Correlation among post-surgery recurrence of CRSwNP and TCM syndromes and tissue inflammatory cell infiltration type: a study protocol.

BACKGROUND: Functional endoscopic sinus surgery is a principal option for treating chronic rhinosinusitis with nasal polyps (CRSwNP) after medication failures. Unfortunately, some patients still have unsatisfactory postoperative recovery. The type of inflammatory cell infiltration in nasal polyp tissue has been reported available for recurrence prediction. As it is invasive and time-consuming, this technique is hard to promote clinically under the existing technical conditions. And during the course of clinical treatment, we have noted that differences in the postoperative recurrence rate of patients present among different traditional Chinese medicine syndrome types. METHODS AND ANALYSIS: This is a non-randomized, single-center, and prospective cohort study started in Chengdu Sichuan Province, People's Republic of China, in January 2021. A total of 200 participants will be recruited from patients who are diagnosed with CRSwNP and prepared for functional endoscopic sinus surgery. We collect preoperative data which includes general information, medical history, TCM syndromes, visual analogue scale (VAS) of subjective symptoms, Lund-Kennedy endoscopic score, and Lund-Mackay score of computed tomography (CT) scanning of sinuses. We acquire the VAS score and Lund-Kennedy score of subjective symptoms through multiple planned follow-up after surgery. After 1 year of follow-up, the recurrence rate will be calculated, and the curative effect will be assessed. Meanwhile, the patients' pathological sections will be sorted out, and inflammatory cell infiltration will be analyzed. Statistical analysis will be carried out to evaluate the correlation among CRSwNP recurrence and TCM syndrome types and tissue inflammatory cell infiltration types. Then we will establish a predictive model for CRSwNP recurrence. Analyses of survey data include descriptive and inferential statistical approaches. DISCUSSION: This is the first prospective cohort study on investigating the correlation of CRSwNP recurrence with TCM syndrome types and tissue inflammatory cell infiltration types. Through this study, we hope to discover a new and simple, effective, and noninvasive way to predict the recurrence rate rapidly after CRSwNP and provide reference for the intervention timing of traditional Chinese medicine application, thereby achieving customized diagnosis and treatment, minimizing risks of surgical events, and delaying postoperative recurrence of CRSwNP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ChiCTR2100041646.

ABCB1-mediated docetaxel resistance reversed by erastin in prostate cancer.

Docetaxel (Doc) currently serves as the primary first-line treatment for patients with castrate-resistant prostate cancer (CRPC). Erastin, a small molecule compound, can trigger inhibition of the cystine-glutamate reverse transport system and other pathways, leading to iron-dependent cell death (ferroptosis). Beyond its role in inducing cancer cell death, erastin demonstrates potential when combined with chemotherapy drugs to heighten cancer cell drug susceptibility. However, the augmentation by erastin of the effects of Doc treatment on prostate cancer, and the underlying mechanisms involved, remain unclear. In the present study, we determined the role and the underlying molecular mechanism of erastin against CRPC. The results showed that CRPC cell lines were resistant to Doc, and the expression of ferroptosis-related factors in drug-resistant cell lines was downregulated. Erastin, in synergy with Doc, exerts a pro-apoptotic effect. Erastin significantly inhibited the activity of ATP-binding cassette subfamily B member 1 (ABCB1) but did not change its protein expression and localization. Finally, in mice, erastin treatment dramatically reduced tumor growth in vivo. Taken together, our findings demonstrate that erastin enhances Doc-induced apoptosis to a certain extent and reverses Doc resistance in prostate cancer by inhibiting the activity of multidrug-resistant protein ABCB1.

One-Component Cationic Lipids for Systemic mRNA Delivery to Splenic T Cells.

Unlocking the full potential of mRNA immunotherapy necessitates targeted delivery to specific cell subsets in the spleen. Four-component lipid nanoparticles (LNPs) utilized in numerous clinical trials are primarily limited in hepatocyte and muscular targeting, highlighting the imperative demand for targeted and simplified non-liver mRNA delivery systems. Herein, we report the rational design of one-component ionizable cationic lipids to selectively deliver mRNA to the spleen and T cells with high efficacy. Unlike the tertiary amine-based ionizable lipids involved in LNPs, the proposed cationic lipids rich in secondary amines can efficiently deliver mRNA both in vitro and in vivo as the standalone carriers. Furthermore, these vectors facilitate efficacious mRNA delivery to the T cell subsets following intravenous administration, demonstrating substantial potential for advancing immunotherapy applications. This straightforward strategy extends the utility of lipid family for extrahepatic mRNA delivery, offering new insights into vector development beyond LNPs to further the field of precise mRNA therapy.

Lithium Superionic Conductive Nanofiber-Reinforcing High-Performance Polymer Electrolytes for Solid-State Batteries.

Although composite solid-state electrolytes (CSEs) are considered promising ionic conductors for high-energy lithium metal batteries, their unsatisfactory ionic conductivity, low mechanical strength, poor thermal stability, and narrow voltage window limit their practical applications. We have prepared a new lithium superionic conductor (Li-HA-F) with an ultralong nanofiber structure and ultrahigh room-temperature ionic conductivity (12.6 mS cm-1). When it is directly coupled with a typical poly(ethylene oxide)-based solid electrolyte, the Li-HA-F nanofibers endow the resulting CSE with high ionic conductivity (4.0 × 10-4 S cm-1 at 30 °C), large Li+ transference number (0.66), and wide voltage window (5.2 V). Detailed experiments and theoretical calculations reveal that Li-HA-F supplies continuous dual-conductive pathways and results in stable LiF-rich interfaces, leading to its excellent performance. Moreover, the Li-HA-F nanofiber-reinforced CSE exhibits good heat/flame resistance and flexibility, with a high breaking strength (9.66 MPa). As a result, the Li/Li half cells fabricated with the Li-HA-F CSE exhibit good stability over 2000 h with a high critical current density of 1.4 mA cm-2. Furthermore, the LiFePO4/Li-HA-F CSE/Li and LiNi0.8Co0.1Mn0.1O2/Li-HA-F CSE/Li solid-state batteries deliver high reversible capacities over a wide temperature range with a good cycling performance.

Discovery of Highly Potent Small-Molecule PD-1/PD-L1 Inhibitors with a Novel Scaffold for Cancer Immunotherapy.

Inhibition of the PD-1/PD-L1 interaction through small-molecule inhibitors is a promising therapeutic approach in cancer immunotherapy. Herein, we utilized BMS-202 as the lead compound to develop a series of novel PD-1/PD-L1 small-molecule inhibitors with a naphthyridin scaffold. Among these compounds, X14 displayed the most potent inhibitory activity for the PD-1/PD-L1 interaction (IC50 = 15.73 nM). Furthermore, X14 exhibited good binding affinity to both human PD-L1 (KD = 14.62 nM) and mouse PD-L1 (KD = 392 nM). In particular, X14 showed favorable pharmacokinetic properties (oral bioavailability, F = 58.0%). In the 4T1 (mouse breast cancer cells) syngeneic mouse model, intragastric administration of X14 at 10 mg/kg displayed significant antitumor efficacy (TGI = 66%). Mechanistic investigations revealed that X14 effectively enhanced T-cell infiltration within the tumor microenvironment. Our study demonstrates that compound X14 exhibits potential as a candidate compound for the development of orally effective small-molecule inhibitors targeting PD-1/PD-L1.

Carvedilol induces pyroptosis through NLRP3-caspase1-ASC inflammasome by nuclear migration of NF-κB in prostate cancer models.

BACKGROUND: Pyroptosis is an inflammatory type of programmed cell death, and could overcome the drug-resistance induced by anti-apoptotic effect of cancers. Carvedilol (CVL), a ß-adrenergic receptors antagonist, has shown anti-inflammatory response and anti-cancer effect. The aim of this study is to investigate whether pyroptosis can be activated by CVL in prostate cancer (PCa). METHODS AND RESULTS: Datasets were used to analyze the expressions of pyroptosis-related proteins. Intracellular morphological change, cell viability, LDH and Il-1ß release by cells,, and Hoechst/PI staining were used to detect the occurrence of pyroptosis. Realtime-PCR, western blot, immunofluorescence, and immunohistochemistry (IHC) were used to investigate the expressions of pyroptosis-related proteins. Datasets analyze showed the expressions of NLRP3, Caspase 1, ASC and GSDMD were all decreased in PCa comparing with normal tissues, but without prognostic significance. CVL treatment weakened the viabilities of PCa cells. Cell morphology changing, cytoplasmic vacuole formation, membrane integrity loss, LDH and IL-1ß release and PI positive cells increasing were observed. NLRP3, Caspase 1, ASC, GSDMD and N-GSDMD expressions were elevated after CVL treatment, accompanied by a tendency of NF-κB transferring into nucleus. In vivo, CVL inhibited the growth of subcutaneous transplanted tumor. IHC showed CVL increased the expressions of NLRP3, ASC, and GSDMD, and decreased the expression of Ki-67 in transplanted tumor tissues. CONCLUSION: This study demonstrated that CVL could induce pyroptosis in PCa cells through NLRP3-caspase1-ASC inflammasome by promoting nuclear translocation of NF-κB, which would lay a foundation for the application of adrenergic receptor antagonist in PCa.

Dual role of Nrf2/HO-1 pathway in Z-ligustilide-induced ferroptosis against AML cells.

BACKGROUND: The scarcity of drugs targeting AML cells poses a significant challenge in AML management. Z-Ligustilide (Z-LIG), a phthalide compound, shows promising pharmacological potential as a candidate for AML therapy. However, its precise selective mechanism remains unclear. PURPOSE: In order to assess the selective inducement effects of Z-LIG on ferroptosis in AML cells and explore the possible involvement of the Nrf2/HO-1 pathway in the regulation of ferroptosis. METHODS: Through in vitro cell proliferation and in vivo tumor growth tests, the evaluation of Z-LIG's anticancer activity was conducted. Ferroptosis was determined by the measurement of ROS and lipid peroxide levels using flow cytometry, as well as the observation of mitochondrial morphology. To analyze the iron-related factors, western blot analysis was employed. The up-regulation of the Nrf2/HO-1 axis was confirmed through various experimental techniques, including CRISPR/Cas9 gene knockout, fluorescent probe staining, and flow cytometry. The efficacy of Z-LIG in inducing ferroptosis was further validated in a xenograft nude mouse model. RESULTS: Our study revealed that Z-LIG specifically triggered lipid peroxidation-driven cell death in AML cells. Z-LIG downregulated the total protein and nuclear entrance levels of IRP2, resulting in upregulation of FTH1 and downregulation of TFR1. Z-LIG significantly increased the susceptibility to ferroptosis by upregulating ACSL4 levels and simultaneously suppressing the activity of GPX4. Notably, the Nrf2/HO-1 pathway displayed a twofold impact in the ferroptosis induced by Z-LIG. Mild activation suppressed ferroptosis, while excessive activation promoted it, mainly driven by ROS-induced labile iron pool (LIP) accumulation in AML cells, which was not observed in normal human cells. Additionally, Nrf2 knockout and HO-1 knockdown reversed iron imbalance and mitochondrial damage induced by Z-LIG in HL-60 cells. Z-LIG effectively inhibited the growth of AML xenografts in mice, and Nrf2 knockout partially weakened its antitumor effect by inhibiting ferroptosis. CONCLUSION: Our study presents biological proof indicating that the selective initiation of ferroptosis in leukemia cells is credited to the excessive activation of the Nrf2/HO-1 pathway triggered by Z-LIG.

CYLD regulates cell ferroptosis through Hippo/YAP signaling in prostate cancer progression.

Prostate cancer (PCa) is one of the most common malignancy in men. However, the molecular mechanism of its pathogenesis has not yet been elucidated. In this study, we demonstrated that CYLD, a novel deubiquitinating enzyme, impeded PCa development and progression via tumor suppression. First, we found that CYLD was downregulated in PCa tissues, and its expression was inversely correlated with pathological grade and clinical stage. Moreover, we discovered that CYLD inhibited tumor cell proliferation and enhanced the sensitivity to cell ferroptosis in PCa in vitro and in vivo, respectively. Mechanistically, we demonstrated that CYLD suppressed the ubiquitination of YAP protein, then promoted ACSL4 and TFRC mRNA transcription. Then, we demonstrated that CYLD could enhance the sensitivity of PCa xenografts to ferroptosis in vivo. Furthermore, we discovered for the first time that there was a positive correlation between CYLD expression and ACSL4 or TFRC expression in human PCa specimens. The results of this study suggested that CYLD acted as a tumor suppressor gene in PCa and promoted cell ferroptosis through Hippo/YAP signaling.

Uncovering the substituted-position effect on excited-state evolution of benzophenone-phenothiazine dyads.

Photofunctional materials based on donor-acceptor molecules have drawn intense attention due to their unique optical properties. Importantly, Systematic investigation of substitution effects on excited-state charge transfer dynamics of donor-acceptor molecules is a powerful approach for identifying application-relevant design principles. Here, by coupling phenothiazine (PTZ) at the ortho-, meta-, and para-positions of the benzene ring of benzophenone (BP), three regioisomeric BP-PTZ dyads were designed to understand the relationship between substituted positions and excited-state evolution channels. Ultrafast transient absorption is used to detect and trace the transient species and related evolution channels of BP-PTZ dyads at excited state. In a non-polar solvent, BP-o-PTZ undergoes the through-space charge transfer process to produce a singlet charge-transfer (1CT) state, which subsequently proceeds the intersystem crossing process and transforms into a triplet charge-transfer (3CT) state; BP-m-PTZ experiences intramolecular charge transfer (ICT) process to generate the 1CT state, which subsequently transforms into the 3CT state by the intersystem crossing (ISC) and finally converts into the local-excited triplet (3LE) state; as for BP-p-PTZ, only 3LE states can be detected after the ISC process from the 1CT state. On the other hand, the twisted ICT states are generated via twisted motion between the donor and acceptor for all BP-PTZ dyads or planarization of the PTZ unit in high polar solvents. The excited-state theoretical calculations unveil that the features of ICT and intramolecular interaction between the three dyads play a decisive role in determining the through-bond charge transfer and through-space charge transfer processes. Also, these results demonstrate that the excited-state evolution channels of PTZ derivatives could be modified by tuning the substituted positions of the donor-acceptor dyads. This study provides a deep perspective for the substitute-position effect on donor-acceptor-type PTZ derivatives.

Discovery of novel flavonoid-based CDK9 degraders for prostate cancer treatment via a PROTAC strategy.

CDK9 plays a vital role in regulating RNA transcription and significantly impacts the expression of short-lived proteins such as Mcl-1 and c-Myc. Thus, targeting CDK9 holds great promise for the development of antitumor drugs. Natural flavonoid derivatives have recently gained considerable attention in the field of antitumor drug research due to their broad bioactivity and low toxicity. In this study, the PROTAC strategy was used to perform structural modifications of the flavonoid derivative LWT-111 to design a series of flavonoid-based CDK9 degraders. Notably, compound CP-07 emerged as a potent CDK9 degrader, effectively suppressing the proliferation and colony formation of 22RV1 cells by downregulating Mcl-1 and c-Myc. Moreover, CP-07 exhibited significant tumor growth inhibition with a TGI of 75.1% when administered at a dose of 20 mg/kg in the 22RV1 xenograft tumor model. These findings demonstrated the potential of CP-07 as a powerful flavonoid-based CDK9 degrader for prostate cancer therapy.

SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells.

The cystine transporter solute carrier family 7 member 11 (SLC7A11; also called xCT) protects cancer cells from oxidative stress and is overexpressed in many cancers. Here we report a surprising finding that, whereas moderate overexpression of SLC7A11 is beneficial for cancer cells treated with H2O2, a common oxidative stress inducer, its high overexpression dramatically increases H2O2-induced cell death. Mechanistically, high cystine uptake in cancer cells with high overexpression of SLC7A11 in combination with H2O2 treatment results in toxic buildup of intracellular cystine and other disulfide molecules, NADPH depletion, redox system collapse, and rapid cell death (likely disulfidptosis). We further show that high overexpression of SLC7A11 promotes tumor growth but suppresses tumor metastasis, likely because metastasizing cancer cells with high expression of SLC7A11 are particularly susceptible to oxidative stress. Our findings reveal that SLC7A11 expression level dictates cancer cells' sensitivity to oxidative stress and suggests a context-dependent role for SLC7A11 in tumor biology.

Case report: Endoscopic frontal sinus opening surgery for noninflammatory frontal sinus headache: A short case series.

Objective: The objectives of this study were to analyze rhinogenic headache, i.e., noninflammatory frontal sinus headache, a headache caused by bony obstruction of the frontal sinus drainage channels that receives relatively insufficient attention clinically, and to propose endoscopic frontal sinus opening surgery as a treatment based on the etiology. Study Design: Case series. Setting: From the data of patients with noninflammatory frontal sinus headache who underwent endoscopic frontal sinus surgery in Hospital of Chengdu University of Traditional Chinese Medicine during 2016-2021, data for three cases with detailed postoperative follow-up data were extracted for case series reports. Methods: This report provides detailed information on three patients with noninflammatory frontal sinusitis headache. Treatment options include surgery and rechecking, with the visual analogue scale (VAS) scores of preoperative and postoperative symptoms, CT, and endoscopic images. Three patients had common characteristics: the clinical manifestations were recurrent or persistent with pain and discomfort in the forehead area, but there was no nasal obstruction or runny nose; the paranasal sinus CT revealed no signs of inflammation in the sinuses but suggested bony obstruction of the drainage channel of the frontal sinus. Results: All three patients had recovery from headache, nasal mucosal recovery, and patent frontal sinus drainage. The recurrence rate of forehead tightness and discomfort or pain was 0. Conclusion: Noninflammatory frontal sinus headache does exist. Endoscopic frontal sinus opening surgery is a feasible treatment modality that can largely or even completely eliminate the stuffy swelling and pain in the forehead. The diagnosis and surgical indications for this disease are based on a combination of anatomical abnormalities and clinical symptoms.

Simultaneous nitrogen removal via heterotrophic nitrification and aerobic denitrification by a novel Lysinibacillus fusiformis B301.

Simultaneous nitrogen removal via heterotrophic nitrification and aerobic denitrification (HN-AD) has received widespread attention in biological treatment of wastewater. This study reported a novel Lysinibacillus fusiformis B301 strain, which effectively removed nitrogenous pollutants via HN-AD in one aerobic reactor with no nitrite accumulated. It exhibited the optimal nitrogen removal efficiency under 30°C, citrate as the carbon source and C/N ratio of 15. The maximum nitrogen removal rates were up to 2.11 mgNH4 + -N/(L·h), 1.62 mgNO3 - -N/(L·h), and 1.41 mgNO2 - -N/(L·h), respectively, when ammonium, nitrate, and nitrite were employed as the only nitrogen source under aerobic conditions. Ammonium nitrogen was preferentially consumed via HN-AD in the coexistence of three nitrogen species, and the removal efficiencies of total nitrogen were up to 94.26%. Nitrogen balance analysis suggested that 83.25% of ammonium was converted to gaseous nitrogen. The HD-AD pathway catalyzed by L. fusiformis B301 followed NH 4 + → N H 2 OH → NO 2 - → NO 3 - → NO 2 - → N 2 , supported by the results of key denitrifying enzymatic activities. PRACTITIONER POINTS: The novel Lysinibacillus fusiformis B301 exhibited the outstanding HN-AD ability. The novel Lysinibacillus fusiformis B301 simultaneously removed multiple nitrogen species. No nitrite accumulated during the HN-AD process. Five key denitrifying enzymes were involved in the HN-AD process. Ammonium nitrogen (83.25%) was converted to gaseous nitrogen by the novel strain.

Sympathetic ß2-adrenergic receptor blockade overcomes docetaxel resistance in prostate cancer.

PURPOSE: Due to the limited effective therapies, resistance to docetaxel is ordinarily fatal and remains a critical clinical challenge.ß2-adrenergic receptor(ß2-AR)can promote the metastasis and invasion of prostate cancer, but the role in chemotherapy-resistant prostate cancer remains unclear. METHODS: By downloading the GEO database in NCBI, the expression of ß2-AR in different prostate tissues was analyzed. We constructed docetaxel-resistant prostate cancer cell lines by the method of dose-escalation. LC3B-labeled stable cells and shAtg5 knockdown stable cells were constructed by lentivirus infection. The molecular mechanism of ß2-AR affecting docetaxel sensitivity through apoptosis and autophage were investigated by flow cytometry, mitochondrial membrane potential and western blot. Then we detected the interaction between autophagy and apoptotic by performing immunoprecipitation assay. RESULTS: We show that restraining the activity of ß2-AR sensitized the cell response and reduced the resistance to docetaxel. The mechanism involves the regulation of ß2-AR in the cellular response to docetaxel through apoptosis and autophagy via caspase signaling and Atg5/AMPK/mTOR pathway as well as the effect of ß2-AR on the crosstalk between apoptosis and autophagy via p38 MAPK and JNK/c-Jun/FOXO3a signaling pathways. CONCLUSION: Our data demonstrate that ß2-AR inhibitor-induced autophagy and apoptosis contribute to the effectiveness responses to docetaxel in castration-resistant prostate cancer, and in combination with pharmacological agents of ß2-AR and autophagy inhibitors may provide a potential therapeutic strategy to enhance the limited capacity of docetaxel to control castration-resistant prostate cancer.

Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis.

SLC7A11-mediated cystine uptake suppresses ferroptosis yet promotes cell death under glucose starvation; the nature of the latter cell death remains unknown. Here we show that aberrant accumulation of intracellular disulfides in SLC7A11high cells under glucose starvation induces a previously uncharacterized form of cell death distinct from apoptosis and ferroptosis. We term this cell death disulfidptosis. Chemical proteomics and cell biological analyses showed that glucose starvation in SLC7A11high cells induces aberrant disulfide bonds in actin cytoskeleton proteins and F-actin collapse in a SLC7A11-dependent manner. CRISPR screens and functional studies revealed that inactivation of the WAVE regulatory complex (which promotes actin polymerization and lamellipodia formation) suppresses disulfidptosis, whereas constitutive activation of Rac promotes disulfidptosis. We further show that glucose transporter inhibitors induce disulfidptosis in SLC7A11high cancer cells and suppress SLC7A11high tumour growth. Our results reveal that the susceptibility of the actin cytoskeleton to disulfide stress mediates disulfidptosis and suggest a therapeutic strategy to target disulfidptosis in cancer treatment.

Hyperglycaemia in pregnancy and offspring blood pressure: a systematic review and meta-analysis.

BACKGROUND: Hyperglycemia in pregnancy (HIP) is suggested to be a risk factor for elevated blood pressure (BP) in offspring. However, the empirical evidence was mixed. Thus, this systematic review and meta-analysis was conducted to synthesize current evidence assessing the association between HIP and BP in offspring. METHODS: We searched PubMed, MEDLINE, and Embase to identify articles published from inception until 9 February 2021. A random-effects meta-analysis was performed to calculate a pooled effect size and 95% confidence interval (CI). Furthermore, the effects were evaluated separately while grouping by the offspring's sex, region, economic level, published year, insulin treatment status, and BP measurement. Each article was independently reviewed for quality. RESULTS: Of 3385 citations identified, 23 studies involving 88695 offspring were included. The study found that the offspring of women with HIP had an increased level of both systolic blood pressure (SBP; mean difference 1.90, 95% CI 1.09 to 2.70 mmHg, P < 0.001) and diastolic blood pressure (DBP; mean difference 0.87 mmHg, 95% CI 0.11 to 1.17 mmHg, P = 0.02) compared with those whose mothers with normal blood glucose during pregnancy. According to subgroup analyses, gestational diabetes mellitus (GDM) appeared to have varied impacts on offspring BP by sex of offspring, region and economic level of family, published year, maternal insulin treatment status, and BP measurement. CONCLUSION: Current evidence showed that HIP was associated with an elevated BP in offspring. Prenatal interventions targated on reducing HIP might be beneficial for controlling for offspring BP.

Risk assessment and validation of farmland abandonment based on time series change detection.

Farmland abandonment, a widespread phenomenon during land-use transition, leads to a cycling or vanishing evolution of farmland resources. As urbanization advances, an increasing number of agricultural laborers migrate from rural to urban areas, causing ongoing farmland abandonment. However, in contrast to the abandoned information extraction and driving mechanisms revelation, the potential risk of farmland abandonment has received insufficient attention. This study took Yangtze River Economic Belt of China as study area, selected multiple aspects to construct a risk assessment system for farmland abandonment, and applied time series change detection to verify the results. The results showed that (1) farmland abandonment risk, with a regional average value of 0.0978, has strong spatial heterogeneity, with high values clustering in Yunnan-Guizhou and Sichuan-Chongqing mountainous areas and low values distributed in the midstream and downstream plains and the Sichuan Basin. (2) The proportion of farmland area gradually decreased as the risk grade increased. Farmland, with low abandonment risk, occupied an area of 204,837 km2, constituting the highest percentage of 35.18% among the overall farmland, and was mainly distributed in the provinces of Jiangsu and Anhui. The area of farmland with high risk was 16,458 km2, only accounting for 2.83%, the majority of which was clustered in Sichuan and Yunnan provinces. (3) The Normalized Difference Vegetation Index (NDVI) time series change detection validated the reliability of the risk assessment system. Samples of farmland having low abandonment risk indeed had the lowest abandonment rate of 10%, and those which indicated high risk had the highest abandonment rate of 32%. We propose differentiated managements for farmland resources with high and low abandonment risk from the perspective of sustainable use. This study provides a more reasonable and scientific system for farmland abandonment risk assessment and helps to fill the research gap.

A ferroptosis defense mechanism mediated by glycerol-3-phosphate dehydrogenase 2 in mitochondria.

Mechanisms of defense against ferroptosis (an iron-dependent form of cell death induced by lipid peroxidation) in cellular organelles remain poorly understood, hindering our ability to target ferroptosis in disease treatment. In this study, metabolomic analyses revealed that treatment of cancer cells with glutathione peroxidase 4 (GPX4) inhibitors results in intracellular glycerol-3-phosphate (G3P) depletion. We further showed that supplementation of cancer cells with G3P attenuates ferroptosis induced by GPX4 inhibitors in a G3P dehydrogenase 2 (GPD2)-dependent manner; GPD2 deletion sensitizes cancer cells to GPX4 inhibition-induced mitochondrial lipid peroxidation and ferroptosis, and combined deletion of GPX4 and GPD2 synergistically suppresses tumor growth by inducing ferroptosis in vivo. Mechanistically, inner mitochondrial membrane-localized GPD2 couples G3P oxidation with ubiquinone reduction to ubiquinol, which acts as a radical-trapping antioxidant to suppress ferroptosis in mitochondria. Taken together, these results reveal that GPD2 participates in ferroptosis defense in mitochondria by generating ubiquinol.