Association Between rs2278426 Polymorphism of the ANGPTL8 Gene and Polycystic Ovary Syndrome.

Purpose: To study the relationship between the single nucleotide polymorphism (SNP) rs2278426 in the angiopoietin-like protein 8 gene (ANGPTL8) and polycystic ovary syndrome (PCOS). Patients and methods: A total of 122 patients with PCOS and 108 controls were recruited for comparison of glucose, lipid, insulin, sex hormone, and ANGPTL8 levels. Polymerase chain reaction (PCR) and gene sequencing were performed for comparison of the frequency of the CC, CT, and TT rs2278426 genotypes and the rs2278426 allele distributions between the PCOS and control groups and between the obese and non-obese subgroups of the PCOS and control groups. Results: The frequency of the T allele was significantly higher in the PCOS group than that in the controls (P = 0.037). In the dominant genetic model, the proportion of the CT+TT genotype in the PCOS group was significantly higher than that in the controls (P = 0.047). Subgroup analysis demonstrated that the T allele proportion was significantly higher in obese PCOS group than obese control group (P = 0.027). PCOS with the CT+TT genotype had significantly higher body mass index (BMI; P = 0.001), triglyceride (TG; P = 0.005), homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.035), testosterone (P = 0.041), and ANGPTL8 (P = 0.037) levels and significantly lower high-density lipoprotein (HDL) levels (P = 0.025) than PCOS with the CC genotype. Obese PCOS group with the CT+TT genotype had significantly higher TG (P = 0.015), luteinizing hormone (LH; P = 0.030), fasting insulin (FINS; P = 0.039), HOMA-IR (P = 0.018), and ANGPTL8 (P = 0.049) levels than obese PCOS group with the CC genotype. Conclusion: Polymorphisms of rs2278426 may induce glycolipid metabolic disorders by affecting ANGPTL8 levels and functions in Han Chinese females with obesity from the Shandong region, increasing the risk of PCOS in this population.

Neural mechanisms of different types of envy: a meta-analysis of activation likelihood estimation methods for brain imaging.

Previous studies have a lack of meta-analytic studies comparing the trait (personality) envy, social comparison envy, and love-envy, and the understanding of the similarities and differences in the neural mechanisms behind them is relatively unclear. A meta-analysis of activation likelihood estimates was conducted using 13 functional magnetic resonance imaging studies. Studies first used single meta-analyses to identify brain activation areas for the three envy types. Further, joint and comparative analyses were followed to assess the common and unique neural activities among the three envy types. A single meta-analysis showed that the critical brain regions activated by trait (personality) envy included the inferior frontal gyrus, cingulate gyrus, middle frontal gyrus, lentiform nucleus and so on. The critical brain regions activated by social comparison envy included the middle frontal gyrus, inferior frontal gyrus, medial frontal gyrus, precuneus and so on. The critical brain regions activated by love-envy included the inferior frontal gyrus, superior frontal gyrus, cingulate gyrus, insula and so on. In terms of the mechanisms that generate the three types of envy, each of them is unique when it comes to the perception of stimuli in a context; in terms of the emotion regulation mechanisms of envy, the three types of envy share very similar neural mechanisms. Both their generation and regulation mechanisms are largely consistent with the cognitive control model of emotion regulation. The results of the joint analysis showed that the brain areas co-activated by trait (personality) envy and social comparison envy were frontal sub-Gyral, inferior parietal lobule, inferior frontal gyrus, precuneus and so on; the brain areas co-activated by trait (personality) envy and love-envy were extra-nuclear lobule, lentiform nucleus, paracentral lobule, cingulate gyrus and so on; the brain regions that are co-activated by social comparison envy and love-envy are anterior cingulate gyrus, insula, supramarginal gyrus, inferior frontal gyrus and so on. The results of the comparative analysis showed no activation clusters in the comparisons of the three types of envy.

EP300-ZNF384 transactivates IL3RA to promote the progression of B-cell acute lymphoblastic leukemia.

The EP300-ZNF384 fusion gene is an oncogenic driver in B-cell acute lymphoblastic leukemia (B-ALL). In the present study, we demonstrated that EP300-ZNF384 substantially induces the transcription of IL3RA and the expression of IL3Rα (CD123) on B-ALL cell membranes. Interleukin 3 (IL-3) supplementation promotes the proliferation of EP300-ZNF348-positive B-ALL cells by activating STAT5. Conditional knockdown of IL3RA in EP300-ZF384-positive cells inhibited the proliferation in vitro, and induced a significant increase in overall survival of mice, which is attributed to impaired propagation ability of leukemia cells. Mechanistically, the EP300-ZNF384 fusion protein transactivates the promoter activity of IL3RA by binding to an A-rich sequence localized at -222/-234 of IL3RA. Furthermore, forced EP300-ZNF384 expression induces the expression of IL3Rα on cell membranes and the secretion of IL-3 in CD19-positive B precursor cells derived from healthy individuals. Doxorubicin displayed a selective killing of EP300-ZNF384-positive B-ALL cells in vitro and in vivo. Collectively, we identify IL3RA as a direct downstream target of EP300-ZNF384, suggesting CD123 is a potent biomarker for EP300-ZNF384-driven B-ALL. Targeting CD123 may be a novel therapeutic approach to EP300-ZNF384-positive patients, alternative or, more likely, complementary to standard chemotherapy regimen in clinical setting.

Corrigendum: Mutation of Gemin5 causes defective hematopoietic stem/progenitor cells proliferation in zebrafish embryonic hematopoiesis.

[This corrects the article DOI: 10.3389/fcell.2021.670654.].

Tenascin C activates the toll­like receptor 4/NF­κB signaling pathway to promote the development of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a globally prevalent gynecological disorder among women of childbearing age. The present study aimed to investigate the role of tenascin C (TNC) in PCOS and its potential mechanisms. Fasting blood glucose and serum insulin, the homeostasis model assessment of insulin resistance and the serum hormone levels were determined in PCOS rats. In addition, H&E staining was used for assessing pathology. In addition, the effects of TNC on oxidative stress and inflammation response in PCOS rat and cell models was assessed. Furthermore, the roles of TNC on KGN cell proliferation and apoptosis were determined employing EdU assay and flow cytometry. TLR4/NF­κB pathway­related proteins were measured using western blotting, immunofluorescence and immunohistochemistry. It was found that the mRNA and protein expression was upregulated in PCOS rats and in KGN cells induced by dihydrotestosterone (DHT). Knockdown of TNC relieved the pathological characteristics and the endocrine abnormalities of PCOS rats. Knockdown of TNC inhibited ovarian cell apoptosis, oxidative stress and inflammation in PCOS rats. Knockdown of TNC reversed the DHT­induced reduction in cell proliferation and increase in apoptosis in KGN cells. Furthermore, knockdown of TNC alleviated oxidative stress and inflammatory responses induced by DHT in KGN cells. Additionally, knockdown of TNC inhibited the toll­like receptor 4 (TLR4)/NF­κB signaling pathway in PCOS rats and DHT­treated KGN cells. In conclusion, knockdown of TNC could ameliorate PCOS in both rats and a cell model by inhibiting cell apoptosis, oxidative stress and inflammation via the suppression of the TLR4/NF­κB signaling pathway.

Elongin B promotes breast cancer progression by ubiquitinating tumor suppressor p14/ARF.

Elongin B (ELOB), a pivotal element in the ELOB/c-Cullin2/5-SOCS-box E3 ubiquitin-protein ligase complex, plays a significant role in catalyzing the ubiquitination and subsequent degradation of a broad spectrum of target proteins. Notably, it is documented to facilitate these processes. However, the regulatory role of ELOB in breast cancer remains ambiguous. In this study, through bio-informatic analysis of The Cancer Genome Atlas and Fudan University Shanghai Cancer Center database, we demonstrated that ELOB was over-expressed in breast cancer tissues and was related to unfavorable prognosis. Additionally, pathway enrichment analysis illustrated that high expression of ELOB was associated with multiple cancer promoting pathways, like cell cycle, DNA replication, proteasome and PI3K - Akt signaling pathway, indicating ELOB as a potential anticancer target. Then, we confirmed that both in vivo and in vitro, the proliferation of breast cancer cells could be significantly suppressed by the down-regulation of ELOB. Mechanically, immunoprecipitation and in vivo ubiquitination assays prompted that, as the core element of Cullin2-RBX1-ELOB E3 ligase (CRL2) complex, ELOB regulated the ubiquitination and the subsequent degradation of oncoprotein p14/ARF. Moreover, the anticancer efficacy of erasing ELOB could be rescued by simultaneous knockdown of p14/ARF. Finally, through analyzing breast cancer tissue microarrays and western blot of patient samples, we demonstrated that the expression of ELOB in tumor tissues was elevated in compared to adjacent normal tissues. In conclusion, ELOB is identified to be a promising innovative target for the drug development of breast cancer by promoting the ubiquitination and degradation of oncoprotein p14/ARF.

Case Report: A rare case of intramedullary spinal cord abscess with brain abscess caused by Klebsiella pneumoniae underwent surgical intervention.

Background: Intramedullary Spinal Cord Abscess (ISCA) is an uncommon infectious disease of the central nervous system. Since its first report in 1830, there have been very few documented cases associated with it. Here, we present a case of ISCA with cerebral abscess caused by Klebsiella pneumoniae. Case presentation: A 55-year-old male patient presented with head and neck pain, fever, and left limb weakness for 5 days. The diagnosis of ISCA with brain abscess caused by Klebsiella pneumoniae was confirmed through sputum culture, cerebrospinal fluid gene test, pus culture, and magnetic resonance imaging (MRI) as well as computerized tomography (CT) scan. The patient had a history of pulmonary tuberculosis and old tuberculous foci were observed in the lung. Initially considering tuberculosis as the cause due to unclear etiology at that time, anti-tuberculosis treatment was administered. However, due to rapid deterioration in the patient's condition and severe neurological dysfunction within a short period of time after admission, surgical intervention including incision and drainage for intramedullary abscess along with removal of brain abscess was performed. Subsequent postoperative follow-up showed improvement in both symptoms and imaging findings. Conclusion: Early diagnosis of central nervous system (CNS) abscess coupled with prompt surgical intervention and administration of appropriate antibiotics are crucial factors in preventing disease progression and reducing mortality rates.

Global trends in burden of type 2 diabetes attributable to physical inactivity across 204 countries and territories, 1990-2019.

Background: To promote a comprehensive understanding of global trends and burden of type 2 diabetes attributable to physical inactivity. Methods: We utilized data regarding mortality, disability-adjusted life years (DALYs), as well as age-standardized mortality rates (ASMR) and DALYs rates (ASDR) derived from the global burden of disease study 2019 to evaluate the impact of physical inactivity on the prevalence of type 2 diabetes in 204 countries and territories over the period from 1990 to 2019. This method facilitated the analysis of the diabetes burden across different ages, genders, and regions. To determine the long-term progression of type 2 diabetes prevalence, we computed the estimated annual percentage change (EAPC) in burden rates. Results: Globally, the number of deaths and DALYs from type 2 diabetes due to physical inactivity more than doubled between 1990 and 2019. Concurrently, there was an increase in the ASMR and ASDR, with EAPC of 0.26 (95% CI: 0.13-0.39) and 0.84 (95% CI: 0.78-0.89), respectively. As of 2019, the global ASMR and ASDR for physical inactivity stood at 1.6 (95% UI: 0.8-2.7) per 100 000 and 55.9 (95% UI: 27.2-97.6) per 100 000, respectively. Notable disparities were observed in the type 2 diabetes burden associated with physical inactivity worldwide, with higher sociodemographic index (SDI) countries experiencing lower ASDR and ASMR compared to lower SDI countries. Initially, females exhibited higher ASMR and ASDR than males, but this gender disparity in ASMR and ASDR has lessened in recent years. The mortality and DALYs rates associated with physical inactivity exhibit an inverted V-shaped pattern across various age groups, predominantly affecting the elderly population. Conclusion: Between 1990 and 2019, there was a marked rise in the worldwide burden of type 2 diabetes associated with physical inactivity, underscoring the role of physical inactivity as a key changeable risk factor in the global landscape of this disease. This necessitates additional research to explore the variables contributing to the varying levels of disease burden across different countries and between sexes. Furthermore, it calls for the formulation of public health policies aimed at guiding prevention tactics, promoting early detection, and enhancing the management of type 2 diabetes.

Geniposide reduced oxidative stress-induced apoptosis in HK-2 cell through PI3K/AKT3/FOXO1 by m6A modification.

Exogenous hydrogen peroxide (H2O2) may generate excessive oxidative stress, inducing renal cell apoptosis related with kidney dysfunction. Geniposide (GP) belongs to the iridoid compound with anti-inflammatory, antioxidant and anti-apoptotic effects. This study aimed to observe the intervention effect of GP on H2O2-induced apoptosis in human kidney-2 (HK-2) cells and to explore its potential mechanism in relation to N6-methyladenosine (m6A) RNA methylation. Cell viability, apotosis rate and cell cycle were tested separately after different treatments. The mRNA and protein levels of m6A related enzymes and phosphoinositide 3-kinase (PI3K)/a serine/threonine-specific protein kinase 3 (AKT3)/forkhead boxo 1 (FOXO1) and superoxide dismutase 2 (SOD2) were detected by reverse transcription-quantitative real-time PCR (RT-qPCR) and Western blot. The whole m6A methyltransferase activity and the m6A content were measured by ELISA-like colorimetric methods. The changes of m6A methylation levels of PI3K/AKT3/FOXO1 and SOD2 were determined by methylated RNA immunoprecipitation (MeRIP)-qPCR. Multiple comparisons were performed by ANOVA with Turkey's post hoc test. Exposed to 400 µmol/L H2O2, cells were arrested in G1 phase and the apoptosis rate increased, which were significantly alleviated by GP. Compared with the H2O2 apoptosis group, both the whole m6A RNA methyltransferase activity and the m6A contents were increased due to GP intervention. Besides, the SOD2 protein was increased, while PI3K and FOXO1 decreased. The m6A methylation level of AKT3 was negatively correlated with its protein level. Taken together, GP affects the global m6A methylation microenvironment and regulates the expression of PI3K/AKT3/FOXO1 signaling pathway via m6A modification, alleviating cell cycle arrest and apoptosis caused by oxidative stress in HK-2 cells with a good application prospect.

Clinical significance of the combined test of seven blood coagulation indexes, lipids and platelet agglutination on hypercoagulable state of blood in parturient women.

Objective: To investigate the value of the combined test of seven blood coagulation indexes, lipids and platelet agglutination on the evaluation of the hypercoagulable state of blood in parturient women. Methods: This is a retrospective study. Total 50 high risk parturient women who underwent an antenatal examination in Baoding Maternal and Child Health Hospital from June 2021 to January 2023 were selected as the observation group, while 50 normal parturient women who underwent antenatal examination without comorbidities and complications were randomly collected in a ratio of 1:1 as the control group. All subjects had venous blood drawn for testing of seven blood coagulation indexes, lipids and platelet agglutination before delivery, and their general data were recorded. Results: The activated partial thromboplastin time(APTT) in the observation group was lower than that in the control group, while thrombin time(TT) and D-dimer(DD) were both higher than those in the control group, with statistically significant differences(p<0.05); total cholesterol (TC) and triglyceride (TG) in the observation group were both higher than those in the control group, with statistically significant differences (p<0.05); adenosine diphosphate (ADP) and arachidonic acid (AA) in the observation group were both higher than those in the control group, with statistically significant differences (p<0.05). Moreover, the overall incidence of adverse pregnancy was higher in the observation group than in the control group, with a statistically significant difference (p<0.05). Conclusions: The combined test of seven blood coagulation indexes, lipids and platelet agglutination results in excellent performance in predicting and judging the presence or absence of the hypercoagulable state of blood in parturient women, with the combination of APTT+TT+DD+TG+ADP+AA being the preferred test.

Anti-psoriasis effect of 18ß-glycyrrhetinic acid by breaking CCL20/CCR6 axis through its vital active group targeting GUSB/ATF2 signaling.

BACKGROUND: Psoriasis is an immune-mediated chronic inflammatory skin disease. Current research suggests that the long-term persistence and recurrence of psoriasis are closely related to the feedback loop formed between keratinocytes and immune cells, especially in Th 17 or DC cells expressing CCR6. CCL20 is the ligand of CCR6. Therefore, drugs that block the expression of CCL20 or CCR6 may have a certain therapeutic effect on psoriasis. Glycyrrhetinic acid (GA) is the main active ingredient of the plant drug licorice and is often used to treat autoimmune diseases, including psoriasis. However, its mechanism of action is still unclear. METHODS: Psoriasis like skin lesion model was established by continuously applying imiquimod on the back skin of normal mice and CCR6-/- mice for 7 days. The therapeutic and preventive effects of glycyrrhetinic acid (GA) on the model were observed and compared. The severity of skin injury is estimated through clinical PASI scores and histopathological examination. qRT-PCR and multiple cytoline assay were explored to detect the expression levels of cytokines in animal dorsal skin lesions and keratinocyte line HaCaT cells, respectively. The dermis and epidermis of the mouse back were separated for the detection of CCL20 expression. Transcription factor assay was applied to screen, and luciferase activity assay to validate transcription factors regulated by GA. Technology of surface plasmon laser resonance with LC-MS (SPR-MS), molecular docking, and enzyme activity assay were used to identified the target proteins for GA. Finally, we synthesized different derivatives of 18beta-GA and compared their effects, as well as glycyrrhetinic acid (GL), on the skin lesion of imiquimod-induced mice to evaluate the active groups of 18beta-GA. RESULTS: 18ß-glycyrrhetinic acid (GA) improved IMQ-induced psoriatic lesions, and could specifically reduce the chemokine CCL20 level of the epidermis in lesion area, especially in therapeutic administration manner. The process was mainly regulated by transcription factor ATF2 in the keratinocytes. In addition, GUSB was identified as the primary target of 18ßGA. Our findings indicated that the subject on molecular target research of glycyrrhizin should be glycyrrhetinic acid (GA) instead of glycyrrhizic acid (GL), because GL showed little activity in vitro or in vivo. Apart from that, α, ß, -unsaturated carbonyl in C11/12 positions was crucial or unchangeable to its activity of 18ßGA, while proper modification of C3 or C30 position of 18ßGA may vastly increase its activity. CONCLUSION: Our research indicates that 18ßGA exerted its anti-psoriasis effect mainly by suppressing ATF2 and downstream molecule CCL20 predominately through α, ß, -unsaturated carbonyl at C11/12 position binding to GUSB in the keratinocytes, and then broke the feedback loop between keratinocytes and CCR6-expressing immune cells. GA has more advantages than GL in the external treatment of psoriasis. A highlight of this study is to investigate the influence of special active groups on the pharmacological action of a natural product, inspired by the molecular docking result.

Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4.

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.

Do serum vitamin D levels affect assisted reproductive outcomes and perinatal outcomes in young non-PCOS patients? A retrospective study.

PURPOSE: This study aimed to determine the influence of serum vitamin D levels on assisted reproductive and perinatal outcomes in young non-polycystic ovary syndrome (PCOS) patients. METHODS: A total of 3397 non-PCOS women under 35 years who underwent their first IVF/ICSI cycle at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University, from 2018 to 2019, were included. The women were categorized into two groups based on their serum 25(OH)D concentrations: deficient group [25(OH)D < 50 nmol/L] and non-deficient group [25(OH)D ≥ 50 nmol/L]. Ovulation induction results, clinical pregnancy rate, cumulative live birth rate (CLBR), and perinatal outcomes of both groups were compared. RESULTS: A total of 1113 non-PCOS women had successful pregnancies in their first completed IVF cycle. Comparison of laboratory results between the two groups revealed a significantly higher number of oocytes retrieved in the vitamin D-non-deficient group (15.2 ± 6.8 vs. 14.5 ± 6.7, p = 0.015). After controlling for confounding factors, there was no significant difference in the CLBR between the vitamin D-deficient group and the non-deficient group (71.0%, 1,973/2,778 vs. 69.0%, 427/619, p = 0.314, unadjusted). The prevalence of gestational diabetes mellitus (GDM) was higher in the vitamin D-deficient group than in the vitamin D-non-deficient group in both fresh-cycle singleton live births (3.8% vs. 1.2%) and twin live births (2.3% vs. 1.5%). CONCLUSION: This study demonstrated that vitamin D-deficient group had a lower number of oocytes retrieved than the non-deficient group and a higher prevalence of GDM, suggesting that vitamin D deficiency impacts assisted pregnancies and perinatal outcomes in infertile non-PCOS women. However, further studies are required to confirm these findings.

Research progress on ferroptosis in the pathogenesis and treatment of neurodegenerative diseases.

Globally, millions of individuals are impacted by neurodegenerative disorders including Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Although a great deal of energy and financial resources have been invested in disease-related research, breakthroughs in therapeutic approaches remain elusive. The breakdown of cells usually happens together with the onset of neurodegenerative diseases. However, the mechanism that triggers neuronal loss is unknown. Lipid peroxidation, which is iron-dependent, causes a specific type of cell death called ferroptosis, and there is evidence its involvement in the pathogenic cascade of neurodegenerative diseases. However, the specific mechanisms are still not well known. The present article highlights the basic processes that underlie ferroptosis and the corresponding signaling networks. Furthermore, it provides an overview and discussion of current research on the role of ferroptosis across a variety of neurodegenerative conditions.

Radiofrequency radiation reshapes tumor immune microenvironment into antitumor phenotype in pulmonary metastatic melanoma by inducing active transformation of tumor-infiltrating CD8+ T and NK cells.

Immunosuppression by the tumor microenvironment is a pivotal factor contributing to tumor progression and immunotherapy resistance. Priming the tumor immune microenvironment (TIME) has emerged as a promising strategy for improving the efficacy of cancer immunotherapy. In this study we investigated the effects of noninvasive radiofrequency radiation (RFR) exposure on tumor progression and TIME phenotype, as well as the antitumor potential of PD-1 blockage in a model of pulmonary metastatic melanoma (PMM). Mouse model of PMM was established by tail vein injection of B16F10 cells. From day 3 after injection, the mice were exposed to RFR at an average specific absorption rate of 9.7 W/kg for 1 h per day for 14 days. After RFR exposure, lung tissues were harvested and RNAs were extracted for transcriptome sequencing; PMM-infiltrating immune cells were isolated for single-cell RNA-seq analysis. We showed that RFR exposure significantly impeded PMM progression accompanied by remodeled TIME of PMM via altering the proportion and transcription profile of tumor-infiltrating immune cells. RFR exposure increased the activation and cytotoxicity signatures of tumor-infiltrating CD8+ T cells, particularly in the early activation subset with upregulated genes associated with T cell cytotoxicity. The PD-1 checkpoint pathway was upregulated by RFR exposure in CD8+ T cells. RFR exposure also augmented NK cell subsets with increased cytotoxic characteristics in PMM. RFR exposure enhanced the effector function of tumor-infiltrating CD8+ T cells and NK cells, evidenced by increased expression of cytotoxic molecules. RFR-induced inhibition of PMM growth was mediated by RFR-activated CD8+ T cells and NK cells. We conclude that noninvasive RFR exposure induces antitumor remodeling of the TIME, leading to inhibition of tumor progression, which provides a promising novel strategy for TIME priming and potential combination with cancer immunotherapy.

Extracellular volume fraction can predict the treatment response and survival outcome of colorectal cancer liver metastases.

OBJECTIVE: To assess the prognostic value of pre- and post-therapeutic changes in extracellular volume (ECV) fraction of liver metastases (LMs) for treatment response (TR) and survival outcomes in colorectal cancer liver metastases (CRLM). METHODS: 186 LMs were confirmed by pathology or follow-up (Training: 130; Test: 56). We analyzed the changes in ECV fraction of LMs before and after 2 cycles of chemotherapy combined with bevacizumab. After 12 cycles, we evaluated the TR on LMs based on the RECIST v1.1. Relative changes in ECV fraction and Hounsfield Units (HU), defined as ΔECV and ΔHU, were associated with progression-free survival (PFS), overall survival (OS), and TR. We identified TR predictors with multivariate logistic regression and PFS, OS risk factors with COX analysis. RESULTS: 186 LMs were classified as TR lesions (TR+: 84) and non-TR lesions (TR-:102). ΔECV, ΔHUA-E, and texture could distinguish the TR of LMs in training and test set (P < 0.05). ΔECV [Odds ratio (OR): 1.03; 95% Confidence interval (CI): 1.02-1.05, P < 0.01] was an independent predictor of TR-. Area under the curve (AUC), sensitivity and specificity of TR model in training and test set were 0.87, 0.84, 90.14%, 90.32%, 72.88%, 64.00%, respectively. High CRD_score indicates that patients have shorter PFS [Hazard ratio (HR): 2.01; 95%CI: 1.02-3.98, P = 0.045)] and OS (HR: 1.89, 95%CI: 1.04-3.42, P = 0.038). CONCLUSION: ΔECV can be used as an independent predictor of TR of CRLM chemotherapy combined with bevacizumab.

Correlation of CT parameters and PD-L1 expression status in gastric cancer.

OBJECTIVE: We aimed to explore the correlation between routine computed tomography (CT) imaging features and programmed cell death ligand-1(PD-L1) expression status in gastric cancer and evaluate the predictive value of imaging parameters for this immunotherapy biomarker. MATERIALS AND METHODS: Patients with gastric adenocarcinoma who underwent abdominal CT three-stage enhanced scan and PD-L1 immunohistochemical testing before treatment were retrospectively examined. All diagnoses were confirmed through pathology. According to the expression status of PD-L1, they were divided into the positive (CPS ≥ 5) or negative group (CPS < 5). Baseline CT imaging features were collected. Diagnostic performances of the different variables were evaluated using receiver operating characteristic (ROC) curve. RESULTS: In total, 67 patients (17 women and 50 men; mean age: 59.55 ± 10.22 years) with gastric adenocarcinoma were included in the study. The overall stages, probability of maximum lymph node short diameter > 1 cm and peak of lesion enhancement occurring in the arterial phase were statistically significant between the two groups (p < 0.05). Moreover, the arterial enhancement fraction (AEF) was significantly higher in the positive group than that in the negative group (p < 0.05), and ROC curve analysis showed that the AEF exhibited a high evaluation efficacy (area under the curve [AUC] = 0.724 [95% confidence interval (CI): 0.602-0.826]). The combined parameters had the best diagnostic efficacy (AUC = 0.825 [95%CI: 0.716-0.933]), sensitivity (75.00%), and specificity (81.40%). CONCLUSIONS: These findings confirm a correlation between CT imaging features and PD-L1 expression status in gastric cancer, and AEF may help evaluate high PD-L1 expression and select patients suitable for immunotherapy.

Evaluation of flavor substances of rice bran kvass based on electronic nose and gas chromatography-mass spectrometry.

In this paper, the electronic nose (E-nose) and headspace-solid phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS) were used to analyze the volatiles of rice bran kvass (RBK) with the reference of Qiulin kvass (QLK). Meanwhile, the flavor amino acids of RBK before and after fermentation were determined. The results showed that the kinds of kvass remained consistent in terms of the overall category of volatiles while there were differences in content between them (p < 0.05). A total of 35 volatile compounds, mainly including esters, alcohols, phenols, aldehydes, and acids, were identified by GC-MS in the two kinds of kvass. In addition, the total essential amino acid content and the total sweet amino acid content of RBK increased significantly (p < 0.05) after fermentation. RBK contains both the main flavor of kvass and its own unique characteristics, making it a new member of the Kvass family.

Transient-State Self-Bipolarized Organic Frameworks of Single Aromatic Units for Natural Sunlight-Driven Photosynthesis of H2 O2.

Constructing π-conjugated polymer structures through covalent bonds dominates the design of organic framework photocatalysts, which significantly depends on the selection of multiple donor-acceptor building blocks to narrow the optical gap and increase the lifetimes of charge carriers. In this work, self-bipolarized organic frameworks of single aromatic units are demonstrated as novel broad-spectrum-responsive photocatalysts for H2 O2 production. The preparation of such photocatalysts is only to fix the aromatic units (such as 1,3,5-triphenylbenzene) with alkane linkers in 3D space. Self-bipolarized aromatic units can drive the H2 O2 production from H2 O and O2 under natural sunlight, wide pH ranges (3.0-10.0) and natural water sources. Moreover, it can be extended to catalyze the oxidative coupling of amines. Experimental and theoretical investigation demonstrate that such a strategy obeys the mechanism of through-space π-conjugation, where the closely face-to-face overlapped aromatic rings permit the electron and energy transfer through the large-area delocalization of the electron cloud under visible light irradiation. This work introduces a novel design concept for the development of organic photocatalysts, which will break the restriction of conventional through-band π-conjugation structure and will open a new way in the synthesis of organic photocatalysts.

Photocatalytic Proton-Coupled Electron Transfer Enabled Radical Cyclization for Isoquinoline-1,3-diones Synthesis.

Radical cyclization has been demonstrated to be an efficient method to access functionalized heterocycles from easily accessible raw materials. Described herein is the development of a photocatalytic proton-coupled electron transfer (PCET) strategy for the synthesis of isoquinoline-1,3-diones using readily prepared naphthalimide (NI)-based organic photocatalysts. The process features free metal-complex photocatalysts, acids, and mild reaction conditions. This mild radical cyclization protocol has a broad substrate scope and can be effectively applied to a variety of medicinally relevant substrates. Furthermore, control experiments were conducted to elucidate the mechanism of this visible light-induced methodology.