SLC7A11 promotes EMT and metastasis in invasive pituitary neuroendocrine tumors by activating the PI3K/AKT signaling pathway.

Invasive pituitary neuroendocrine tumors (PitNETs) are the most prevalent types of intracranial and neuroendocrine tumors. Their aggressive growth and difficulty in complete resection result in a high recurrence rate. Cystine transporter solute carrier family 7 member 11 (SLC7A11) is overexpressed in various cancers, which contributes to tumor growth, progression, and metastasis by promoting cystine uptake and glutathione biosynthesis. We identified SLC7A11 as an invasive biomarker based on three Gene Expression Omnibus cohorts. This study aimed to investigate the role of SLC7A11 in invasive PitNETs. Cell proliferation was assessed using CCK-8 and colony formation assays, while cell apoptosis was estimated with flow cytometry. Wound healing assays and transwell assays were utilized to evaluate migration and invasion ability. Our findings demonstrated that SLC7A11 was markedly upregulated in invasive PitNETs, and was associated with the invasiveness of PitNETs. Knockdown of SLC7A11 could largely suppress tumor cell proliferation, migration, and invasion, while inducing apoptosis. Furthermore, SLC7A11 depletion was implicated in regulating epithelial-mesenchymal transition and inactivating the PI3K/AKT signaling pathway. These insights suggest SLC7A11 as a potential therapeutic target for invasive PitNETs.

Evaluation of molecular residual disease in operable non-small cell lung cancer with gene fusions, MET exon skipping or de novo MET amplification.

Gene fusions and MET alterations are rare and difficult to detect in plasma samples. The clinical detection efficacy of molecular residual disease (MRD) based on circulating tumor DNA (ctDNA) in patients with non-small cell lung cancer (NSCLC) with these mutations remains unknown. This prospective, non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions (ALK, ROS1, RET, and FGFR1), MET exon 14 skipping or de novo MET amplification. We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021- and 338-gene panels, respectively. Detectable MRD correlated with a significantly higher recurrence rate (P < 0.001), yielding positive predictive values of 100% and 90.9%, and negative predictive values of 82.4% and 86.4% at landmark and longitudinal time points, respectively. Patients with detectable MRD showed reduced disease-free survival (DFS) compared to those with undetectable MRD (P < 0.001). Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not (P = 0.05). To our knowledge, this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET alterations. Patients with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.

Electronegative Phosphorus-Integrated Co2+ Active Sites for Enhanced Electrocatalytic Nitrogen Reduction.

In the quest for proficient electrocatalysts for ammonia's electrocatalytic nitrogen reduction, cobalt oxides, endowed with a rich d-electron reservoir, have emerged as frontrunners. Despite the previously evidenced prowess of CoO in this realm, its ammonia yield witnesses a pronounced decline as the reaction unfolds, a phenomenon linked to the electron attrition from its Co2+ active sites during electrocatalytic nitrogen reduction reaction (ENRR). To counteract this vulnerability, we harnessed electron-laden phosphorus (P) elements as dopants, aiming to recalibrate the electronic equilibrium of the pivotal Co active site, thereby bolstering both its catalytic performance and stability. Our empirical endeavors showcased the doped P-CoO's superior credentials: it delivered an impressive ammonia yield of 49.6 and, notably, a Faradaic efficiency (FE) of 9.6% at -0.2 V versus RHE, markedly eclipsing its undoped counterpart. Probing deeper, a suite of ex-situ techniques, complemented by rigorous theoretical evaluations, was deployed. This dual-pronged analysis unequivocally revealed CoO's propensity for an electron-driven valence metamorphosis to Co3+ post-ENRR. In stark contrast, P-CoO, fortified by P doping, exhibits a discernibly augmented ammonia yield. Crucially, P's intrinsic ability to staunch electron leakage from the active locus during ENRR ensures the preservation of the valence state, culminating in enhanced catalytic dynamism and fortitude. This investigation not only illuminates the intricacies of active site electronic modulation in ENRR but also charts a navigational beacon for further enhancements in this domain.

Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer.

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

(+)-Catechin ameliorates diabetic nephropathy injury by inhibiting endoplasmic reticulum stress-related NLRP3-mediated inflammation.

Endoplasmic reticulum (ER) stress and chronic sterile inflammation are associated with the pathogenesis of diabetic nephropathy (DN). Catechins are natural polyphenolic compounds found in green tea that possess some health benefits. However, whether (+)-catechin can reduce tubular injury in DN by regulating ER stress and NLRP3-associated inflammation remains uncertain. This study examined the effects of (+)-catechin on streptozotocin (STZ)-induced diabetic mice and on palmitic acid (PA)-treated HK-2 cells. In vivo, a DN mouse model was generated by injecting STZ. The biochemical indicators of serum and urine, as well as renal histopathology and ultrastructure were analysed. To predict the mechanisms associated with (+)-catechin, network pharmacology and molecular docking were used. Finally, quantitative real-time PCR (qPCR), western blot analysis and immunofluorescence analysis were performed to measure the mRNA and protein expressions of specific targets in the renal tissue of DN mice and PA-treated HK-2 cells to validate the predicted results. (+)-Catechin significantly ameliorated renal function and pathological changes associated with tubular injury by inhibiting ER stress by downregulating of GRP78, PEAK, CHOP, ATF6 and XBP1. In addition, (+)-catechin inhibited renal inflammation by suppressing NLRP3 associated inflammation, which was characterized by the downregulation of NLRP3, ASC, AIM2, Caspase1, IL-1ß and IL-18 in DN mice and PA-treated HK-2 cells. Collectively, these findings suggested that (+)-catechin exerted a renoprotective effect against DN by inhibiting ER stress and NLRP3-related inflammation to ameliorate tubular injury, suggesting the therapeutic potential of (+)-catechin.

Postoperative ctDNA in indicating the recurrence risk and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a potential novel biomarker to predict molecular residual disease (MRD) in lung cancer after definitive treatment. Herein, we investigated the value of ctDNA in prognosing risk of relapse and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer (NSCLC). METHODS: We enrolled 58 NSCLC patients in a real-world setting, and 58 tumor tissues and 325 plasma samples were analyzed. Tumor tissues and plasma samples were subjected to targeted next-generation sequencing (NGS) of 1021 cancer-related and ultra-deep targeted NGS covering 338 genes, respectively. RESULTS: ctDNA was detected in 31.0% of cases at the first postoperative time, which was associated with advanced tumor stage, T stage and KEAP1 or GRIN2A mutations in tissues. ctDNA positivity at landmark and longitudinal indicated the shorter disease-free survival. For patients with ctDNA positivity at the first postoperative time, regardless of adjuvant therapy, all patients who were persistently ctDNA positive during postoperative surveillance had disease recurrence. Among the patients who were ctDNA negative, only two patients (15.4%, 2/13) receiving adjuvant therapy relapsed, while one patient (50.0%, 1/2) without adjuvant therapy relapsed. For the first postoperative ctDNA negative patients, the recurrence rate of patients with adjuvant therapy was and higher than without adjuvant therapy (22.6% [7/31] vs. 11.1% [1/9]). The patients who became ctDNA positive may also benefit from intervention therapy. CONCLUSION: Postoperative ctDNA is a prognostic marker, and ctDNA-detection may facilitate personalized adjuvant therapy, and applying adjuvant therapy to the patients with detectable ctDNA could bring clinical benefits for them.

Emodin alleviates CRS4-induced mitochondrial damage via activation of the PGC1α signaling.

Cardiorenal syndrome type 4 (CRS4), a progressive deterioration of cardiac function secondary to chronic kidney disease (CKD), is a leading cause of death in patients with CKD. In this study, we aimed to investigate the cardioprotective effect of emodin on CRS4. C57BL/6 mice with 5/6 nephrectomy and HL-1 cells stimulated with 5% CKD mouse serum were used for in vivo and in vitro experiments. To assess the cardioprotective potential of emodin, we employed a comprehensive array of methodologies, including echocardiography, tissue staining, immunofluorescence staining, biochemical detection, flow cytometry, real-time quantitative PCR, and western blot analysis. Our results showed that emodin exerted protective effects on the function and structure of the residual kidney. Emodin also reduced pathologic changes in the cardiac morphology and function of these mice. These effects may have been related to emodin-mediated suppression of reactive oxygen species production, reduction of mitochondrial oxidative damage, and increase of oxidative metabolism via restoration of PGC1α expression and that of its target genes. In contrast, inhibition of PGC1α expression significantly reversed emodin-mediated cardioprotection in vivo. In conclusion, emodin protects the heart from 5/6 nephrectomy-induced mitochondrial damage via activation of the PGC1α signaling. The findings obtained in our study can be used to develop effective therapeutic strategies for patients with CRS4.

Circulating tumor DNA analysis predicts recurrence and avoids unnecessary adjuvant chemotherapy in I-IV colorectal cancer.

Background: Circulating tumor DNA (ctDNA) has emerged as a biomarker that can define the risk of recurrence after curative-intent surgery for patients with colorectal cancer (CRC). However, beyond the predictive power of postoperative ctDNA detection, the efficacy and potential limitations of ctDNA detection urgently need to be fully elucidated in a large cohort of CRC. Objectives: To define potentially cured CRC patients through ctDNA monitoring following surgery. Design: A prospective, multicenter, observational study. Methods: We enrolled 309 patients with stages I-IV CRC who underwent definitive surgery. Tumor tissues were sequenced by a custom-designed next-generation sequencing panel to identify somatic mutations. Plasma was analyzed using a ctDNA-based molecular residual disease (MRD) assay which integrated tumor-genotype-informed and tumor-genotype-naïve ctDNA analysis. The turnaround time of the assay was 10-14 days. Results: Postoperative ctDNA was detected in 5.4%, 13.8%, 15%, and 30% of patients with stage I, II, III, and IV disease, respectively, and in 17.5% of all longitudinal samples. Patients with positive postsurgery MRD had a higher recurrence rate than those with negative postsurgery MRD [hazard ratio (HR), 13.17; p < 0.0001], producing a sensitivity of 64.6%, a specificity of 94.8%, a positive predictive value (PPV) of 75.6%, and a negative predictive value (NPV) of 91.5%. Furthermore, patients with positive longitudinal MRD also had a significantly higher recurrence rate (HR, 14.44; p < 0.0001), with increased sensitivity (75.0%), specificity (94.9%), PPV (79.6%), and NPV (93.4%). Subgroup analyses revealed that adjuvant therapy did not confer superior survival for patients with undetectable or detectable MRD. In addition, MRD detection was less effective in identifying lung-only and peritoneal metastases. Conclusion: Postoperative ctDNA status is a strong predictor of recurrence independent of stage and microsatellite instability status. Longitudinal undetectable MRD could be used to define the potentially cured population in CRC patients undergoing curative-intent surgery.

Adjuvant Therapy-Free Strategy for Stage IB to IIIA Non-Small-Cell Lung Cancer Patients After Radical Resection Based on Longitudinal Undetectable Molecular Residual Disease: Prospective, Multicenter, Single-Arm Study (CTONG 2201).

BACKGROUND: The utility of circulating tumor DNA to monitor molecular residual disease (MRD) has been clinically confirmed to predict disease recurrence in non-small cell lung cancer (NSCLC) patients after radical resection. Patients with longitudinal undetectable MRD show a favorable prognosis and might not benefit from adjuvant therapy. PATIENTS AND METHODS: The CTONG 2201 trial is a prospective, multicenter, single-arm study (ClinicalTrials.gov identifier, NCT05457049), designed to evaluate the hypothesis that no adjuvant therapy is needed for patients with longitudinal undetectable MRD. Pathologically confirmed stage IB-IIIA NSCLC patients who have undergone radical resection will be screened. Only patients with 2 consecutive rounds of undetectable MRD will be enrolled (first at days 3-10, second at days 30 ± 7 after surgery), and admitted for imaging and MRD monitoring every 3 months without adjuvant therapy. The primary endpoint is the 2-year disease-free survival rate for those with longitudinal undetectable MRD. The recruitment phase began in August 2022 and 180 patients will be enrolled. CONCLUSIONS: This prospective trial will contribute data to confirm the negative predictive value of MRD on adjuvant therapy for NSCLC patients. CLINICAL TRIAL REGISTRATION: NCT05457049 (CTONG 2201).

Transcriptomic and metabolomic analyses reveals keys genes and metabolic pathways in tea (Camellia sinensis) against six-spotted spider mite (Eotetranychus Sexmaculatus).

BACKGROUND: Six-spotted spider mite (Eotetranychus sexmaculatus) is one of the most damaging pests of tea (Camellia sinensis). E. sexmaculatus causes great economic loss and affects tea quality adversely. In response to pests, such as spider mites, tea plants have evolved resistance mechanisms, such as expression of defense-related genes and defense-related metabolites. RESULTS: To evaluate the biochemical and molecular mechanisms of resistance in C. sinensis against spider mites, "Tianfu-5" (resistant to E. sexmaculatus) and "Fuding Dabai" (susceptible to E. sexmaculatus) were inoculated with spider mites. Transcriptomics and metabolomics based on RNA-Seq and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) technology were used to analyze changes in gene expression and metabolite content, respectively. RNA-Seq data analysis revealed that 246 to 3,986 differentially expressed genes (DEGs) were identified in multiple compared groups, and these DEGs were significantly enriched in various pathways, such as phenylpropanoid and flavonoid biosynthesis, plant-pathogen interactions, MAPK signaling, and plant hormone signaling. Additionally, the metabolome data detected 2,220 metabolites, with 194 to 260 differentially abundant metabolites (DAMs) identified in multiple compared groups, including phenylalanine, lignin, salicylic acid, and jasmonic acid. The combined analysis of RNA-Seq and metabolomic data indicated that phenylpropanoid and flavonoid biosynthesis, MAPK signaling, and Ca2+-mediated PR-1 signaling pathways may contribute to spider mite resistance. CONCLUSIONS: Our findings provide insights for identifying insect-induced genes and metabolites and form a basis for studies on mechanisms of host defense against spider mites in C. sinensis. The candidate genes and metabolites identified will be a valuable resource for tea breeding in response to biotic stress.

Built-in Electric Field-Induced Work Function Reduction in C-Co3O4 for Efficient Electrochemical Nitrogen Reduction.

Co3O4 is a highly selective catalyst for the electrochemical conversion of N2 to NH3. However, the large work function (WF) of Co3O4 leads to unsatisfactory activity. To address this issue, a strong built-in electric field (BIEF) was constructed in Co3O4 by doping C atoms (C-Co3O4) to reduce the WF for improving the electrocatalytic performance. C-Co3O4 exhibited a remarkable NH3 yield of 38.5 µg h-1 mgcat-1 and a promoted FE of 15.1% at -0.3 V vs RHE, which were 2.2 and 1.9 times higher than those of pure Co3O4, respectively. Kelvin probe force microscopy (KPFM), zeta potential, and ultraviolet photoelectron spectrometry (UPS) confirmed the formation of strong BIEF and WF reduction in C-Co3O4. Additionally, in situ Raman measurements and density functional theory (DFT) calculations revealed the relationship between BIEF and WF and provided insights into the reaction mechanism. Our work offers valuable guidance for the design and development of more efficient nitrogen reduction catalysts.

Mutational profiling of Chinese patients with thyroid cancer.

Background: The incidence of thyroid cancer in China has rapidly increased in recent decades. As the genetic profiles of thyroid cancer vary dramatically between different geographical regions, a comprehensive genetic landscape of thyroid cancer in the Chinese population is urgently needed. Methods: We retrospectively included thyroid cancer patients from three Chinese medical centers between February 2015 and August 2020. To dissect the genomic profiling of these patients, we performed targeted next-generation sequencing on their tumor tissues using a 1,021-gene panel. Results: A total of 458 Chinese patients with thyroid cancer were enrolled, including four malignant histological subtypes arising from follicular epithelial thyroid cells. BRAF driver mutations were identified in 76.0% of patients, followed by RET rearrangements (7.6%) and RAS driver mutations (4.1%). Tumors with more somatic mutations correlated with worse clinical characteristics, including older age at diagnosis, less differentiation of tumor, larger tumor size, lymph node metastasis and distal metastasis. Subclonal BRAF mutations occurred in 20% (6/30) of patients and were frequent in poorly differentiated or anaplastic tumors (33.3% [2/6] vs. 4.2% [1/24], P = 0.09) and those with distal metastasis (50.0% [2/4] vs. 8.7% [2/23], P = 0.09). Tumors with TERT promoter mutations had significantly more somatic mutations (average: 6.5 vs. 1.8, P < 0.001). Moreover, TERT promoter mutations were not associated with lymph node metastasis but significantly associated with older age at diagnosis and poorly differentiated or anaplastic tumors, regardless of their clonal architecture. Conclusion: Our results shed light on the molecular pathogenesis and clinical characteristics of thyroid cancer in the Chinese population. The number of somatic mutations, TERT promoter mutations, and the clonal architecture of BRAF mutations should be considered in the risk stratification of thyroid cancer.

miR-491-5p regulates the susceptibility of glioblastoma to ferroptosis through TP53.

BACKGROUND: Ferroptosis has excellent potential in glioblastoma (GBM) therapy. In this study, we attempted to explore the effect of miR 491-5p on ferroptosis in GBM. METHODS: In this study, publicly available ferroptosis-related genome maps were used to screen genes upregulated in GBM and their target genes. The Spearman correlation coefficient was applied to analyze the correlation between the tumor protein p53 gene (TP53) and miR-491-5p. The expressions of miR-491-5p and TP53 were determined. The protein abundances of the TP53-encoded factors p53 and p21 were measured. Cell proliferation, migration and invasion were assessed. We pretreated U251MG cells and GBM mice with a ferroptosis inducer (erastin). The mitochondrial state was observed. The contents of reactive oxygen species (ROS), total Fe and Fe2+ were calculated. RESULTS: The level of TP53 was significantly increased in GBM and negatively correlated with miR-491-5p. miR-491-5p overexpression promoted U251MG cell proliferation, migration and invasion and interfered with the p53/p21 pathway. TP53 supplement reversed the effects of miR-491-5p. U251MG cells and GBM mice exhibited significant accumulations of ROS and iron. Erastin promoted the expression of TP53. Inhibition of TP53 reversed erastin-induced physiological phenotypes. Moreover, miR-491-5p overexpression caused a decrease in the number of damaged mitochondria and the contents of ROS, total Fe and Fe2+. TP53 supplement disrupted miR-491-5p-repressed ferroptosis. Erastin could inhibit GBM growth, and miR-491-5p overexpression impeded the therapeutic effect of erastin. CONCLUSIONS: Our findings reveal the functional diversity of miR-491-5p in GBM and suggest that miR-491-5p/TP53 signaling hinders the sensitivity of GBM to ferroptosis through the p53/p21 pathway.

Genomic landscape and efficacy of HER2-targeted therapy in patients with HER2-mutant non-small cell lung cancer.

Background: HER2-targeted therapy provides survival benefits to HER2-mutant non-small cell lung cancer (NSCLC). A better understanding of the clinical and genomic characterization of treatment-naïve HER2-positive NSCLC, as well as the efficacy of and resistance to HER2-targeted therapy in HER2-altered NSCLC, could promote further improvement of HER2 targeted therapy. Methods: HER2-altered NSCLC patients was retrospectively included and their genomic profiles were performed by next-generation sequencing. The clinical outcomes included overall response rate, disease control rate and progression-free survival. Results: Among 176 treatment-naïve patients with HER2 alterations, 64.8% harbored HER2 mutations with/without HER2 amplification, and 35.2% carried HER2 amplification only. Molecular characterization was correlated with tumor stage that late-stage NSCLC with HER2 oncogenic mutations showed a higher prevalence of TP53 mutations and a higher tumor mutation burden. However, this correlation was not found in patients with HER2 amplification only. Twenty-one patients with HER2 alterations treated with pyrotinib or afatinib were retrospectively enrolled. Pyrotinib yielded a longer median progression-free survival than afatinib (5.9 [95% CI, 3.8-13.0] vs. 4.0 months [95% CI, 1.9-6.3], P = 0.06) in these patients. Analysis of the genomic profiles before and after anti-HER2 targeted therapies identified de novo HER2 copy number gain and G518W mutation, as well as mutations involving DNA damage repair signaling, SWI-SNF complex, and epigenetic regulations as potential resistance mechanisms. Conclusion: HER2-mutant NSCLC had different molecular features from HER2-amplified NSCLC, and its genomic profile was dependent of tumor stage. Pyrotinib had superior therapeutic effects than afatinib in HER2-altered NSCLC, although larger cohorts are warranted to validate it. HER2-dependent and -independent resistance mechanisms to afatinib and pyrotinib were unveiled.

Regulation of the Work Function Difference Promotes In Situ Phase Transition of WO3-x for Efficient Formate Electrooxidation.

Direct formate fuel cells (DFFCs) have drawn tremendous attention because they are environmentally benign and have good safety. However, the lack of advanced catalysts for formate electrooxidation hinders the development and applications of DFFCs. Herein, we report a strategy of regulating the metal-substrate work function difference to effectively promote the transfer of adsorbed hydrogen (Had), thus enhancing formate electrooxidation in alkaline solutions. By introducing rich oxygen vacancies, the obtained catalysts of Pd/WO3-x-R show outstanding formate electrooxidation activity, exhibiting an extremely high peak current of 15.50 mA cm-2 with a lower peak potential of 0.63 V. In situ electrochemical Fourier transform infrared and in situ Raman measurements verify an enhanced in situ phase transition from WO3-x to HxWO3-x during the formate oxidation reaction process over the Pd/WO3-x-R catalyst. The results of experimental and density functional theory (DFT) calculations confirm that the work function difference (ΔΦ) between the metal (Pd) and substrate (WO3-x) would be regulated by inducing oxygen vacancies in the substrate, resulting in improved hydrogen spillover at the interface of the catalyst, which is essentially responsible for the observed high performance of formate oxidation. Our findings provide a novel strategy of rationally designing efficient formate electrooxidation catalysts.

Postoperative circulating tumor DNA can refine risk stratification in resectable lung cancer: results from a multicenter study.

Circulating tumor DNA (ctDNA) has potential as a promising biomarker for molecular residual disease (MRD) detection in lung cancer. As the next-generation sequencing standardized panel for ctDNA detection emerges, its clinical utility needs to be validated. We prospectively recruited 184 resectable lung cancer patients from four medical centers. Serial postoperative ctDNAs were analyzed by a standardized panel. A total of 427 postoperative plasma samples from 177 eligible patients were enrolled. ctDNA positivity after surgery was an independent predictor for disease recurrence and preceded radiological recurrence by a median of 6.6 months (range, 0.7-27.0 months). ctDNA-positive or -negative patients with tumors of any stage had similar disease-free survival (DFS). Patients who received targeted therapy had significantly improved DFS than those not receiving adjuvant therapy or receiving chemotherapy, regardless of baseline/preadjuvant ctDNA status. According to whether the ctDNA variants were detected in its matched tissue, they were classified into tissue derived and non-tissue derived. Patients with detectable postoperative ctDNA with tissue-derived mutations had comparable DFS with those with non-tissue-derived mutations. Collectively, we demonstrated that postoperative ctDNA has the potential to stratify prognosis and optimize tumor stage in resectable lung cancer. ctDNA variants not identified in tissue samples should be considered in MRD test.

Soyasaponin I alleviates hypertensive intracerebral hemorrhage by inhibiting the renin-angiotensin-aldosterone system.

BACKGROUND: Hypertensive intracerebral hemorrhage (HICH) is a life-threatening disease and lacks effective treatments. Previous studies have confirmed that metabolic profiles altered after ischemic stroke, but how brain metabolism changes after HICH was unclear. This study aimed to explore the metabolic profiles after HICH and the therapeutic effects of soyasaponin I on HICH. METHODS: HICH model was established first. Hematoxylin and eosin staining was used to estimate the pathological changes after HICH. Western blot and Evans blue extravasation assay were applied to determine the integrity of the blood-brain barrier (BBB). Enzyme-linked immunosorbent assay was used to detect the activation of the renin-angiotensin-aldosterone system (RAAS). Next, liquid chromatography-mass spectrometry-untargeted metabolomics was utilized to analyze the metabolic profiles of brain tissues after HICH. Finally, soyasaponin I was administered to HICH rats, and the severity of HICH and activation of the RAAS were further assessed. RESULTS: We successfully constructed HICH model. HICH significantly impaired BBB integrity and activated RAAS. HICH increased PE(14:0/24:1(15Z)), arachidonoyl serinol, PS(18:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, and 19Z)), PS(20:1(11Z)/20:5(5Z, 8Z, 11Z, 14Z, and 17Z)), glucose 1-phosphate, etc., in the brain, whereas decreased creatine, tripamide, D-N-(carboxyacetyl)alanine, N-acetylaspartate, N-acetylaspartylglutamic acid, and so on in the hemorrhagic hemisphere. Cerebral soyasaponin I was found to be downregulated after HICH and supplementation of soyasaponin I inactivated the RAAS and alleviated HICH. CONCLUSION: The metabolic profiles of the brains changed after HICH. Soyasaponin I alleviated HICH via inhibiting the RAAS and may serve as an effective drug for the treatment of HICH in the future.

Local Electric Field Induced by Atomic-Level Donor-Acceptor Couple of O Vacancies and Mn Atoms Enables Efficient Hybrid Capacitive Deionization.

Transition metal oxides suffer from slow salt removal rate (SRR) due to inferior ions diffusion ability in hybrid capacitive deionization (HCDI). Local electric field (LEF) can efficiently improve the ions diffusion kinetics in thin electrodes for electrochemical energy storage. Nevertheless, it is still a challenge to facilitate the ions diffusion in bulk electrodes with high loading mass for HCDI. Herein, this work delicately constructs a LEF via engineering atomic-level donor (O vacancies)-acceptor (Mn atoms) couples, which significantly facilitates the ions diffusion and then enables a high-performance HCDI. The LEF boosts an extended accelerated ions diffusion channel at the particle surface and interparticle space, resulting in both remarkably enhanced SRR and salt removal capacity. Convincingly, the theoretical calculations demonstrate that electron-enriched Mn atoms center coupled with an electron-depleted O vacancies center is formed due to the electron back-donation from O vacancies to adjacent Mn centers. The resulted LEF efficiently reduce the ions diffusion energy barrier. This work sheds light on the effect of atomic-level LEF on improving ions diffusion kinetics at high loading mass application and paves the way for the design of transition metal oxides toward high-performance HCDI applications.

Suprasellar Ganglioglioma Arising from the Third Ventricle Floor: A Case Report and Review of the Literature.

Gangliogliomas are uncommon intracranial tumors that include neoplastic and abnormal ganglion cells, and show positive immunohistochemical staining for GFAP and syn. This type of lesion occurs more frequently in the temporal lobe than in other areas; they are extremely rare in the suprasellar region. To the best of our knowledge, including our case, 19 cases of GGs have been found in the suprasellar region. Among them, five tumors invaded the optic nerve, nine tumors invaded the optic chiasm, one tumor invaded the optic tract, and two tumors invaded the entire optic chiasmal hypothalamic pathway. In the present study, we describe the first case of suprasellar GGs arising from the third ventricle floor that was removed through the endoscopic endonasal approach. In addition, we summarize the clinical characteristics of GGs, such as age of onset, gender distribution, MRI signs, main clinical symptoms, and treatment methods for GG cases.

Comprehensive analysis of T cell receptor repertoire in patients with KRAS mutant non-small cell lung cancer.

Background: Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes in non-small cell lung cancer (NSCLC). The administration of immunotherapy has demonstrated significant efficacy in prolonging the overall survival of patients with KRAS mutation in recent years. However, the efficacy of immunotherapy in KRAS mutant NSCLC is variable. Analysis of T cell receptor (TCR) repertoire may contribute to a better understanding of the mechanisms behind such differential outcomes. Methods: A total of 47 patients with KRAS mutant NSCLC were enrolled in this study. Deep sequencing of the TCR ß chain complementarity-determining regions in tumor tissue and paired peripheral blood specimens was conducted. Comprehensive analysis of TCR repertoire metrics was performed with different KRAS mutation subtypes and concomitant mutations. Moreover, the associations between TCR repertoire metrics and tumor mutation burden (TMB), as well as programmed death-ligand 1 were explored, respectively. Results: TCR repertoire metrics, including Shannon index, Clonality, and Morisita index (MOI), showed no significant differences among different KRAS mutation subtypes. The similar results were observed between patients with tumor protein p53 (TP53) mutation and those with wild-type TP53. In contrast, although no significant differences were found in Shannon index and Clonality, patients with KRAS/serine/threonine kinase 11 (STK11) comutation showed a significantly higher MOI compared to their STK11 wild-type counterparts (P=0.012). In addition, TCR repertoire metrics were neither associated with TMB nor programmed death-ligand 1 expression in KRAS mutant NSCLC. Conclusions: This retrospective study comprehensively described the TCR repertoire in KRAS mutant NSCLC. A higher MOI represented more overlap of the TCR repertoire between tumor tissue and paired peripheral blood, indicating distinctive immunological features in NSCLC with KRAS/STK11 comutation.