Application of combined ablation and immunotherapy in NSCLC and liver cancer: Current status and future prospects.

This review examines combining tumor ablation therapy with immunotherapy for respiratory and digestive system tumors, particularly NSCLC and liver cancer. Despite advancements in traditional methods, they face limitations in advanced-stage tumors. Ablation techniques like RFA, MWA, and cryoablation offer minimally invasive options, while immune checkpoint inhibitors enhance the immune system's tumor-fighting ability. This review highlights their synergistic effects, clinical outcomes, and future research directions, including optimizing protocols, exploring new combinations, uncovering molecular mechanisms, advancing precision medicine, and improving accessibility. Combined therapy is expected to improve efficacy and patient outcomes significantly.

Broadening horizons: the role of ferroptosis in polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a common heterogeneous reproductive endocrine metabolic disorder in women of reproductive age characterized by clinical and biochemical hyperandrogenemia, ovulation disorders, and polycystic ovarian morphology. Ferroptosis is a novel type of cell death driven by iron accumulation and lipid peroxidation. Ferroptosis plays a role in maintaining redox balance, iron metabolism, lipid metabolism, amino acid metabolism, mitochondrial activity, and many other signaling pathways linked to diseases. Iron overload is closely related to insulin resistance, decreased glucose tolerance, and the occurrence of diabetes mellitus. There is limited research on the role of ferroptosis in PCOS. Patients with PCOS have elevated levels of ferritin and increased reactive oxygen species in ovarian GCs. Studying ferroptosis in PCOS patients is highly important for achieving personalized treatment. This article reviews the progress of research on ferroptosis in PCOS, introduces the potential connections between iron metabolism abnormalities and oxidative stress-mediated PCOS, and provides a theoretical basis for diagnosing and treating PCOS.

Analytical method development for α-amanitin and ß-amanitin in plasma at ultra-trace level by online solid phase extraction-high performance liquid chromatography-triple quadrupole mass spectrometry and its application in poisoning events.

α-Amanitin and ß-amanitin are the main fatal mushroom toxins. The toxins metabolize rapidly in blood and are reported hard to be detected 24 h after poisoning. The main challenge is that of developing a highly sensitive method at sub-pg mL-1 level in blood to diagnose intoxication cause and to study the poisoning mechanism and blood toxicity kinetics. An analytical method for α-amanitin and ß-amanitin at ultra-trace level was developed in this study by online solid phase extraction-high performance liquid chromatography-triple quadrupole mass spectrometry (online SPE-LC-MS/MS). Simple protein precipitation and liquid-liquid extraction were introduced to resolve the sample preparation problem of the online SPE-LC-MS/MS system with large-volume injection. A quick valve-switching technique with a quantitative loop as interface was used in the online system. This design can ensure the independence of flow path and pressure between the SPE and LC-MS/MS modules and can obtain the precise cleanup of the toxins. The limits of detection for α-amanitin and ß-amanitin in plasma were both 0.02 ng mL-1. The linear ranges were 0.05-20 ng mL-1 with a correlation coefficient r >0.99. The average recoveries at three spiking levels were 82.9 %-92.2 % with the relative standard deviations (RSD) of 5.4 %-8.0 % for α-amanitin and 84.5 %-93.9 % with RSDs of 4.5 %-7.8 % for ß-amanitin. The composition and concentration of the toxins in plasma from 18 patients in 5 mushroom poisoning events caused by aminitins were studied. The developed method has high positive confirmation ability and can identify toxins in plasma 40 h after poisoning.

Determination of ibotenic acid and muscimol in plasma by liquid chromatography-triple quadrupole mass spectrometry with bimolecular dansylation.

Ibotenic acid (IBA) is an amino acid and muscimol (MUS) is the decarboxyl derivative of IBA. They are mushroom neurotoxins with high polarity and low molecular weight. Only one transition (159->113 for IBA and 115->98 for MUS) can be found when directly measured by high performance liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS). Therefore, the identification and quantification of trace amount of the toxins in biomaterial are difficult. A highly sensitive and accurate analytical method for IBA and MUS in plasma was developed by LC-MS/MS with the application of bimolecular dansylation and internal standard calibration. Acetonitrile was used for protein precipitation and for toxin extraction from plasma. The toxins and internal standards (L-tyrosine-13C9,15N for IBA and tyramine-d4 for MUS) were derivatized with dansyl chloride (DNSCl). The reaction conditions of the bimolecular dansylation were optimized and the fragmentation pathways of the derivatives in MS/MS were studied. Method validation was carried out according to the Bioanalytical Method Validation Guidance for Industry (FDA, USA, 2018). The limits of detection for IBA and MUS in plasma were 0.3 ng mL-1 and 0.1 ng mL-1, respectively. The linear ranges in plasma were 1-500 ng mL-1 and 1-200 ng mL-1 with the correlation coefficients of 0.998 and 0.999 for IBA and MUS, respectively. The recoveries at three spiked levels were 90.7-111.4% with relative standard deviations (RSDs) of 6.4-10.3% for IBA and the results were 85.1-94.2% with RSDs of 5.0-8.9% for MUS. The toxin levels in patients' plasma samples under different poisoning degree were presented.

Bis(imino)aryl NCN pincer cobalt complexes: synthesis and disproportionation.

Treatment of iPr[NCN]Br (2,6-(2,6-iPr2C6H3C[double bond, length as m-dash]N)2C6H3Br) with nBuLi in THF and the subsequent addition of 1 equiv. of CoCl2, CoCl2(Ph3P)2, and CoBr2 gave pincer Co(ii) complexes {iPr[NCN]Co(µ-Cl)}2 (1d), iPr[NCN]CoClPh3P (1d-Ph3P), and iPr[NCN]CoBr2·Li(THF)4 (1d-LiBr) respectively in moderate yields, whereas the slow addition of in situ prepared iPr[NCN]Li to CoCl2 in THF afforded an unexpected mixed-valence cobalt(i/ii) complex κ2C,N,η6-iPr[NCN]Co-κN-CoCl3·Li(THF)4 (2d). Complex 2d was probably formed via a disproportionation reaction of the iPr[NCN]Co(ii) species with excess CoCl2 during the reaction. Nevertheless, addition of CoCl2 to in situ formed 1d-THF at room temperature did not lead to 2d but gave a trinuclear Co(ii) complex {iPr[NCN]Co(µ-Cl)(µ-Br/Cl)}2Co (1d-CoCl2) in moderate yield. Similar reactions using ligands containing small ortho groups in the imine moieties R[NCN]Br (2,6-(2,6-Me2C6H3C[double bond, length as m-dash]N)2C6H3Br, Me[NCN]Br; 2,6-(2,6-Et2C6H3C[double bond, length as m-dash]N)2C6H3Br, Et[NCN]Br; 2,6-(2,4,6-Me3C6H2C[double bond, length as m-dash]N)2C6H3Br, Mes[NCN]Br) and CoBr2, regardless of the reactant addition sequence, afforded mixed-valence cobalt(i/ii) complexes {κ2C,N,η6-R[NCN]Co-κN-CoBr(µ-Br)}2 (Me[NCN] (2a), Et[NCN] (2b), and Mes[NCN] (2c)), suggesting that the bulkiness of the ortho-groups in the imine moieties of the ligands plays an important role in the disproportionation reaction. In the presence of PMe3, Co(ii) complexes κ2C,N-R[NCN]CoBr(PMe3)2 (3a-d) and a bisligated cobalt(ii) complex κ3N,C,N-κ2C,N-iPr[NCN]2CoPMe3 (4d) can be prepared respectively in high yields. The molecular structures of 1d-LiBr, 1d-CoCl2, 2b, 2d, 3a, and 4d were confirmed by X-ray crystallographic analysis and the detailed mechanisms of the disproportionation reaction were proposed.

Expression profiles of mRNA and long noncoding RNA in the ovaries of letrozole-induced polycystic ovary syndrome rat model through deep sequencing.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. However, the exact pathophysiology of PCOS remains largely unclear. We performed deep sequencing to investigate the mRNA and long noncoding RNA (lncRNA) expression profiles in the ovarian tissues of letrozole-induced PCOS rat model and control rats. A total of 2147 mRNAs and 158 lncRNAs were differentially expressed between the PCOS models and control. Gene ontology analysis indicated that differentially expressed mRNAs were associated with biological adhesion, reproduction, and metabolic process. Pathway analysis results indicated that these aberrantly expressed mRNAs were related to several specific signaling pathways, including insulin resistance, steroid hormone biosynthesis, PPAR signaling pathway, cell adhesion molecules, autoimmune thyroid disease, and AMPK signaling pathway. The relative expression levels of mRNAs and lncRNAs were validated through qRT-PCR. LncRNA-miRNA-mRNA network was constructed to explore ceRNAs involved in the PCOS model and were also verified by qRTPCR experiment. These findings may provide insight into the pathogenesis of PCOS and clues to find key diagnostic and therapeutic roles of lncRNA in PCOS.

Optimization for quick, easy, cheap, effective, rugged and safe extraction of mycotoxins and veterinary drugs by response surface methodology for application to egg and milk.

A multiclass method was proposed for the simultaneous determination of various classes of veterinary drugs (n = 65), mycotoxins and metabolites (n = 39) in egg and milk by ultra-high performance liquid chromatography-tandem mass spectrometry. The contaminants were extracted by QuEChERS-based strategy including salt-out partitioning and dispersive solid-phase extraction for cleanup further. With the aim of maximizing throughput and extraction efficiency, Plackett-Burman design was employed initially for screening significant variables. And response surface methodology based on central composite design was conducted to achieve optimal conditions in details: 3.35% (v/v) of formic acid in acetonitrile, 1.2 g of NaCl, 0.5 g of anhydrous NaAc, 300 mg of C18 and 140 mg of primary secondary amine. Satisfactory analytical characteristics in validation, in aspects of accuracy (70%-105% for mycotoxins and quinolones, 55%-80% for sulphonamides and 40%-105% for other veterinary drugs), precision (inter-day RSDs < 14%) and sensitivity (LOQs ranged from 0.01 µg/kg to 31 µg/kg), were achieved under the optimized conditions. The matrix effects were evaluated and compensated by the use of matrix-matched calibration curves (R2 > 0.987). In practice, 45 eggs and 30 milk samples were investigated by the established method, of which positive finding aflatoxin in milk and sterigmatocystin in eggs.

Analysis of monofluoroacetic acid in urine by liquid chromatography-triple quadrupole mass spectrometry and preparation of the positive sample by the bioconversion from monofluoroacetamide to monofluoroacetic acid in vitro.

Whether as a rodenticide or as a natural product, monofluoroacetic acid (FAcOH) may cause poisoning to humans or animals for its high acute toxicity. Urine is one of the most typical specimens for forensic diagnosis when poisoning case about FAcOH happens. The positive sample containing FAcOH plays a key role for the development of an accurate and reliable analytical method. The bioconversion from monofluoroacetamide (FAcNH2) to FAcOH in urine in vitro was studied for the preparation of positive urine sample containing FAcOH without standard spiking or animal experiment. The average bioconversion rates were 0%, 18.6% and 41.3% when incubated the FAcNH2 spiked urine in vitro for 21days at -20°C, room temperature (RT) and 37°C, respectively. Afterwards, a fast and sensitive analytical method was developed for determination of FAcOH in urine. Samples were diluted with water containing formic acid and cleaned with polymeric anion exchange (PAX) cartridge. The acid eluate was neutralized with ammonium hydroxide and directly measured by hydrophilic interaction liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) using basic mobile phase condition. The limit of detection and limit of quantification of FAcOH in urine were 2 and 5ngmL(-1), respectively. The linear range was 5-1000ngmL(-1) with a correlation coefficient of r=0.9993 in urine calibrated with internal standard. The recoveries at four spiking levels (5, 10, 50 and 500ngmL(-1) in urine) were 87.2%-107% with relative standard deviations ranged between 4.3%-8.8%.