of immature natural killer cells. In conclusion, transarterial embolization has a dynamic influence on the status of lymphocytes. Accordingly, several lymphocyte subsets can be used as prognostic markers for transarterial embolization.

On-device phase engineering.

In situ tailoring of two-dimensional materials' phases under external stimulus facilitates the manipulation of their properties for electronic, quantum and energy applications. However, current methods are mainly limited to the transitions among phases with unchanged chemical stoichiometry. Here we propose on-device phase engineering that allows us to realize various lattice phases with distinct chemical stoichiometries. Using palladium and selenide as a model system, we show that a PdSe2 channel with prepatterned Pd electrodes can be transformed into Pd17Se15 and Pd4Se by thermally tailoring the chemical composition ratio of the channel. Different phase configurations can be obtained by precisely controlling the thickness and spacing of the electrodes. The device can be thus engineered to implement versatile functions in situ, such as exhibiting superconducting behaviour and achieving ultralow-contact resistance, as well as customizing the synthesis of electrocatalysts. The proposed on-device phase engineering approach exhibits a universal mechanism and can be expanded to 29 element combinations between a metal and chalcogen. Our work highlights on-device phase engineering as a promising research approach through which to exploit fundamental properties as well as their applications.

Molecularly thin, two-dimensional all-organic perovskites.

Recently, the emergence of all-organic perovskites with three-dimensional (3D) structures has expanded the potential applications of perovskite materials. However, the synthesis and utilization of all-organic perovskites in 2D form remain largely unexplored because the design principle has not been developed. We present the successful synthesis of a metal-free 2D layered perovskite, denoted as the Choi-Loh van der Waals phase (CL-v phase), with the chemical formula A2B2X4, where A represents a larger-sized cation compared to B and X denotes an anion. The CL-v phase exhibits a van der Waals gap enabled by interlayer hydrogen bonding and can be exfoliated or grown as molecularly thin 2D organic crystals. The dielectric constants of the CL-v phase range from 4.8 to 5.5 and we demonstrate their potential as gate dielectrics for thin-film transistors.

Engineering a Hierarchy of Disorder: A New Route to Synthesize High-Performance 3D Nanoporous All-Carbon Materials*.

A new nanoporous amorphous carbon (NAC) structure that achieves both ultrahigh strength and high electrical conductivity, which are usually incompatible in porous materials is reported. By using modified spark plasma sintering, three amorphous carbon phases with different atomic bonding configurations are created. The composite consisted of an amorphous sp2-carbon matrix mixed with amorphous sp3-carbon and amorphous graphitic motif. NAC structure has an isotropic electrical conductivity of up to 12 000 S m-1, Young's modulus of up to ≈5 GPa, and Vickers hardness of over 900 MPa. These properties are superior to those of existing conductive nanoporous materials. Direct investigation of the multiscale structure of this material through transmission electron microscopy, electron energy loss spectroscopy, and machine learning-based electron tomography revealed that the origin of the remarkable material properties is the well-organized sp2/sp3 amorphous carbon phases with a core-shell-like architecture, where the sp3-rich carbon forms a resilient core surrounded by a conductive sp2-rich layer. This research not only introduces novel materials with exceptional properties but also opens new opportunities for exploring amorphous structures and designing high-performance materials.

Medical waste incineration fly ash-based magnesium potassium phosphate cement: Calcium-reinforced chlorine solidification/stabilization mechanism and optimized carbon reduction process strategy.

The traditional solidification/stabilization (S/S) technology, Ordinary Portland Cement (OPC), has been widely criticized due to its poor resistance to chloride and significant carbon emissions. Herein, a S/S strategy based on magnesium potassium phosphate cement (MKPC) was developed for the medical waste incineration fly ash (MFA) disposal, which harmonized the chlorine stabilization rate and potential carbon emissions. The in-situ XRD results indicated that the Cl- was efficiently immobilized in the MKPC system with coexisting Ca2+ by the formation of stable Ca5(PO4)3Cl through direct precipitation or intermediate transformation (the Cl- immobilization rate was up to 77.29%). Additionally, the MFA-based MKPC also demonstrated a compressive strength of up to 39.6 MPa, along with an immobilization rate exceeding 90% for heavy metals. Notably, despite the deterioration of the aforementioned S/S performances with increasing MFA incorporation, the potential carbon emissions associated with the entire S/S process were significantly reduced. According to the Life Cycle Assessment, the potential carbon emissions decreased to 8.35 × 102 kg CO2-eq when the MFA reached the blending equilibrium point (17.68 wt.%), while the Cl- immobilization rate still remained above 65%, achieving an acceptable equilibrium. This work proposes a low-carbon preparation strategy for MKPC that realizes chlorine stabilization, which is instructive for the design of S/S materials.

Rapid immobilization of arsenic in contaminated soils by microwave irradiation combined with magnetic biochar: Microwave-induced electron transfer for oxidation and immobilization of arsenic (III).

Biochar with adjustable redox activity is an effective strategy for immobilization of excess arsenic (As(III)) contaminated soil. However, biochar exhibits limitations in terms of electron transfer efficiency and immobilization efficiency due to insufficient activation energy. In this study, As(III) in the soil was rapidly immobilized by adding magnetic biochar (Fe-BC) and introducing microwave irradiation energy to enhance electron transport efficiency. The results showed that the pore structure and iron species (ZVI, Fe3O4) loaded onto the biochar could be modulated by controlling the temperature and time of microwave pyrolysis, which enhanced the microwave absorption capacity and the immobilization performance of As. After adding Fe-BC (10 wt%) and treating with microwave irradiation for 3 h, the content of As(III) in the soil was reduced to 54.56 %. Compared with the conventional heating treatment, the percentage of stabilized As (residual form) increased by 11.21 %. The localized hot spots formed through the absorption of microwave energy by biochar promote the formation of arsenic-containing mineral crystals (FeAsO4 and Fe3AsO7), thus enhancing the immobilization efficiency. In addition, microwave-induced electron transfer facilitated the oxidation of As(III) to As(V) by surface quinone and carbonyl groups on the Fe-BC. Density functional theory calculation further proved that the surface groups of the Fe-BC had a stronger electron-withdrawing ability under microwave irradiation, thereby promoting the adsorption and immobilization of As(III). This work provided a new perspective on the technology of rapid remediation of heavy metals contaminated soil using biochar.

On the topological surface states of the intrinsic magnetic topological insulator Mn-Bi-Te family.

We review recent progress in the electronic structure study of intrinsic magnetic topological insulators (MnBi2Te4) · (Bi2Te3)n ([Formula: see text]) family. Specifically, we focus on the ubiquitously (nearly) gapless behavior of the topological Dirac surface state observed by photoemission spectroscopy, even though a large Dirac gap is expected because of surface ferromagnetic order. The dichotomy between experiment and theory concerning this gap behavior is perhaps the most critical and puzzling question in this frontier. We discuss various proposals accounting for the lack of magnetic effect on the topological Dirac surface state, which are mainly categorized into two pictures, magnetic reconfiguration and topological surface state redistribution. Band engineering towards opening a magnetic gap of topological surface states provides great opportunities to realize quantized topological transport and axion electrodynamics at higher temperatures.

Targeting paraptosis in cancer: opportunities and challenges.

Cell death can be classified into two primary categories: accidental cell death and regulated cell death (RCD). Within RCD, there are distinct apoptotic and non-apoptotic cell death pathways. Among the various forms of non-apoptotic RCD, paraptosis stands out as a unique mechanism characterized by distinct morphological changes within cells. These alterations encompass cytoplasmic vacuolization, organelle swelling, notably in the endoplasmic reticulum and mitochondria, and the absence of typical apoptotic features, such as cell shrinkage and DNA fragmentation. Biochemically, paraptosis distinguishes itself by its independence from caspases, which are conventionally associated with apoptotic death. This intriguing cell death pathway can be initiated by various cellular stressors, including oxidative stress, protein misfolding, and specific chemical compounds. Dysregulated paraptosis plays a pivotal role in several critical cancer-related processes, such as autophagic degradation, drug resistance, and angiogenesis. This review provides a comprehensive overview of recent advancements in our understanding of the mechanisms and regulation of paraptosis. Additionally, it delves into the potential of paraptosis-related compounds for targeted cancer treatment, with the aim of enhancing treatment efficacy while minimizing harm to healthy cells.

Enhanced adsorption of aromatic VOCs on hydrophobic porous biochar produced via microwave rapid pyrolysis.

To customize biochar suitable for efficient adsorption of benzene derivatives, this study presents programmed microwave pyrolysis to produce hydrophobic porous biochar with low-dose ferric chloride. Designated control of the ramping rates in the carbonization stage and the temperatures in the activation stage were conducive to enlarging the specific surface area. Iron species, including amorphous iron minerals, could create small-scale hotspots during microwave pyrolysis to promote microporous structure development. Compared with conventional pyrolysis, programmed microwave pyrolysis could increase the specific surface area from 288.6 m2 g-1 to 455.9 m2 g-1 with a short heating time (15 min vs. 2 h) under 650 °C. Engineered biochar exhibited higher adsorption capacity for benzene and toluene (136.6 and 94.6 mg g-1), and lower adsorption capacity for water vapour (6.2 mg g-1). These findings provide an innovative design of engineered biochar for the adsorption of volatile organic compounds in the environment.

Ion-Conductive Metallo-Covalent Organic Frameworks Constructed with Tridentate Ligand and Zn Nodes.

Metallo-covalent organic frameworks (metallo-COFs) are organometallic scaffolds in which covalently bonded organic frameworks are interwoven with metal-coordinated pendant groups. Unlike the rigid ligands traditionally used for metal coordination, the utilization of "soft" ligands allows for configurable topology and pore structure in metallo-COFs, particularly when the ligands are generated in situ during dynamic synthesis. In this study, we present the rational synthesis of metallo-COFs based on pyridine-2,6-diimine (pdi), wherein the incorporation of Zn2+ ions and in situ-generated tridentate ligands (pdi) yields metallo-COFs with a square-like lattice. In the absence of Zn2+ ions, a topological isomer COF with a Kagome lattice is instead produced. Thus, the presence or absence of Zn2+ ions allows us to switch between two distinct morphologies corresponding to metallo-COF or COF. In comparison to Brønsted acid-catalyzed COF, which necessitates postmetallization for loading metal ions, the metal-templated COF synthesis method yields COFs with improved crystallinity and approximately 1:1 [Zn2+]/ligand composition. Building upon the metal-templated COF synthesis approach, we successfully synthesized pdiCOF-Zn-2 and pdiCOF-Zn-3, which possess square-like and honeycomb lattices, respectively. The enhanced crystallinity and near 1:1 [Zn2+]/ligand composition of pdiCOF-Zn-3 (honeycomb) facilitate its application as ion transport channels.

Identification of disease-related genes in Plasmodium berghei by network module analysis.

BACKGROUND: Plasmodium berghei has been used as a preferred model for studying human malaria, but only a limited number of disease-associated genes of P. berghei have been reported to date. Identification of new disease-related genes as many as possible will provide a landscape for better understanding the pathogenesis of P. berghei. METHODS: Network module analysis method was developed and applied to identify disease-related genes in P. berghei genome. Sequence feature identification, gene ontology annotation, and T-cell epitope analysis were performed on these genes to illustrate their functions in the pathogenesis of P. berghei. RESULTS: 33,314 genes were classified into 4,693 clusters. 4,127 genes shared by six malaria parasites were identified and are involved in many aspects of biological processes. Most of the known essential genes belong to shared genes. A total of 63 clusters consisting of 405 P. berghei genes were enriched in rodent malaria parasites. These genes participate in various stages of parasites such as liver stage development and immune evasion. Combination of these genes might be responsible for P. berghei infecting mice. Comparing with P. chabaudi, none of the clusters were specific to P. berghei. P. berghei lacks some proteins belonging to P. chabaudi and possesses some specific T-cell epitopes binding by class-I MHC, which might together contribute to the occurrence of experimental cerebral malaria (ECM). CONCLUSIONS: We successfully identified disease-associated P. berghei genes by network module analysis. These results will deepen understanding of the pathogenesis of P. berghei and provide candidate parasite genes for further ECM investigation.

Stack growth of wafer-scale van der Waals superconductor heterostructures.

Two-dimensional (2D) van der Waals (vdW) heterostructures have attracted considerable attention in recent years1-5. The most widely used method of fabrication is to stack mechanically exfoliated micrometre-sized flakes6-18, but this process is not scalable for practical applications. Despite thousands of 2D materials being created, using various stacking combinations1-3,19-21, hardly any large 2D superconductors can be stacked intact into vdW heterostructures, greatly restricting the applications for such devices. Here we report a high-to-low temperature strategy for controllably growing stacks of multiple-layered vdW superconductor heterostructure (vdWSH) films at a wafer scale. The number of layers of 2D superconductors in the vdWSHs can be precisely controlled, and we have successfully grown 27 double-block, 15 triple-block, 5 four-block and 3 five-block vdWSH films (where one block represents one 2D material). Morphological, spectroscopic and atomic-scale structural analyses reveal the presence of parallel, clean and atomically sharp vdW interfaces on a large scale, with very little contamination between neighbouring layers. The intact vdW interfaces allow us to achieve proximity-induced superconductivity and superconducting Josephson junctions on a centimetre scale. Our process for making multiple-layered vdWSHs can easily be generalized to other situations involving 2D materials, potentially accelerating the design of next-generation functional devices and applications22-24.

Electron Spin Decoherence Dynamics in Magnetic Manganese Hybrid Organic-Inorganic Crystals: The Effect of Lattice Dimensionality.

Organic-inorganic metal hybrids with their tailorable lattice dimensionality and intrinsic spin-splitting properties are interesting material platforms for spintronic applications. While the spin decoherence process is extensively studied in lead- and tin-based hybrids, these systems generally show short spin decoherence lifetimes, and their correlation with the lattice framework is still not well-understood. Herein, we synthesized magnetic manganese hybrid single crystals of (4-fluorobenzylamine)2MnCl4, ((R)-3-fluoropyrrolidinium)MnCl3, and (pyrrolidinium)2MnCl4, which represent a change in lattice dimensionality from 2D and 1D to 0D, and studied their spin decoherence processes using continuous-wave electron spin resonance spectroscopy. All manganese hybrids exhibit nanosecond-scale spin decoherence time τ2 dominated by the symmetry-directed spin exchange interaction strengths of Mn2+-Mn2+ pairs, which is much longer than lead- and tin-based metal hybrids. In contrast to the similar temperature variation laws of τ2 in 2D and 0D structures, which first increase and gradually drop afterward, the 1D structure presents a monotonous rise of τ2 with the temperatures, indicating the strong correlation of spin decoherence with the lattice rigidity of the inorganic framework. This is also rationalized on the basis that the spin decoherence is governed by the competitive contributions from motional narrowing (prolonging the τ2) and electron-phonon coupling interaction (shortening the τ2), both of which are thermally activated, with the difference that the former is more pronounced in rigid crystalline lattices.