Iridium(III) carbene complexes as potent girdin inhibitors against metastatic cancers.

Many cancer-driving protein targets remain undruggable due to a lack of binding molecular scaffolds. In this regard, octahedral metal complexes with unique and versatile three-dimensional structures have rarely been explored as inhibitors of undruggable protein targets. Here, we describe antitumor iridium(III) pyridinium-N-heterocyclic carbene complex 1a, which profoundly reduces the viability of lung and breast cancer cells as well as cancer patient-derived organoids at low micromolar concentrations. Compound 1a effectively inhibits the growth of non-small-cell lung cancer and triple-negative breast cancer xenograft tumors, impedes the metastatic spread of breast cancer cells, and can be modified into an antibody-drug conjugate payload to achieve precise tumor delivery in mice. Identified by thermal proteome profiling, an important molecular target of 1a in cellulo is Girdin, a multifunctional adaptor protein that is overexpressed in cancer cells and unequivocally serves as a signaling hub for multiple pivotal oncogenic pathways. However, specific small-molecule inhibitors of Girdin have not yet been developed. Notably, 1a exhibits high binding affinity to Girdin with a Kd of 1.3 µM and targets the Girdin-linked EGFR/AKT/mTOR/STAT3 cancer-driving pathway, inhibiting cancer cell proliferation and metastatic activity. Our study reveals a potent Girdin-targeting anticancer compound and demonstrates that octahedral metal complexes constitute an untapped library of small-molecule inhibitors that can fit into the ligand-binding pockets of key oncoproteins.

Easy but Efficient: Facile Approach to Molecule with Theoretically Justified Donor-Acceptor Structure for Effective Photothermal Conversion and Intravenous Photothermal Therapy.

To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof-of-concept, hereby a conventional strategy is presented to prepare donor-acceptor (D-A) structured PTAs through cycloaddition-retroelectrocyclization (CA-RE) reaction, and the resultant PTAs give high PCE upon near-infrared (NIR) irradiation. By joint experimental-theoretical study, these PTAs exhibit prominent D-A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA-TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760-nm LED lamp (1.2 W cm-2). In vitro and in vivo experimental results revealed that DMA-TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA-RE reaction as a convenient approach to obtain twisted D-A structured PTAs for effective PTT and probably promote the progress of cancer therapies.

Cycloplatinated (II) Complex Based on Isoquinoline Alkaloid Elicits Ferritinophagy-Dependent Ferroptosis in Triple-Negative Breast Cancer Cells.

The development and optimization of metal-based anticancer drugs with novel cytotoxic mechanisms have emerged as key strategies to overcome chemotherapeutic resistance and side effects. Agents that simultaneously induce ferroptosis and autophagic death have received extensive attention as potential modalities for cancer therapy. However, only a limited set of drugs or treatment modalities can synergistically induce ferroptosis and autophagic tumor cell death. In this work, we designed and synthesized four new cycloplatinated (II) complexes harboring an isoquinoline alkaloid C∧N ligand. On screening the in vitro activity of these agents, we found that Pt-3 exhibited greater selectivity of cytotoxicity, decreased resistance factors, and improved anticancer activity compared to cisplatin. Furthermore, Pt-3, which we demonstrate can initiate potent ferritinophagy-dependent ferroptosis, exhibits less toxic and better therapeutic activity than cisplatin in vivo. Our results identify Pt-3 as a promising candidate or paradigm for further drug development in cancer treatment.

The leaching behavior of hazardous element under different leaching procedure utilizing slag-fly ash-based agent: Chromium, antimony, and lead.

Low-carbon cementitious materials based on blast furnace slag (BFS) and municipal solid waste incineration (MSWI) fly ash play a pivotal role in the construction industry by substituting cement clinker. This innovation significantly reduces CO2 emissions and enables the extensive utilization of both industrial solid waste and hazardous urban waste on a large scale. However, the application of MSWI fly ash as a precursor for alkali-activated cementitious materials presents a significant leaching risk of heavy metal during the extended reaction process, posing a critical barrier to the efficient and widespread utilization of these solid waste. Three static leaching methods [horizontal vibration (HV), sulphuric acid & nitric acid (SN), and acetic acid buffer solution (AAB)], along with acid neutralization capacity (ANC) leaching tests, were applied in BFS-fly ash-based cementitious materials (BFCM) to assess the leaching behavior of high-risk elements-Cr, Sb, and Pb-within MSWI fly ash. The A4 matrix (BFS: MSWI fly ash:FGDG = 70:20:10) exhibits a compressive strength of 72.51 MPa at 180 day, with the leaching concentrations of target elements remaining below the standard limit under chemical attack (H+ and OH-). The critical pH determined is 9.2 from the ANC leaching test results. Visual MINTEQ simulation illustrates the occurrence states of Cr, Sb, and Pb as (CrO4)2-, [Sb(OH)6]-, and Pb(OH)3- within the BFCM system, respectively. The "double salt effect", intended to enhance the dissociation degree of BFS, acts as the driving force behind the long-term hydration reaction. It also serves as an assurance in controlling the long-term leaching risk of object elements. The dissociation degree of BFS within A4 matrix increased by 38.71 %, with the relative content of the typical low-solubility double salt "Ettringite" reaching 29 % at 180 d. This study provides novel theoretical and data-driven evidence to investigate the leaching behavior associated with MSWI fly ash and the accomplishment of replacing cement clinker with low-carbon BFCM.

A review of solid wastes-based stabilizers for remediating heavy metals co-contaminated soil: Applications and challenges.

The remediation of heavy metals/metalloids (HMs) co-contaminated soil by solid wastes-based stabilizers (SWBS) has received major concern recently. Based on the literature reported in the latest years (2010-2023), this review systematically summarizes the different types of solid wastes (e.g., steel slag, coal fly ash, red mud, and sewage sludge, etc.) employed to stabilize HMs contaminated soil, and presents results from laboratory and field experiments. Firstly, the suitable solid wastes for soil remediation are reviewed, and the pros and cons are presented. Thereafter, the technical feasibility and economic benefit are evaluated for field application. Moreover, evaluation methods for remediation of different types of HMs-contaminated soil and the effects of SWBS on soil properties are summarized. Finally, due to the large specific surface, porous structure, and high reactivity, the SWBS can effectively stabilize HMs via adsorption, complexation, co/precipitation, ion exchange, electrostatic interaction, redox, and hydration process. Importantly, the environmental implications and long-term effectiveness associated with the utilization of solid wastes are highlighted, which are challenges for practical implementation of soil stabilization using SWBS, because the aging of soil/solid wastes has not been thoroughly investigated. Future attention should focus on modifying the SWBS and establishing an integrated long-term stability evaluation method.

Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency in neonates. We designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of neonates. METHODS: Using the 16S ribosomal DNA (rDNA) sequencing method, we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates: patients undergoing jejunostomy to treat NEC (NP group), neonates undergoing jejunostomy to treat other conditions (NN group), and neonates with NEC undergoing conservative treatment (NC group). We took intestinal feces and saliva samples from patients at different time points. RESULTS: The beta diversities of the NP, NN, and NC groups were all similar. When comparing the beta diversities between different time points in the NP group, we found similar beta diversities at time points E1 to E3 but significant differences between the E2-E3 and E4 time points: the abundances of Klebsiella and Enterococcus (Proteobacteria) were higher at the E1-E3 time points; the abundance of Escherichia-Shigella (Proteobacteria) increased at the E2 time point, and the abundance of Klebsiella decreased significantly, whereas that of Streptococcus increased significantly at the E4 time point. CONCLUSIONS: Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small intestine. The sources of microbiota in the small intestine of neonates, especially in premature infants, may be affected by multiple factors.

Programmed cell death 10 can be used as a potential biomarker for ankylosing spondylitis diagnosis and treatment.

STUDY DESIGN: Diagnostic study. OBJECTIVE: Programmed cell death 10 (PDCD10) is a new versatile molecule involved in signal transduction regulation in angiogenesis and tumors. The potential of using it as a biomarker for the diagnosis of ankylosing spondylitis (AS) is still unknown. SETTING: University laboratory in Gannan Medical University, China. METHODS: Expression of PDCD10 was analyzed using clinical samples of patients with AS and Gene Expression Omnibus (GEO) data GDS5231. To explore its function, PDCD10 was upregulated and downregulated in synovial cells. Spearman analysis was used to study the association between PDCD10 and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The Receiver operating characteristic (ROC) curve was applied to evaluate the sensitivity and specificity of PDCD10. RESULTS: Expression of PDCD10 was upregulated in patients with AS and it is capable of promoting the calcification of synovial cells. A positive association between PDCD10 and the BASDAI and the mSASSS was observed. The area under the ROC curve (AUC) of PDCD10 was 82% with a 95% confidence interval of [0.772, 0.868]. CONCLUSIONS: PDCD10 is upregulated in patients with AS and it can promote the calcification of synovial cells in vitro. PDCD10 is positively associated with outcome parameters of AS. ROC analysis of PDCD10 suggests that it can be used as a biomarker for the diagnosis and treatment of AS.

Medial Septal Glutamatergic Neurons Modulate States of Consciousness during Sevoflurane Anesthesia in Mice.

BACKGROUND: Multiple neural structures involved in maintaining wakefulness have been found to promote arousal from general anesthesia. The medial septum is a critical region that modulates arousal behavior. This study hypothesized that glutamatergic neurons in the medial septum play a crucial role in regulating states of consciousness during sevoflurane general anesthesia. METHODS: Adult male mice were used in this study. The effects of sevoflurane anesthesia on neuronal activity were determined by fiber photometry. Lesions and chemogenetic manipulations were used to study the effects of the altered activity of medial septal glutamatergic neurons on anesthesia induction, emergence, and sensitivity to sevoflurane. Optogenetic stimulation was used to observe the role of acute activation of medial septal glutamatergic neurons on cortical activity and behavioral changes during sevoflurane-induced continuous steady state of general anesthesia and burst suppression state. RESULTS: The authors found that medial septal glutamatergic neuronal activity decreased during sevoflurane anesthesia induction and recovered in the early period of emergence. Chemogenetic activation of medial septal glutamatergic neurons prolonged the induction time (mean ± SD, hM3Dq-clozapine N-oxide vs. hM3Dq-saline, 297.5 ± 60.1 s vs. 229.4 ± 29.9 s, P < 0.001, n = 11) and decreased the emergence time (53.2 ± 11.8 s vs. 77.5 ± 33.5 s, P = 0.025, n = 11). Lesions or chemogenetic inhibition of these neurons produced the opposite effects. During steady state of general anesthesia and deep anesthesia-induced burst suppression state, acute optogenetic activation of medial septal glutamatergic neurons induced cortical activation and behavioral emergence. CONCLUSIONS: The study findings reveal that activation of medial septal glutamatergic neurons has arousal-promoting effects during sevoflurane anesthesia in male mice. The activation of these neurons prolongs the induction and accelerates the emergence of anesthesia.

Molecular-Assisted Breeding of Cadmium Pollution-Safe Cultivars.

Cadmium (Cd) contamination in edible agricultural products, especially in crops intended for consumption, has raised worldwide concerns regarding food safety. Breeding of Cd pollution-safe cultivars (Cd-PSCs) is an effective solution to preventing the entry of Cd into the food chain from contaminated agricultural soil. Molecular-assisted breeding methods, based on molecular mechanisms for cultivar-dependent Cd accumulation and bioinformatic tools, have been developed to accelerate and facilitate the breeding of Cd-PSCs. This review summarizes the recent progress in the research of the low Cd accumulation traits of Cd-PSCs in different crops. Furthermore, the application of molecular-assisted breeding methods, including transgenic approaches, genome editing, marker-assisted selection, whole genome-wide association analysis, and transcriptome, has been highlighted to outline the breeding of Cd-PSCs by identifying critical genes and molecular biomarkers. This review provides a comprehensive overview of the development of Cd-PSCs and the potential future for breeding Cd-PSC using modern molecular technologies.

Prognostic Value of Venous Outflow Profiles on Multiphase CT Angiography for the Patients with Acute Ischemic Stroke After Endovascular Thrombectomy.

To evaluate the prognostic value of venous outflow (VO) profiles evaluated on multiphase CTA (mCTA) for the patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). We retrospectively collected 150 patients with AIS who underwent pre-treatment CT perfusion (CTP) evaluation and subsequent EVT from April 2018 to April 2022. Three-phases (peak arterial phase, peak venous phase, late venous phase) CTA was reconstructed from CTP raw data, and VO was evaluated on three-phases CTA, respectively. Favorable VO was regarded as a cortical vein opacification score of 3-6, and unfavorable VO as a score of 0-2. Good outcome was defined as modified Rankin Scale score of 0-2 at 90 days after EVT. Multivariate logistic regression analysis was performed to explore the predictors of good outcome. Prognostic value was assessed and compared using receiver operating characteristic (ROC) curves and Delong test. We found that good outcome was achieved in 85 (56.7%) patients. Among the mCTA-derived VO profiles, only favorable peak venous phase VO was found to be independently associated with good outcome (P < 0.001). After integrating favorable peak venous phase VO with lower post-treatment National Institute of Health Stroke Scale score at 24 hours, successful recanalization and favorable hypoperfusion intensity ratio, the predictive ability for a good outcome was significantly improved than before (area under the ROC curve; 0.947 vs 0.881; P = 0.002). This study supports that favorable peak venous VO profiles on mCTA might be a promising biomarker in predicting the good outcome in patients with AIS after EVT.

Circular RNAs in osteosarcoma: An update of recent studies (Review).

Osteosarcoma (OS) prevailing in children and adolescents mainly occurs at the metaphysis of long bones. As it is associated with a high invasive and metastatic ability, resistance to chemotherapy, and a low 5­year survival rate, the diagnosis and treatment of OS post a global healthy issue. Over the past decades, RNA biology has shed new light onto the pathogenesis of OS. As a type of non­coding RNAs, circular RNAs (circRNAs) have been found to play crucial roles in cellular activities. Recently, a large number of circRNAs have been identified in OS and some of them have been validated to be functional in OS. In the present review, abnormally expressed and different types of circRNAs in OS are summarized. Functional studies on circRNAs have revealed that circRNAs can regulate gene expression at different levels, such as gene transcription, precursor mRNA splicing, miRNA sponges and translation into proteins/peptides. Mechanistic analyses on circRNAs show that circRNAs can regulate JAK­STAT3, NF­κB, PI3K­AKT, Wnt/ß­catenin signaling pathways during the occurrence and development of OS. Furthermore, the potential clinical applications of circRNAs are also emphasized. The present review focus on the current knowledge on the functions and mechanisms of circRNAs in the pathogenesis of OS, aiming to provide new insight into the OS diagnosis and treatment of OS.

Hand grip strength is inversely associated with total daily insulin dose requirement in patients with type 2 diabetes mellitus: a cross-sectional study.

Background: Short-term (2 weeks to 3 months) insulin intensive therapy using continuous subcutaneous insulin infusion (CSII) can improve islet beta cell function and prolong glycemic remission in patients with newly diagnosed type 2 diabetes mellitus (T2DM). However, the total daily insulin dose (TDD, IU/kg/d) required to achieve near-normoglycemic control with CSII still needs to be frequently adjusted based on blood glucose monitoring. Although real-time continuous glucose monitoring (rtCGM), which measures the interstitial fluid glucose concentration continuously without much difficulty, facilitates the adjustment of insulin dosage, its adoption in the T2DM population is strictly limited by insurance coverage and lack of awareness of rtCGM among clinicians. Thus, it is of clinical significance to identify easy-to-use parameters that may allow a more rapid and accurate prediction of TDD requirement. This study aimed to explore the association between hand grip strength (HGS) and TDD requirement in patients with T2DM receiving CSII therapy. Methods: A total of 180 eligible patients with T2DM were enrolled in the study and divided into three groups based on their HGS: low (L), medium (M), and high (H). The TDD requirement was calculated on day 7 or 8 of CSII treatment. Anthropometric parameters, including HGS, skeletal muscle mass, skeletal muscle index (SMI) and 6-m gait speed, and laboratory data, were collected on the morning of the second day after admission, within the first 24 h of CSII therapy. These parameters were used to identify significant predictors of TDD requirement using Pearson or Spearman correlation test, and stepwise multiple regression analysis. Results: There were no significant differences in age, duration of T2DM, waist-to-hip ratio (WHR), body mass index (BMI), blood pressure, liver function, estimated glomerular filtration rate, triglyceride, total cholesterol, glycosylated hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of beta cell function (HOMA-ß) among the groups. The H group had higher body muscle mass-to-fat ratio (BMFR), skeletal muscle mass-to-fat ratio (SMFR), SMI, 6-m gait speed, and lower TDD requirement than the M and L groups. The HGS negatively correlated with TDD requirement (r = -0.33, p < 0.001) after adjusting for sex, age, BMI, WHR, HbA1c, Ln (HOMA-ß), Ln (HOMA-IR), Ln (BMFR), Ln (SMFR), SMI, and 6-m gait speed. Multivariate stepwise regression analysis indicated that HGS was an independent predictor of TDD requirement in patients with T2DM (ß = -0.45, p < 0 001). Conclusion: Lower HGS is associated with an increased TDD requirement in T2DM patients. HGS may facilitate the prediction of TDD requirement in T2DM patients receiving CSII therapy.

[Potential components and mechanism of Liangxue Tuezi Mixture in treating Henoch-Schönlein purpura based on network pharmacology and metabolomics].

Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.

Rapid detection of urine chloride enabled by ion exchange in hydrophilic lead halide perovskite nanocrystals.

The rapid and precise detection of chloride ions in biosystems is of great importance for clinical diagnosis. In this work, hydrophilic CsPbBr3 perovskite nanocrystals (PNCs) with a high photoluminescence (PL) quantum yield (QY) of 59% (0.5 g L-1) are successfully achieved through the passivation of micellar glycyrrhizic acid (GA), which enables good dispersion of PNCs in ethanol. Due to the ionic nature and halogen-dominated band edge, PNCs exhibit fast ion-exchange and halogen-dependent optical properties. As a result, colloidal GA-capped PNC ethanol solution shows a continuous PL shift once aqueous Cl- with different concentrations is added. This fluorescence sensor shows a wide linear detection range (2-200 mM) of Cl-, short response time (∼1 s), and low limit of detection (1.82 mM). Because of the encapsulation of GA, good water and pH stability, and anti-interference performance are observed for the GA-capped PNC-based fluorescence sensor. Our findings provide an insight into the biosensor applications of hydrophilic PNCs.

Cytotoxic cis-ruthenium(III) bis(amidine) complexes.

In chemotherapy, the search for ruthenium compounds as alternatives to platinum compounds is proposed because of their unique properties. However, the geometry effect of ruthenium complexes is sparely investigated. In this paper, we report the synthesis of a series of bis(acetylacetonato)ruthenium(III) complexes bearing two amidines (1-) in a cis configuration. These complexes are highly cytotoxic against various cancer cell lines, including a cisplatin-resistant cell line. In vitro studies suggested that the representative complex can induce cell cycle G0/G1 phase arrest, decrease the mitochondrial membrane potential, elevate the intracellular reactive oxygen species level, and cause DNA damage and caspase-mediated mitochondrial pathway apoptosis in NCI-H460 cells. In vivo, it can effectively inhibit tumor xenograft growth in nude mouse models with no body weight loss. In combination with the reported trans-bis(amidine)ruthenium(III) complexes, we found that ruthenium(III) bis(amidine) complexes could be cytotoxic in both trans and cis geometries, which is in contrast to platinum-based compounds.

The Preparation Process and Hydration Mechanism of Steel Slag-Based Ultra-Fine Tailing Cementitious Filler.

Steel slag, desulphurised ash, desulphurised gypsum and ultra-fine iron tailing sand are common industrial solid wastes with low utilisation rates. Herein, industrial solid wastes (steel slag, desulphurised gypsum and desulphurised ash) were used as the main raw materials to prepare a gelling material and ultra-fine tailing was used as an aggregate to prepare a new type of cementing filler for mine filling. The optimal composition of the cementing filler was 75% steel slag, 16.5% desulphurised gypsum, 8.75% desulphurised ash, 1:4 binders and tailing mass ration and 70% concentration. The compressive strength of the 28-day sample reached 1.24 MPa, meeting the mine-filling requirements, while that of the 90-day sample was 3.16 MPa. The microscopic analysis results showed that a small amount of C3A reacted with the sulphate in the desulphurised gypsum to form ettringite at the early stage of hydration after the steel slag was activated by the desulphurisation by-products. In addition, C2S produced hydrated calcium silicate gel in an alkaline environment. As hydration proceeded, the sulphite in the desulphurised ash was converted to provide sulphate for the later sustained reaction. Under the long-term joint action of alkali and sulphate, the reactive silica-oxygen tetrahedra and alumina-oxygen tetrahedra depolymerised and then polymerised, further promoting the hydration reaction to generate hydrated calcium silicate gel and ettringite. The low-carbon and low-cost filler studied in this paper represents a new methodology for the synergistic utilisation of multiple forms of solid waste.

Integration of Non-targeted Proteomics Mass Spectrometry with Machine Learning for Screening Cooked Beef Adulterated Samples.

The degradation of ingredients in heat-processed meat products makes their authentication challenging. In this study, protein profiles of raw beef, chicken, duck, pork, and binary simulated adulterated beef samples (chicken-beef, duck-beef, and pork-beef) and their heat-processed samples were obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Heat-stable characteristic proteins were found by screening the overlapping characteristic protein ion peaks of the raw and corresponding heat-processed samples, which were discovered by partial least-squares discriminant analysis. Based on the 36 heat-stable characteristic proteins, qualitative classification for the raw and heat-processed meats was achieved by extreme gradient boosting. Moreover, quantitative analysis via partial least squares regression was applied to determine the adulteration ratio of the simulated adulterated beef samples. The validity of the approach was confirmed by a blind test with the mean accuracy of 97.4%. The limit of detection and limit of quantification of this method were determined to be 5 and 8%, respectively, showing its practical aspect for the beef authentication.

The role of stimulator of interferon genes-mediated AMPK/mTOR/P70S6K autophagy pathway in cyfluthrin-induced testicular injury.

Cyfluthrin is widely used in the field of sanitary pest control by its wide insecticidal spectrum, high efficiency and low toxicity, low residue, and good biodegradability. But, as a double-edged sword, a large amount of cyfluthrin remains are still in the environment. The residual cyfluthrin is absorbed into the food chain through vegetation and then poses a risk to soil organisms and human health. Several studies have suggested that cyfluthrin is one of the main factors causing testicular damage, but the mechanism remains unclear. In this study, we established in vivo and in vitro models of testicular injury in rats and GC-2 cells exposed to cyfluthrin to explore whether stimulator of interferon genes (STING) gene mediates the regulation of AMPK/mTOR/p70S6K autophagy pathway, which lays a foundation for further study of the mechanism of testicular injury induced by cyfluthrin. The results showed that the activity of super oxide dismutase in testis decreased and the activity of malonic dialdehyde increased with the increase of concentration in vivo and in vitro. At the same time, the levels of mitochondrial damage and inflammation in the testis also increased, which further activated autophagy. In this process, the increased level of inflammation is related to the increased expression of STING gene, and AMPK/mTOR/p70S6K autophagy pathway is also involved. To sum up, cyfluthrin has certain reproductive toxicity, and long-term exposure can induce testicular cell damage. STING gene can participate in cyfluthrin-induced testicular injury through AMPK/mTOR/P70S6K autophagy pathway.