Reducing Emission Linewidth of Pure-Blue ZnSeTe Quantum Dots through Shell Engineering toward High Color Purity Light-Emitting Diodes.

High color purity blue quantum dot light-emitting diodes (QLEDs) have great potential applications in the field of ultra-high-definition display. However, the realization of eco-friendly pure-blue QLEDs with a narrow emission linewidth for high color purity remains a significant challenge. Herein, a strategy for fabricating high color purity and efficient pure-blue QLEDs based on ZnSeTe/ZnSe/ZnS quantum dots (QDs) is presented. It is found that by finely controlling the internal ZnSe shell thickness of the QDs, the emission linewidth can be narrowed by reducing the exciton-longitudinal optical phonon coupling and trap states in the QDs. Additionally, the regulation of the QD shell thickness can suppress the Förster energy transfer between QDs in the QLED emission layer, which will help to reduce the emission linewidth of the device. As a result, the fabricated pure-blue (452 nm) ZnSeTe QLED with ultra-narrow electroluminescence linewidth (22 nm) exhibit high color purity with the Commission Internationale de l'Eclairage chromatic coordinates of (0.148, 0.042) and considerable external quantum efficiency (18%). This work provides a demonstration of the preparation of pure-blue eco-friendly QLEDs with both high color purity and efficiency, and it is believed that it will accelerate the application process of eco-friendly QLEDs in ultra-high-definition displays.

Quaterization Derivatization with Bis(Pyridine) Iodine Tetrafluoroboride: High-Sensitivity Mass Spectrometric Analysis of Unsaturated Fatty Acids in Human Thyroid Tissues.

Accurate quantification of disease-related unsaturated fatty acids (UFAs) in biomedical samples plays an important role in clinical diagnosis. Here, we reported a quaterization derivatization-stable isotope labeling strategy for accurate quantitative analysis of UFAs by high-performance liquid chromatography-mass spectrometry. [d0]/[d10]-Bis(pyridine) iodine tetrafluoroboride ([d0]/[d10]-IPy2BF4) was employed as the carbon-carbon double bond derivatization reagent with high efficiency and high specificity, to introduce a charge tag on UFAs and avoid the interference of saturated fatty acids. After labeling, the detection sensitivity was significantly enhanced by up to three orders of magnitude compared to intact UFAs. The standard curves showed good linearity (R2 > 0.999) over a wide concentration range. This strategy was successfully applied to determine the content of 12 UFAs in human thyroid carcinoma and para-carcinoma tissues. A significant difference was found in the content of several UFAs between these two kinds of tissues (p < 0.05). These results indicated that the proposed strategy may be valuable for the discovery of abnormal UFA content in early clinical diagnosis.

Chloramine-T-Enabled Mass Spectrometric Analysis of C═C Isomers of Unsaturated Fatty Acids and Phosphatidylcholines in Human Thyroids.

Specific locations of carbon-carbon double bonds (C═C) in lipids often play an essential role in biological processes, and there has been a booming development in C═C composition analysis by mass spectrometry. However, a universal derivatization and fragmentation pattern for the annotation of C═C positions in lipids is still challenging and attractive. To expand this field in lipidomics, a flexible and convenient N-tosylaziridination method was developed, with high derivatization efficiency, sensitivity, and specificity. The derivatization was very fast (15 s), and C═C numbers as well as locations could be pinpointed specifically in tandem mass spectra. By qualitative and quantitative studies of paratumor and tumor thyroid tissues of human beings, the total content of unsaturated fatty acids was suggested to be increased in tumor tissues, and good correlations in and between lysophosphatidylcholines and phosphatidylcholines were revealed by Spearman analysis. Further studies of C═C isomers showed that n-6/n-3 ratios were closely associated with human thyroid tumorigenesis, and high ratios of n-6/n-3 isomers seemed to suffer a high risk of carcinogenesis. Other isomers were not very representative; however, C═C in n-9/n-7 could also be significant for oncology research. Generally, it is supposed that both total amounts and C═C isomer ratios were related to cancer, and N-tosylaziridine derivatization could provide an alternative strategy for the C═C isomer study of disease models.

Towards biomass production and wastewater treatment by enhancing the microalgae-based nutrients recovery from liquid digestate in an innovative photobioreactor integrated with dialysis bag.

Microalgae-based nutrients recovery from liquid anaerobic digestate of swine manure has been a hotspot in recent decades. Nevertheless, in consideration of the high NH4+-N content and poor light penetrability exhibited by the original liquid digestate, uneconomical pretreatment on liquid digestate including centrifugation and dilution are indispensable before microalgae cells inoculation. Herein, aiming at eliminating the energy-intensive and freshwater-consuming pretreatment on liquid digestate and enhancing microalgae growth, the dialysis bag which permits nutrients transferring across its wall surface whereas retains almost all matters characterized by impeding light transmission within the raw liquid digestate was integrated into a column photobioreactor (DB-PBR). Consequently, light availability of microalgae cells in DB-PBR was elevated remarkably and thus contributed to a 357.58% improvement on microalgae biomass concentration in DB-PBR than the conventional PBR under 80 µmol m-2 s-1. Likewise, superior nutrients removal efficiencies from liquid digestate were obtained in DB-PBR (NH4+-N: 74.84%, TP: 63.75%) over the conventional PBR (NH4+-N: 30.27%, TP: 16.86%). Furthermore, higher microalgae biomass concentration (1.87 g L-1) and nutrients removal efficiencies (NH4+-N: 95.12%, TP: 76.87%) were achieved in the DB-PBR by increasing the light intensity to 140 µmol m-2 s-1. More importantly, the DB-PBR may provide a simple and greener solution to purify other kinds of wastewater.

Direct Writing Large-Area Multi-Layer Ultrasmooth Films by an All-Solution Process: Toward High-Performance QLEDs.

With increasing the film area/layer, deteriorating in both smoothness and uniformity of thin-films frequently happen, which remains a barrier for making large-area quantum dot light-emitting diodes (QLEDs) by solution processes. Here, we demonstrated a facile all-solution process guided by the conical fiber array to write multi-layer ultrasmooth thin-films directly in centimeter scale. The side-by-side fibrous array helps to align surface tensions at the tri-phase contact line to facilitate large-area homogeneous deposition, which was verified by theoretical simulation. The Laplace pressure along individual conical fiber contributes to the steady liquid transfer. Thin-films with small roughness (<2.03 nm) and large-area (2×2 cm2 ) uniformity were prepared sequentially on the target substrate, leading to large-area high-performance QLEDs. The result offers new insights for fabricating large-area high-performance thin-film devices.

Simultaneous Analysis of Fatty Alcohols, Fatty Aldehydes, and Sterols in Thyroid Tissues by Electrospray Ionization-Ion Mobility-Mass Spectrometry Based on Charge Derivatization.

In this work, we developed a rapid and high-sensitivity method for simultaneous analyses of fatty alcohols, fatty aldehydes, and sterols by combining the optimized derivatization reaction with electrospray ionization-ion mobility-mass spectrometry (ESI-IM-MS). Pyridine and thionyl chloride were used as derivatization reagents as they were easily removed after the derivatization reaction and could generate permanently charged tags on different functional groups including hydroxyls and aldehydes. Through this one-step derivatization reaction, the sensitivity of detection for fatty alcohols, fatty aldehydes, and sterols was significantly increased. Moreover, the introduction of ion mobility spectrometry (IMS), offering an additional resolution power, ensured more sensitive and accurate detection of derivative products without increasing analytical time. Being connected with high-performance liquid chromatography, more than 15 kinds of compounds were analyzed within 4 min. Relative quantification using peak intensity ratios between d0-/d5-labeled ions were subsequently applied for analyzing these 15 kinds of compounds in human thyroid carcinoma and para-carcinoma tissues. The results showed significant differences in content of some analytes between these two kinds of tissues (p < 0.05). The correlations between most of the analytes in thyroid carcinoma tissues are better than the correlations in para-carcinoma tissues.

Tripartite motif containing 14: An oncogene in papillary thyroid carcinoma.

Tripartite motif (TRIM)-containing protein 14 (TRIM14) is implicated in many malignancies. Presently, we studied whether TRIM14 played a role in human papillary thyroid carcinoma (PTC). Herein, TRIM14 was up-regulated in tumor tissues when compared with normal thyroid samples. Among PTC patients, enhanced TRIM14 predicted short recurrence free survival (RFS) time. Then, we found that knockdown of TRIM14 in human PTC K1 cells inhibited cell proliferation, induced cell apoptosis and prevented the tumorigenicity in nude mice. On the contrary, TRIM14 overexpression in human PTC TPC1 cells promoted cell proliferation while inhibited cell apoptosis. TRIM14 exerted its oncogenic activities via promoting the activation of signal transducer and activator of transcription 3 (STAT3). Further, TRIM14 interacted with the suppressor of cytokine-signaling-1 (SOCS1), a negative regulator of STAT3 activation, and knockdown of TRIM14 inhibited SOCS1 ubiquitination. In conclusion, TRIM14 may be a prognostic factor and oncogene in PTC, and may be a potential target for PTC intervention.

Derivatization Strategy for Simultaneous Molecular Imaging of Phospholipids and Low-Abundance Free Fatty Acids in Thyroid Cancer Tissue Sections.

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has been applied in many fields for detecting and imaging a variety of metabolites. In cancer research, this fast-growing imaging method also helps to elucidate the connection between the changes of metabolites in the microenvironment and the proliferation and survival of cancer cells. Free fatty acids (FFAs) are a vital building block of phospholipids (PLs) that can serve as a second cellular messenger and provide nutrients in the cancer microenvironment. The metabolism process of FFAs and PLs is highly relevant to the initiation and progression of different cancers. To better understand the metabolism process in cancer tissues, simultaneously detecting and imaging FFAs and PLs is essential. Despite the crucial developments that have been performed in the field of lipids imaging, FFAs and PLs have rarely been detected and imaged simultaneously in positive ion mode with good detection sensitivity. In this work, an on-tissue derivatization method was used to add a permanently quaternary amine onto FFAs; then, the FFAs and PLs were simultaneously imaged in positive ion mode. The derivatized FFAs are suitable for detection in positive ion mode. In comparison with the traditional matrix and the previous derivatization method, our derivatization reagent has a higher sensitivity for imaging FFAs. In addition, for simultaneous imaging analysis of FFAs and PLs, the number of imaged FFAs and PLs is greater than that with the previous on-tissue derivatization method. This high-sensitivity on-tissue derivatization method was applied to detect and image PLs and fatty acids in thyroid cancer tissues. In the MSI experiment, FFA derivatives and PLs were imaged while molecular localization and tissue integrity were maintained. Meanwhile, the correlation between PLs and FFAs was also studied, and the results showed that the correlations between saturated FFAs of C16:0 and C18:0 and PLs are better than the correlations of unsaturated FFAs with PLs.

A Novel N Staging System for Predicting Survival in Patients with Medullary Thyroid Cancer.

INTRODUCTION: Despite the crucially prognostic value of lymph node metastasis (LNM) in patients with medullary thyroid cancer (MTC), only the LNM compartment alone was reflected in the 8th edition of the American Joint Committee on Cancer (AJCC) system. OBJECTIVE: This study aimed to incorporate the metastatic lymph node number and metastatic lymph node ratio to generate a more accurate and appropriate N staging system for patients with MTC based on recursive partitioning analysis. DESIGN, SETTING, AND PATIENTS: Two cohorts were included in the analysis, including 1374 MTC patients from the Surveillance, Epidemiology, and End Results database as the derivation cohort, and 164 patients from Fudan University Shanghai Cancer Center as the validation cohort. The predictive performance of the alternative proposed N staging system was compared with that of the 8th AJCC system by using the Harrell concordance index (C-index) and the area under the receiver operating characteristic curve (AUC). RESULTS: In the derivation cohort, the C-index and the AUC at 10 years were 0.778 and 0.789, respectively, for the novel N staging system, and 0.749 and 0.741, respectively, for the 8th AJCC N staging system. Similar trends were also observed in the validation cohort. The proposed N staging system had a better prognostic performance. CONCLUSION: With some improvements, the novel N staging system for MTC suggested from this research may be assessed for potential adoption in the next edition of the AJCC N staging system.

Ultrasmooth Quantum Dot Micropatterns by a Facile Controllable Liquid-Transfer Approach: Low-Cost Fabrication of High-Performance QLED.

Fabrication of a high quality quantum dot (QD) film is essentially important for a high-performance QD light emitting diode display (QLED) device. It is normally a high-cost and multiple-step solution-transfer process where large amounts of QDs were needed but with only limited usefulness. Thus, developing a simple, efficient, and low-cost approach to fabricate high-quality micropatterned QD film is urgently needed. Here, we proposed that the Chinese brush enables the controllable transfer of a QD solution directly onto a homogeneous and ultrasmooth micropatterned film in one step. It is proposed that the dynamic balance of QDs was enabled during the entire solution transfer process under the cooperative effect of Marangoni flow aroused by the asymmetric solvent evaporation and the Laplace pressure different by conical fibers. By this approach, QD nanoparticles were homogeneously transferred onto the desired area on the substrate. The as-prepared QLED devices show rather high performances with the current efficiencies of 72.38, 26.03, and 4.26 cd/A and external quantum efficiencies of 17.40, 18.96, and 6.20% for the green, red, and blue QLED devices, respectively. We envision that the result offers a low-cost, facile, and practically applicable solution-processing approach that works even in air for fabricating high-performance QLED devices.

Inverted structural quantum dot light-emitting diodes based on Al-doped ZnO electrode.

As an indium-free transparent conducting film, Al-doped zinc oxide (AZO) was prepared by magnetron sputtering technique, exhibiting good electrical, optical and surface characteristics. UPS/XPS measurements show that AZO and zinc oxide nanoparticles (ZnO NPs) have matched energy level that can facilitate the electron injection from AZO to ZnO NPs. Inverted structural green quantum dot light-emitting diodes based on AZO cathode were fabricated, which exhibits a maximum luminance up to 178 000 cd m-2, and a maximum current efficiency of 10.1 cd A-1. Therewith, combined with the simulated space-charge-limited current (SCLC) theory, the measured current density-voltage characteristics of charge-only devices were analyzed. It demonstrated that AZO and ZnO NPs had much better electron injection efficiency than ITO, showing a electron injection efficiency close to 100%. By studying the relationship between the electric field and the current density, the measured curve of AZO-based devices nearly fits the theoretical curve of SCLC and the AZO electrode has a better ohmic contact with ZnO NPs than ITO.

Repercussions of the Inner Shell Layer on the Performance of Cd-Free Quantum Dots and Their Light-Emitting Diodes.

Indium phosphide (InP) and zinc selenium tellurium (ZnSeTe) quantum dots (QDs) as less toxic alternatives have received substantial attention. The structure of QDs generally consists of a QD core, inner shell layer, and outer shell layer. We reckon that the inner shell layer, especially its components and thickness, have a significant influence on the optical and electronic performances of QDs. In this Perspective, we compare optical properties of these QDs with different inner shells and summarize how typical inner shell components and thickness influence their optical properties. The impact of the inner shell on the performance of QD light-emitting diodes (QLEDs) has also been discussed. The appropriate components and thickness of the inner shell both contribute to alleviate valence or lattice mismatch, thereby enhancing the performance of QDs. We expect that this Perspective could heighten awareness of the significance and impact of the inner shell layer in QDs and facilitate further development of QDs and QLEDs.

Ligand Engineering for Mitigating Exciton-Phonon Coupling in Mixed Halide Perovskite Nanocrystals.

The vulnerability of mixed halide perovskite nanocrystals (NCs) remains challenging because of the weak interaction between commonly employed ligands, oleic acid/oleylamine (OAm/OA) and halide anions, coupled with substantial surface phonon energy. Here, we introduce 3-aminopropyltriethoxysilane (APTES) as a capping ligand to modify CsPbBrI2 NCs to enhance the interactions between them. The optical properties have been significantly enhanced, and halide segregation has been suppressed, both of which can be attributed to the reduced phonon energy and exciton-phonon coupling strength. Moreover, these APTES-CsPbBrI2 NCs exhibit a broad color gamut and sustained color stability during long-term operation, indicating their promising potential in display technologies. This work may offer insights into surface engineering to enhance the properties and band stability of mixed halide perovskite NCs.

Deep convolutional neural network model ResNeSt for discrimination of papillary thyroid carcinomas and benign nodules in thyroid nodules diagnosed as atypia of undetermined significance.

Background: A deep convolutional neural network (DCNN) model was employed for the differentiation of thyroid nodules diagnosed as atypia of undetermined significance (AUS) according to the 2023 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The aim of this study was to investigate the efficiency of ResNeSt in improving the diagnostic accuracy of fine-needle aspiration (FNA) biopsy. Methods: Fragmented images were used to train and test DCNN models. A training dataset was built from 1,330 samples diagnosed as papillary thyroid carcinoma (PTC) or benign nodules, and a test dataset was built from 173 samples diagnosed as AUS. ResNeSt was trained and tested to provide a differentiation. With regard to AUS samples, the characteristics of the cell nuclei were compared using the Wilcoxon test. Results: The ResNeSt model achieved an accuracy of 92.49% (160/173) on fragmented images and 84.78% (39/46) from a patient wise viewpoint in discrimination of PTC and benign nodules in AUS nodules. The sensitivity and specificity of ResNeSt model were 95.79% and 88.46%. The κ value between ResNeSt and the pathological results was 0.847 (P<0.001). With regard to the cell nuclei of AUS nodules, both area and perimeter of malignant nodules were larger than those of benign ones, which were 2,340.00 (1,769.00, 2,807.00) vs. 1,941.00 (1,567.50, 2,455.75), P<0.001 and 190.46 (167.64, 208.46) vs. 171.71 (154.95, 193.65), P<0.001, respectively. The grayscale (0 for black, 255 for white) of malignant lesions was lower than that of benign ones, which was 37.52 (31.41, 46.67) vs. 45.84 (31.88, 57.36), P <0.001, indicating nuclear staining of malignant lesions were deeper than benign ones. Conclusions: In summary, the DCNN model ResNeSt showed great potential in discriminating thyroid nodules diagnosed as AUS. Among those nodules, malignant nodules showed larger and more deeply stained nuclei than benign nodules.

Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning.

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.

Cadmium-free quantum dot light emitting devices: energy-transfer realizing pure blue emission.

In this study, deep blue, pure electroluminescence (EL) at 441.5 nm from a ZnSe/ZnS quantum dot light-emitting device (QD-LED) is obtained by using poly (4-butylphenyl-diphenyl-amine) (poly-TPD) as the hole-transport layer (HTL) to open up the channel for energy transfer from poly-TPD to QDs. The emission originating from HTL is observed in the QD-LED with N,N'-bis (tolyl)-N,N'-diphenyl-1,1'-biphenyl-4,4'-diamine functionalized with two styryl groups (2-TPD) as the HTL due to inefficient energy-transfer from 2-TPD to QDs. The poly-TPD based device exhibits color-saturated blue emission with a narrow spectral bandwidth of full width at half maximum (~17.2 nm). These results explore the operating mechanism of the QD EL and signify a remarkable progress in deep blue QD-LEDs based on environmental-friendly QD materials.

Assessment of functional prognosis of anterior cruciate ligament reconstruction in athletes based on a body shape index.

BACKGROUND: A healthy body shape is essential to maintain athletes' sports level. At present, little is known about the effect of athletes' body shape on anterior cruciate ligament reconstruction (ACLR). Moreover, the relationship between body shape and variables such as knee joint function after operation and return to the field has not been well studied. AIM: To verify the relationship between a body shape index (ABSI) and the functional prognosis of the knee after ACLR in athletes with ACL injuries. METHODS: We reviewed 76 athletes with unilateral ACL ruptures who underwent ACLR surgery in the First Hospital of Shanxi Medical University between 2017 and 2020, with a follow-up period of more than 24 mo. First, all populations were divided into a High-ABSI group (ABSI > 0.835, n = 38) and a Low-ABSI group (ABSI < 0.835, n = 38) based on the arithmetic median (0.835) of ABSI values. The primary exposure factor was ABSI, and the outcome indicators were knee function scores as well as postoperative complications. The correlation between ABSI and postoperative knee function scores and postoperative complications after ACLR were analyzed using multifactorial logistic regression. RESULTS: The preoperative knee function scores of the two groups were similar. The surgery and postoperative rehabilitation exercises, range of motion (ROM) compliance rate, Lysholm score, and Knee Injury and Osteoarthritis Outcome Score of the two groups gradually increased, whereas the quadriceps atrophy index gradually decreased. The knee function scores were higher in the Low-ABSI group than in the High-ABSI group at the 24-mo postoperative follow-up (P < 0.05). In multifactorial logistic regression, ABSI was a risk factor of low knee joint function score after surgery, specifically low ROM scores (odds ratio [OR] = 1.31, 95% confidence interval [CI] [1.10-1.44]; P < 0.001), low quadriceps atrophy index (OR = 1.11, 95%CI [0.97-1.29]; P < 0.05), low Lysholm scores (OR = 2.34, 95%CI [1.78-2.94]; P < 0.001), low symptoms (OR = 1.14, 95%CI [1.02-1.34]; P < 0.05), low activity of daily living (OR = 1.34, 95%CI [1.18-1.65]; P < 0.05), low sports (OR = 2.47, 95%CI [1.78-2.84]; P < 0.001), and low quality of life (OR = 3.34, 95%CI [2.88-3.94]; P < 0.001). ABSI was also a risk factor for deep vein thrombosis of the lower limb (OR = 2.14, 95%CI [1.88-2.36], P < 0.05] and ACL recurrent rupture (OR = 1.24, 95%CI [0.98-1.44], P < 0.05) after ACLR. CONCLUSION: ABSI is a risk factor for the poor prognosis of knee function in ACL athletes after ACLR, and the risk of poor knee function after ACLR, deep vein thrombosis of lower limb, and ACL recurrent rupture gradually increases with the rise of ABSI.

ELISA-like QDB method to meet the emerging need of Her2 assessment for breast cancer patients.

Inherent issues of subjectivity and inconsistency have long plagued immunohistochemistry (IHC)-based Her2 assessment, leading to the repeated issuance of guidelines by the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) for its standardization for breast cancer patients. Yet, all these efforts may prove insufficient with the advent of Trastuzumab deruxtecan (T-Dxd), a drug with the promise to expand to tumors traditionally defined as Her2 negative (Her2-). In this study, we attempted to address these issues by exploring an ELISA-like quantitative dot blot (QDB) method as an alternative to IHC. The QDB method has been used to measure multiple protein biomarkers including ER, PR, Ki67, and cyclin D1 in breast cancer specimens. Using an independent cohort (cohort 2) of breast cancer formalin-fixed paraffin-embedded (FFPE) specimens, we validated cutoffs developed in cohort 1 (Yu et al., Scientific Reports 2020 10:10502) with overall 100% specificity (95% CI: 100-100) and 97.56% sensitivity (95% CI: 92.68-100) in cohort 2 against standard practice with the dichotomized absolutely quantitated values. Using the limit of detection (LOD) of the QDB method as the putative cutoff point, tumors with no Her2 expression were identified with the number comparable to those of IHC 0. Our results support further evaluation of the QDB method as an alternative to IHC to meet the emerging need of identifying tumors with low Her2 expression (Her2-low) in daily clinical practice.

HIF-1α drives resistance to ferroptosis in solid tumors by promoting lactate production and activating SLC1A1.

Solid tumors have developed robust ferroptosis resistance. The mechanism underlying ferroptosis resistance regulation in solid tumors, however, remains elusive. Here, we report that the hypoxic tumor microenvironment potently promotes ferroptosis resistance in solid tumors in a hypoxia-inducible factor 1α (HIF-1α)-dependent manner. In combination with HIF-2α, which promotes tumor ferroptosis under hypoxia, HIF-1α is the main driver of hypoxia-induced ferroptosis resistance. Mechanistically, HIF-1α-induced lactate contributes to ferroptosis resistance in a pH-dependent manner that is parallel to the classical SLC7A11 and FSP1 systems. In addition, HIF-1α also enhances transcription of SLC1A1, an important glutamate transporter, and promotes cystine uptake to promote ferroptosis resistance. In support of the role of hypoxia in ferroptosis resistance, silencing HIF-1α sensitizes mouse solid tumors to ferroptosis inducers. In conclusion, our results reveal a mechanism by which hypoxia drives ferroptosis resistance and identify the combination of hypoxia alleviation and ferroptosis induction as a promising therapeutic strategy for solid tumors.

SIRT6 drives sensitivity to ferroptosis in anaplastic thyroid cancer through NCOA4-dependent autophagy.

The sirtuin family has been reported to participate in the regulation of oxidative stress, cancer metabolism, aging, and so on. However, few studies have demonstrated its role in ferroptosis. Our previous studies confirmed that SIRT6 is upregulated in thyroid cancer and associated with cancer development by regulating glycolysis and autophagy. In this research, we aimed to elucidate the association between SIRT6 and ferroptosis. RSL3, erastin, ML210, and ML162 were applied to induce ferroptosis. Cell death and lipid peroxidation were measured by flow cytometry. We found that overexpression of SIRT6 significantly increased the sensitivity of cells to ferroptosis, whereas knockout of SIRT6 promoted resistance to ferroptosis. Furthermore, we demonstrated that SIRT6 induced NCOA4-dependent autophagic degradation of ferritin, thus driving sensitivity to ferroptosis. The clinically used ferroptosis inducer sulfasalazine showed promising therapeutic effects on SIRT6-upregulated thyroid cancer cells in vivo. In conclusion, our research demonstrated SIRT6-driven sensitivity to ferroptosis via NCOA4-dependent autophagy and proposed ferroptosis inducers as promising therapeutic agents for anaplastic thyroid cancer patients.