Repairing Interfacial Defects in Self-Assembled Monolayers for High-Efficiency Perovskite Solar Cells and Organic Photovoltaics through the SAM@Pseudo-Planar Monolayer Strategy.

Lately, carbazole-based self-assembled monolayers (SAMs) are widely employed as effective hole-selective layers (HSLs) in inverted perovskite solar cells (PSCs). Nevertheless, these SAMs tend to aggregate in solvents due to their amphiphilic nature, hindering the formation of a monolayer on the ITO substrate and impeding effective passivation of deep defects in the perovskites. In this study, a series of new SAMs including DPA-B-PY, CBZ-B-PY, POZ-B-PY, POZ-PY, POZ-T-PY, and POZ-BT-PY are synthesized, which are employed as interfacial repairers and coated atop CNph SAM to form a robust CNph SAM@pseudo-planar monolayer as HSL in efficient inverted PSCs. The CNph SAM@pseudo-planar monolayer strategy enables a well-aligned interface with perovskites, synergistically promoting perovskite crystal growth, improving charge extraction/transport, and minimizing nonradiative interfacial recombination loss. As a result, the POZ-BT-PY-modified PSC realizes an impressively enhanced solar efficiency of up to 24.45% together with a fill factor of 82.63%. Furthermore, a wide bandgap PSC achieving over 19% efficiency. Upon treatment with the CNph SAM@pseudo-planar monolayer, also demonstrates a non-fullerene organic photovoltaics (OPVs) based on the PM6:BTP-eC9 blend, which achieves an efficiency of 17.07%. Importantly, these modified PSCs and OPVs all show remarkably improved stability under various testing conditions compared to their control counterparts.

Protein modification and degradation in ferroptosis.

Ferroptosis is a form of iron-related oxidative cell death governed by an integrated redox system, encompassing pro-oxidative proteins and antioxidative proteins. These proteins undergo precise control through diverse post-translational modifications, including ubiquitination, phosphorylation, acetylation, O-GlcNAcylation, SUMOylation, methylation, N-myristoylation, palmitoylation, and oxidative modification. These modifications play pivotal roles in regulating protein stability, activity, localization, and interactions, ultimately influencing both the buildup of iron and lipid peroxidation. In mammalian cells, regulators of ferroptosis typically undergo degradation via two principal pathways: the ubiquitin-proteasome system, which handles the majority of protein degradation, and autophagy, primarily targeting long-lived or aggregated proteins. This comprehensive review aims to summarize recent advances in the post-translational modification and degradation of proteins linked to ferroptosis. It also discusses strategies for modulating ferroptosis through protein modification and degradation systems, providing new insights into potential therapeutic applications for both cancer and non-neoplastic diseases.

Maternal linoleic acid-rich diet ameliorates bilirubin neurotoxicity in offspring mice.

Hyperbilirubinaemia is a prevalent condition during the neonatal period, and if not promptly and effectively managed, it can lead to severe bilirubin-induced neurotoxicity. Sunflower seeds are a nutrient-rich food source, particularly abundant in linoleic acid. Here, we provide compelling evidence that lactating maternal mice fed a sunflower seed diet experience enhanced neurological outcomes and increased survival rates in hyperbilirubinemic offspring. We assessed histomorphological indices, including cerebellar Nissl staining, and Calbindin staining, and hippocampal hematoxylin and eosin staining. Furthermore, we observed the transmission of linoleic acid, enriched in sunflower seeds, to offspring through lactation. The oral administration of linoleic acid-rich sunflower seed oil by lactating mothers significantly prolonged the survival time of hyperbilirubinemic offspring mice. Mechanistically, linoleic acid counteracts the bilirubin-induced accumulation of ubiquitinated proteins and neuronal cell death by activating autophagy. Collectively, these findings elucidate the novel role of a maternal linoleic acid-supplemented diet in promoting child health.

Overcrowded 14,14'-Bidibenzo[a,j]anthracenes: Challenges in Syntheses and Atypical Property of Lacking Symmetry-Breaking Charge Transfer (SBCT).

14,14'-Bidibenzo[a,j]anthracenes (BDBAs) were prepared by iridium-catalyzed annulation of 5,5'-biterphenylene with alkynes. The molecular geometries of overcrowded BDBAs were verified by X-ray crystallography. The two dibenzo[a,j]anthryl moieties are connected through the sterically hindered 14 positions, resulting in highly distorted molecular halves. The conformation with a small twist angle between two molecular halves can minimize steric conflicts between the substituents at 1 and 13 positions and the carbon atoms of the central axis, as well as steric clashes between those substituents. One such example is octafluoro-substituted BDBA, where the interplanar angle between two anthryl moieties is approximately 31° (currently the lowest reported value, cf. 81° in 9,9'-bianthracene). The intramolecular interactions and electronic couplings between two molecular halves resulted in upfield 1H NMR signals, redshifted absorption and emission bands, and a reduced HOMO-LUMO gap. Photodynamic investigations on BDBAs indicated that the formation of the conventional symmetry-breaking charge transfer (SBCT) state was suspended by restricted rocking around the central C-C bond. Such a mechanism associated with this highly constrained conformation was examined for the first time.

Cation Bimetallic MOF Anchored Carbon Fiber for Highly Efficient Microwave Absorption.

Carbon fiber (CF) is a potential microwave absorption (MA) material due to the strong dielectric loss. Nevertheless, owing to the high conductivity, poor impedance matching of carbon-based  materials results in limited MA performance. How to solve this problem and achieve excellent MA performance remains a principal challenge. Herein, taking full advantage of CF and excellent impedance matching of bimetallic metal-organic frameworks (MOF) derivatives layer, an excellent microwave absorber based on micron-scale 1D CF and NiCoMOF (CF@NiCoMOF-800) is developed. After adjusting the oxygen vacancies of the bimetallic MOF, the resultant microwave absorber presented excellent MA properties including the minimum reflection loss (RLmin) of -80.63 dB and wide effective absorption bandwidth (EAB) of 8.01 GHz when its mass percent is only 5 wt.% and the thickness is 2.59 mm. Simultaneously, the mechanical properties of the epoxy resin (EP)-based coating with this microwave absorber are effectively improved. The hardness (H), elastic modulus (E), bending strength, and compressive strength of CF@NiCoMOF-800/EP coating are 334 MPa, 5.56 GPa, 82.2 MPa, and 135.8 MPa, which is 38%, 15%, 106% and 53% higher than EP coating. This work provides a promising solution for carbon materials achieving excellent MA properties and mechanical properties.

Peelable Microwave Absorption Coating with Reusable and Anticorrosion Merits.

The peelable microwave absorption (MA) coating with reversible adhesion for stable presence on substrates and easy release without any residuals is highly desired in temporary electromagnetic protection, which can quickly enter and disengage the electromagnetic protection state according to the real-time changeable harsh surroundings. On the contrary, with the incorporation of abundant absorbent to achieve excellent MA ability, the tunable adhesion and sufficient cohesion are extremely challenging to fulfill the above requirement. The reported peelable coatings still have problems in controlling adhesion/cohesion strength and coating release, facing substantial residuals after peeling even using complex chemical modification or abundant additives. Herein, a peelable MA coating based on the block characteristics of polar and nonpolar segments of poly(styrene-(ethylene-co-butylene)-styrene) (SEBS) is successfully developed. The polyaniline-decorated carbon nanotube as a microwave absorber plays a positive influence on the adhesion/cohesion of the coating due to bonding interaction. The competitive effective absorption bandwidth (EAB) of 8.8 GHz and controllable yet reversible adhesion release on various substrates and complex surfaces have been achieved. The reusability endows peelable MA coating with 93% retention of EAB even after ten coating-peeling cycles. The coating with excellent chemical and adhesion stability can effectively protect substrates from salt/acid/alkali corrosion, showing over 98% retention of EAB even after 8 h of accelerated corrosion. Our peelable MA coating via a general yet reliable approach provides a prospect for temporary electromagnetic protection.

A New Series of Sandwich-Type 5,5'-Biterphenylenes: Synthetic Challenge, Structural Uniqueness and Photodynamics.

A new series of biaryls, bi-linear-terphenylenes (BLTPs), were prepared using the tert-butyllithium-mediated cyclization as the key synthetic step. The three-dimensional structures of the studied compounds were verified using X-ray crystallography and DFT calculations. Tetraaryl(ethynyl)-substituted BLTPs are highly crowded molecules, and the internal rotation around the central C-C bond is restricted due to a high barrier (>50 kcal/mol). These structures contain several aryl/terphenylenyl/aryl sandwiches, where the through-space π-π (TSPP) interactions are strongly reflected in the shielding of 1 H NMR chemical shifts, reduction of oxidation potentials, increasing aromaticity of the central six-membered ring and decreasing antiaromaticity of the four-membered rings in a terphenylenyl moiety based on NICS(0) and iso-chemical shielding surfaces. Despite the restricted C-C bond associated intramolecular TSPP interactions for BLTPs in the ground state, to our surprise, the electronic coupling between two linear terphenylenes (LTPs) in BLTPs in the excited state is weak, so that the excited-state behavior is dominated by the corresponding monomeric LTPs. In other words, all BLTPs undergo ultrafast relaxation dynamics via strong exciton-vibration coupling, acting as a blue-light absorber with essentially no emission.

Increased retinal venule diameter as a prognostic indicator for recurrent cerebrovascular events: a prospective observational study.

Microvasculature of the retina is considered an alternative marker of cerebral vascular risk in healthy populations. However, the ability of retinal vasculature changes, specifically focusing on retinal vessel diameter, to predict the recurrence of cerebrovascular events in patients with ischemic stroke has not been determined comprehensively. While previous studies have shown a link between retinal vessel diameter and recurrent cerebrovascular events, they have not incorporated this information into a predictive model. Therefore, this study aimed to investigate the relationship between retinal vessel diameter and subsequent cerebrovascular events in patients with acute ischemic stroke. Additionally, we sought to establish a predictive model by combining retinal veessel diameter with traditional risk factors. We performed a prospective observational study of 141 patients with acute ischemic stroke who were admitted to the First Affiliated Hospital of Jinan University. All of these patients underwent digital retinal imaging within 72 hours of admission and were followed up for 3 years. We found that, after adjusting for related risk factors, patients with acute ischemic stroke with mean arteriolar diameter within 0.5-1.0 disc diameters of the disc margin (MAD0.5-1.0DD) of ≥ 74.14 µm and mean venular diameter within 0.5-1.0 disc diameters of the disc margin (MVD0.5-1.0DD) of ≥ 83.91 µm tended to experience recurrent cerebrovascular events. We established three multivariate Cox proportional hazard regression models: model 1 included traditional risk factors, model 2 added MAD0.5-1.0DD to model 1, and model 3 added MVD0.5-1.0DD to model 1. Model 3 had the greatest potential to predict subsequent cerebrovascular events, followed by model 2, and finally model 1. These findings indicate that combining retinal venular or arteriolar diameter with traditional risk factors could improve the prediction of recurrent cerebrovascular events in patients with acute ischemic stroke, and that retinal imaging could be a useful and non-invasive method for identifying high-risk patients who require closer monitoring and more aggressive management.

The developments and future of drug detection technology for environmental samples / 中国法医学杂志

In recent years,the international drug control situation has become increasingly serious.According to the statistical data of the year 2021 from UNODC,in the past decade,the trafficking volume of traditional drug(such as methamphetamine,cannabis and cocaine)has continued to rise,new psychoactive substances(NPS)have emerged one after another,the drugs as well as their precursors and metabolites have become a new group of pollutants.They widely exist in environmental media such as water,air,sludge and soil,due to the manufacture and abuse of drugs,which endangers human and animal safety.Drug detection data from environmental samples can reflect the local drug use situation objectively,real-time,accurately and effectively,which is helpful to grasp the spatial distribution and time changes,monitor the development trends of drug abuse,assess the trend of drug abuse reasonably,and assist in combating related illegal and criminal activities through comprehensive data analysis.At present,sewage monitoring has become an important means of drug monitoring in countries around the world.Sewage testing can assess drug consumption in a place reasonably,and sewage network traceability technology can reduce the scope of regional investigation of drug manufacturing dens effectively,so as to combat accurately.Drug detection in the atmosphere,sludge and soil has been carried out in some foreign countries,but it has not been used as a long-term monitoring means.Long-term monitoring of drugs from the environment in a variety of ways not only helps to effectively update the drug situation in the region,but also to better understand local trends in drug use and identify new drugs of abuse.It will provide data support for more accurate monitoring and combating drug crimes in the future.This paper reviews the methods for detecting drugs and other related compounds in different environmental matrices including sewage,atmosphere and sludge in China and other countries,including the study on the sources and forms of related compounds in different environments,the preparation of different matrix samples and the quantitative analysis of drugs from environment,as well as the existing problems and shortcomings of various detection methods.Finally,the drug detection technology and comprehensive monitoring system in the environment are prospected.

Effect of hand hygiene intervention on healthcare-associated case infection incidence from 2014 to 2022 / 中国感染控制杂志

Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98％in 2014 to 85.01％in 2022(P＜0.001),and HA case infection incidence decreased from 1.21％to 0.83％(P＜0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P＜0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P＜0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.

Efficacy of two-staged laparoscopic Fowler-Stephens surgery through the Hay's triangle approach for the treat-ment of high cryptorchidism in children / 局解手术学杂志

Objective To analyze the efficacy of two-staged laparoscopic Fowler-Stephens surgery through the Hay's triangle approach for the treatment of high cryptorchidism in children.Methods The clinical data of 116 children with high cryptorchidism in our hospital were retrospectively analyzed,among which 43 children who underwent laparoscopic testicular extraction and fixation through the Hay's triangle approach were selected as the control group,and 73 children who underwent two-staged laparoscopic Fowler-Stephens surgery through the Hay's triangle approach were selected as the study group.The changes of sex hormone levels and testicular function before and after surgery were compared between the two groups.All patients were followed up for 6 months,and the testicular volume was reviewed and the occurrences of complications were recorded.Results There was no significant difference in the testicular volume before and after surgery between the two groups(P>0.05),and there was no significant difference in the total incidence of postoperative complications between the two groups(P>0.05).After surgery,the levels of serum follicle-stimulating hormone(FSH),estradiol(E2)and luteinizing hormone(LH)in the two groups were significantly lower than those before surgery(P<0.05),and the levels of serum testosterone(T),anti-Mullerian hormone(AMH),inhibin B(INHB)and INHB/FSH were significantly higher than those before surgery(P<0.05).However,there was no significant difference between the two groups(P>0.05).Conclusion The two-staged Fowler-Stephens surgery is effective in the treatment of high-risk cryptorchidism.It can establish a good collateral circulation by disconnection of spermatic cord vessels and gubernaculum testis,and the testis can be lowered to a satisfactory position in the scrotum.

Comparison of the effect of moxibustion at "Zusanli" (ST36) on the polarization of synovial macrophages of knee joints in rats with knee osteoarthritis and rheumatoid arthritis. / 艾灸"足三里"å¯¹è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žä¸Žç±»é£Žæ¹¿æ€§å ³èŠ‚ç‚Žå¤§é¼ è†å ³èŠ‚æ»‘è†œå·¨å™¬ç»†èƒžæžåŒ–çš„å½±å“çš„æ¯”è¾ƒç ”ç©¶.

OBJECTIVES: To observe the similarities and differences of effects of moxibustion at "Zusanli" (ST36) on target tissues and macrophages polarization in knee osteoarthritis (KOA) and rheumatoid arthritis (RA) rats, and to summarize its efficacy and characteristics. METHODS: Thirty rats were equally and randomly divided into control, KOA, RA, KOA+Moxi and RA+Moxi groups. The KOA model and RA model were induced by injection of sodium monoiodoacetate or Freund's complete adjuvant into the rats' knee joints, respectively. Rats of the KOA+Moxi and RA+Moxi groups received moxibustion stimulation at bilateral ST36 for 30 min, once a day for 21 days, beginning from the 7th day on after modeling. The contents of serum interleukin(IL)-1ß and IL-10 were detected by ELISA. Histopathological changes (Markin score of the knee cartilage and synovial pathology score) of the knee joints were observed after HE staining. The polarization state of M1 and M2 macrophages in the synovial tissue of the knee joints was assessed by detecting the expression of CD86 and CD206 after immunofluorescence staining. RESULTS: Compared with the control group, the content of serum IL-1ß, synovial pathology score, and synovial CD86 expression were significantly increased (P<0.01, P<0.05), while the content of serum IL-10 and synovial CD206 expression markedly decreased (P<0.01) in both KOA and RA groups；the Markin score was increased (P<0.01) in the KOA group. In comparison with the KOA group, the Markin score was obviously decreased (P<0.01), while the content of serum IL-10 and CD206 expression were apparently increased (P<0.01) in the KOA+Moxi group. No significant changes were found in the content of serum IL-1ß, synovial pathology score and CD86 expression in the KOA+Moxi group relevant to the KOA group. In comparison with the RA group, the content of serum IL-1ß, synovial pathology score, and CD86 expression were considerably decreased (P<0.01) in the RA+Moxi group. No marked differences were found in the serum IL-10 level, Markin score, and CD206 expression between RA+Moxi and RA model groups. The increased Markin score was significantly higher in the KOA group than in the RA group (P<0.01), but the increased synovial pathology score was significantly lower in the KOA group than in the RA group (P<0.01). Correspondingly, the effect of moxibustion at ST36 was significantly better in RA model than in KOA model in reducing serum IL-1ß (P<0.05). CONCLUSIONS: Moxibustion at ST36 can effectively reduce cartilage injury of knee joint in rats with KOA and reduce synovial injury in rats with RA, which may be related with its effects in lowering IL-1ß level in RA model by inhibiting the polarization of M1 macrophages, and up-regulating level of IL-10 in KOA model by promoting the polarization of M2 macrophages. However, the relevant mechanism needs to be further studied.

Permanent Shape Reconfiguration and Locally Reversible Actuation of a Carbon Nanotube/Ethylene Vinyl Acetate Copolymer Composite by Constructing a Dynamic Cross-Linked Network.

Given the rapid developments in modern devices, there is an urgent need for shape-memory polymer composites (SMPCs) in soft robots and other fields. However, it remains a challenge to endow SMPCs with both a reconfigurable permanent shape and a locally reversible shape transformation. Herein, a dynamic cross-linked network was facilely constructed in carbon nanotube/ethylene vinyl acetate copolymer (CNT/EVA) composites by designing the molecular structure of EVA. The CNT/EVA composite with 0.05 wt % CNT realized a steady-state temperature of ∼75 °C under 0.11 W/cm2 light intensity, which gave rise to remote actuation behavior. The dynamic cross-linked network along with a wide melting temperature offered opportunities for chemical and physical programming, thus realizing the achievement of the programmable three-dimensional (3D) structure and locally reversible actuation. Specifically, the CNT/EVA composite exhibited a superior permanent shape reconfiguration by activating the dynamic cross-linked network at 140 °C. The composite also showed a high reversible deformation rate of 11.1%. These features endowed the composites with the capability of transformation to 3D structure as well as locally reversible actuation performance. This work provides an attractive guideline for the future design of SMPCs with sophisticated structures and actuation capability.

Topological spatial differentiation via complex amplitude filtering in Fourier space.

Various approaches to implementing optical analog differentiation have been studied extensively and applied in edge-based image processing. Here, we report a topological optical differentiation scheme based on complex amplitude filtering, i.e., amplitude and spiral phase modulation in Fourier space. The isotropic and anisotropic multiple-order differentiation operations are demonstrated both theoretically and experimentally. Meanwhile, we also achieve multiline edge detection corresponding to the differential order for the amplitude and phase objects. This proof-of-principle work could open up new avenues for engineering a nanophotonic differentiator and realizing a more compact image-processing system.

Polyvinylpyrrolidone induced uniform coating of nickel nanoparticles on carbon nanotubes for efficient microwave absorption.

The impedance matching performance of carbon nanotubes (CNTs) can be effectively enhanced by developing a uniform magnetic impedance matching layer, which can take on critical significance in achieving the desirable microwave absorption (MA) performance. To obtain a uniform coating of Nickel (Ni) nanoparticles on CNTs, several methods have been developed (e.g., the γ-irradiation technique, electroless deposition, as well as microwave welding method). However, the intricate and complicated conditions of the above-mentioned methods limit their wide application. Therefore, controlling the distribution of Ni nanoparticles with the aid of a concise and effective method remains a great challenge. Herein, in view of the uniform dispersion effect of polyvinylpyrrolidone (PVP) on CNTs and its complexation with Ni ions, uniform coating of Ni nanoparticles on CNTs is well developed after it is introduced in the hydrothermal process. The prepared Ni/CNTs composites exhibited excellent MA performance in comparison with those of reported Ni/CNTs composites for the ideal impedance matching performance and microwave attenuation ability. When the filler content was only 15 wt%, the minimum reflection loss (RLmin) reached -39.5 dB, and the effective bandwidth (EB) with RL < -10 dB reached 5.2 GHz at the thickness of 1.15 mm. A scalable strategy of regulating the distribution of Ni nanoparticles and preparing a lightweight microwave absorber based on CNTs was developed in this study, which can serve as a vital guideline for preparing novel MA composite materials.

Mechanically Reinforced Rigid Polyimide Foam via Chemically Grafting Isocyanate Acid for Ultrabroad Band Microwave Absorption.

Polyimide (PI) foam with excellent microwave absorption (MA) performance and desirable compressive strength is highly critical and in demand in the structural MA components. Although the satisfactory MA performance of the present PI-based MA foams has been achieved by employing diverse methods, the relatively low compressive strength (∼KPa) restricted them from use as structural MA foams in practical application. Herein, isocyanate acid was introduced to the backbone of PI resin, which not only increased the PI backbone polarity and strength as rigid chain segment, but also served as a self-foaming component. The porous structure of PI foams was readily regulated by adjusting the water and carbon nanotube (CNT) filler contents of precursor dispersion. As a result of the improved polarity of the PI backbone resulted from the isocyanate group and high dielectric loss of CNT, the high compressive strength of 7.04 MPa and impressive MA property of the resultant PI foam with a low CNT loading ratio of 1.5 wt % were achieved, which were much higher than those reported previously. Especially, the effective absorption bandwidth (EAB) (RL < -10 dB) was up to 10.7 GHz (at the thickness of 3 mm), covering the C, X, and Ku bands simultaneously. Meanwhile, the EAB of the as-prepared PI foam retained 9.3 and 9.7 GHz even after being subjected to liquid nitrogen (-196 °C) and high temperature (300 °C) treatments due to the desirable stability of PI. In addition, the excellent thermal insulation resulted from the pores structure and low filler content was achieved, where the top surface only presented 60 °C after placing on 300 °C platform for 30 min. The high compressive strength, impressive MA property, and thermal insulation endowed the resultant CNT/PI foam with great potential application as structural MA foam in a harsh service environment.

Plumbagin is a novel GPX4 protein degrader that induces apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, remains a global health challenge requiring novel and effective therapeutic agents and approaches. Here, we found that a natural product plumbagin can inhibit the growth of HCC cells by inducing the downregulation of GPX4, but not other antioxidant enzymes such as CAT, SOD1, and TXN. Functionally, genetic silence of GPX4 enhances, whereas the overexpression of GPX4 inhibits plumbagin-induced apoptosis (rather than ferroptosis) in HCC cells. Furthermore, GPX4 protein specifically binds the deubiquitinase USP31, but not other deubiquitinases such as CYLD, USP1, USP14, USP20, USP30, USP38, UCHL1, UCHL3, and UCHL5. As an inhibitor of deubiquitinating enzymes, especially USP31, plumbagin induces ubiquitination of GPX4 and subsequent proteasomal degradation of GPX4 in HCC cells. Accordingly, plumbagin-mediated tumor suppression is also associated with the downregulation of GPX4 and the upregulation of apoptosis in a subcutaneous xenograft tumor model. Taken together, these findings demonstrate a novel anticancer mechanism of plumbagin by inducing GPX4 protein degradation.

Diagnosis of cervical lymph node metastasis with thyroid carcinoma by deep learning application to CT images.

Introduction: The incidence of thyroid diseases has increased in recent years, and cervical lymph node metastasis (LNM) is considered an important risk factor for locoregional recurrence. This study aims to develop a deep learning-based computer-aided diagnosis (CAD) method to diagnose cervical LNM with thyroid carcinoma on computed tomography (CT) images. Methods: A new deep learning framework guided by the analysis of CT data for automated detection and classification of LNs on CT images is proposed. The presented CAD system consists of two stages. First, an improved region-based detection network is designed to learn pyramidal features for detecting small nodes at different feature scales. The region proposals are constrained by the prior knowledge of the size and shape distributions of real nodes. Then, a residual network with an attention module is proposed to perform the classification of LNs. The attention module helps to classify LNs in the fine-grained domain, improving the whole classification network performance. Results: A total of 574 axial CT images (including 676 lymph nodes: 103 benign and 573 malignant lymph nodes) were retrieved from 196 patients who underwent CT for surgical planning. For detection, the data set was randomly subdivided into a training set (70%) and a testing set (30%), where each CT image was expanded to 20 images by rotation, mirror image, changing brightness, and Gaussian noise. The extended data set included 11,480 CT images. The proposed detection method outperformed three other detection architectures (average precision of 80.3%). For classification, ROI of lymph node metastasis labeled by radiologists were used to train the classification network. The 676 lymph nodes were randomly divided into 70% of the training set (73 benign and 401 malignant lymph nodes) and 30% of the test set (30 benign and 172 malignant lymph nodes). The classification method showed superior performance over other state-of-the-art methods with an accuracy of 96%, true positive and negative rates of 98.8 and 80%, respectively. It outperformed radiologists with an area under the curve of 0.894. Discussion: The extensive experiments verify the high efficiency of the proposed method. It is considered instrumental in a clinical setting to diagnose cervical LNM with thyroid carcinoma using preoperative CT images. The future research can consider adding radiologists' experience and domain knowledge into the deep-learning based CAD method to make it more clinically significant. Conclusion: The extensive experiments verify the high efficiency of the proposed method. It is considered instrumental in a clinical setting to diagnose cervical LNM with thyroid carcinoma using preoperative CT images.

Copper-dependent autophagic degradation of GPX4 drives ferroptosis.

Ferroptosis is a type of iron-dependent regulated cell death characterized by unrestricted lipid peroxidation and membrane damage. Although GPX4 (glutathione peroxidase 4) plays a master role in blocking ferroptosis by eliminating phospholipid hydroperoxides, the regulation of GPX4 remains poorly understood. Here, we report an unexpected role for copper in promoting ferroptotic cell death, but not cuproptosis, by inducing macroautophagic/autophagic degradation of GPX4. Copper chelators reduce ferroptosis sensitivity but do not inhibit other types of cell death, such as apoptosis, necroptosis, and alkaliptosis. Conversely, exogenous copper increases GPX4 ubiquitination and the formation of GPX4 aggregates by directly binding to GPX4 protein cysteines C107 and C148. TAX1BP1 (Tax1 binding protein 1) then acts as an autophagic receptor for GPX4 degradation and subsequent ferroptosis in response to copper stress. Consequently, copper enhances ferroptosis-mediated tumor suppression in a mouse model of pancreatic cancer tumor, whereas copper chelators attenuate experimental acute pancreatitis associated with ferroptosis. Taken together, these findings provide new insights into the link between metal stress and autophagy-dependent cell death.Abbreviations: CALCOCO2, calcium binding and coiled-coil domain 2; GPX4, glutathione peroxidase 4; MAP1LC3A/B, microtubule associated protein 1 light chain 3 alpha/beta; MPO, myeloperoxidase; NCOA4, nuclear receptor coactivator 4; OPTN, optineurin; PDAC, pancreatic ductal adenocarcinoma; RIPK1, receptor interacting serine/threonine kinase 1; ROS, reactive oxygen species; SLC40A1, solute carrier family 40 member 1; SQSTM1, sequestosome 1; TAX1BP1, Tax1 binding protein 1; TEPA, tetraethylenepentamine; TM, tetrathiomolybdate.