Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes.

Deletion of master regulators of the B cell lineage reprograms B cells into T cells. Here we found that the transcription factor Hoxb5, which is expressed in uncommitted hematopoietic progenitor cells but is not present in cells committed to the B cell or T cell lineage, was able to reprogram pro-pre-B cells into functional early T cell lineage progenitors. This reprogramming started in the bone marrow and was completed in the thymus and gave rise to T lymphocytes with transcriptomes, hierarchical differentiation, tissue distribution and immunological functions that closely resembled those of their natural counterparts. Hoxb5 repressed B cell 'master genes', activated regulators of T cells and regulated crucial chromatin modifiers in pro-pre-B cells and ultimately drove the B cell fate-to-T cell fate conversion. Our results provide a de novo paradigm for the generation of functional T cells through reprogramming in vivo.

Publisher Correction: Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes.

In the version of this article initially published, some identification of the supplementary information was incorrect. The items originally called Supplementary Tables 1, 2, 3, 4 and 5 should be Source Data Figures 1, 2, 4, 5 and 7, respectively; those originally called Supplementary Tables 6, 7 and 8 should be Supplementary Tables 1, 2 and 3, respectively; and those originally called Source Data Figures 1, 2, 4, 5 and 7 should be Supplementary Tables 4, 5, 6, 7 and 8, respectively. The errors have been corrected in the HTML version of the article.

Ligand Defect-Induced Active Sites in Ni-MOF-74 for Efficient Photocatalytic CO2 Reduction to CO.

The conversion of CO2 into valuable carbon-based products using clean and renewable solar energy has been a significant challenge in photocatalysis. It is of paramount importance to develop efficient photocatalysts for the catalytic conversion of CO2 using visible light. In this study, the Ni-MOF-74 material is successfully modified to achieve a highly porous structure (Ni-74-Am) through temperature and solvent modulation. Compared to the original Ni-MOF-74, Ni-74-Am contains more unsaturated Ni active sites resulting from defects, thereby enhancing the performance of CO2 photocatalytic conversion. Remarkably, Ni-74-Am exhibits outstanding photocatalytic performance, with a CO generation rate of 1380 µmol g-1 h-1 and 94% CO selectivity under visible light, significantly surpassing the majority of MOF-based photocatalysts reported to date. Furthermore, experimental characterizations reveal that Ni-74-Am has significantly higher efficiency of photogenerated electron-hole separation and faster carrier migration rate for photocatalytic CO2 reduction. This work enriches the design and application of defective MOFs and provides new insights into the design of MOF-based photocatalysts for renewable energy and environmental sustainability. The findings of this study hold significant promise for developing efficient photocatalysts for CO2 reduction under visible-light conditions.

Changes in microbial composition and interaction patterns of female urogenital tract and rectum in response to HPV infection.

BACKGROUND: Previous studies have shown that changes in the microbial community of the female urogenital tract are associated with Human papillomavirus (HPV) infection. However, research on this association was mostly focused on a single site, and there are currently few joint studies on HPV infection and multiple sites in the female urogenital tract. METHODS: We selected 102 healthy women from Yunnan Province as the research object, collected cervical exfoliation fluid, vaginal, urethral, and rectal swabs for microbial community analysis, and measured bacterial load, and related cytokine content. The link between HPV, microbiota, and inflammation was comprehensively evaluated using bioinformatics methods. FINDINGS: The impact of HPV infection on the microbial composition of different parts varies. We have identified several signature bacterial genera that respond to HPV infection in several detection sites, such as Corynebacterium, Lactobacillus, Campylobacter, and Cutibacterium have been detected in multiple sites, reflecting their potential significance in cross body sites HPV infection responses. There was a solid microbial interaction network between the cervix, vagina, and urethra. The interrelationships between inflammatory factors and different bacterial genera might also affect the immune system's response to HPV infection. INTERPRETATION: It might be an effective strategy to prevent and treat HPV infection by simultaneously understanding the correlation between the microbial changes in multiple parts of the female urogenital tract and rectum and HPV infection, and controlling the microbial network related to HPV infection in different parts.

Understanding the mechanism of safety attitude mitigates the turnover intention novice nurses via the person-centred method: A theory-driven, deductive cross-sectional study.

AIM: Examine profiles of safety attitudes among novices and explore whether profiles moderate the occupational identity-turnover pathway. BACKGROUND: Novice nurses face unique challenges in adopting positive safety attitudes, which influence outcomes like turnover. However, past research found only average levels of safety attitudes among novices, ignoring possible heterogeneity. Exploring whether meaningful subgroups exist based on safety perspectives and factors shaping them can provide insights to improve safety attitudes and retention. DESIGN: This study was designed as a cross-sectional investigation. METHODS: Data were collected through the distribution of questionnaires. Descriptive statistics were first conducted, followed by latent profile analysis. We then carried out univariate analysis and ordinal multinomial regression to explore the factors shaping the different profiles. Finally, we examine the moderating effect of nurses' safety attitudes with different latent profiles on the relationship between professional identification and turnover intention. RESULTS: A total of 816 novice nurses were included. Three profiles were identified: high, moderate and low safety attitudes - higher attitudes were associated with lower turnover intention. Interest in nursing, health status, identity and turnover predicted profile membership. Moderate profile had a stronger buffering effect on the identity-turnover link versus high profile. CONCLUSION: Multiple safety attitude profiles exist among novice nurses. Certain factors like interest in nursing and occupational identity are associated with more positive safety profiles. Targeting these factors could potentially improve safety attitudes and reduce turnover among novice nurses. The moderating effects suggest that tailored interventions matching specific subgroups may maximize impact. IMPACT: Assessing subgroup attitudes enables tailored training for novices' specific needs, nurturing continuous improvement. Supporting early career development and role identity may strengthen retention intentions.

Improving the Encapsulation Efficiency of Lipase in Molecular Cages and Its Application.

Here, lipase encapsulation is constructed by locking enzyme molecules in nanomolecular cages on the surface of SH-PEI@PVAC magnetic microspheres. To improve the encapsulation efficiency in enzyme loading, the thiol group is efficiently modified on the grafted polyethyleneimine (PEI) using 3-mercaptopropionic acid. N2 adsorption-desorption isotherms reveal the existence of mesoporous molecular cages on the microsphere surface. The robust immobilizing strength of carriers to lipase demonstrates the successful encapsulation of enzymes in nanomolecular cages. The encapsulated lipase shows high enzyme loading (52.9 mg/g) and high activity (51.4 U/mg). Different sizes of molecular cages are established, and the cage size showed important effects on lipase encapsulation. It shows that enzyme loading is low at a small size of molecular cages, which is attributed to that the nanomolecular cage is too small to house lipase. The investigation in lipase conformation suggests that the encapsulated lipase retains its active conformation. Compared with the adsorbed lipase, the encapsulated lipase shows higher thermal stability (4.9 times) and higher resistance to denaturants (5.0 times). Encouragingly, the encapsulated lipase shows high activity and reusability in lipase-catalyzed synthesis of propyl laurate, suggesting the potential application value of encapsulated lipase.

Virtual screening of novel mTOR inhibitors for the potential treatment of human colorectal cancer.

The abnormal activation of the mTOR pathway is closely related to the occurrence and progression of cancer, especially colorectal cancer. In this study, a rational virtual screening strategy has been established and MT-5, a novel mTOR inhibitor with a quinoline scaffold, was obtained from the ChemDiv database. MT-5 showed potent kinase inhibitory activity (IC50: 8.90 µM) and antiproliferative effects against various cancer cell lines, especially HCT-116 cells (IC50: 4.61 µM), and this was 2.2-fold more potent than that of the cisplatin control (IC50: 9.99 µM). Western blot, cell migration, cycle arrest, and apoptosis assays were performed with HCT-116 cells to investigate the potential anticancer mechanism of MT-5. Metabolic stability results in vitro indicated that MT-5 exhibited good stability profiles in artificial gastrointestinal fluids, rat plasma, and liver microsomes. In addition, the key contribution of the residues around the binding pocket of MT-5 in binding to the mTOR protein was also investigated from a computational perspective.

The association of air pollutants with hospital outpatient visits for child and adolescence psychiatry in Shenzhen, China.

BACKGROUND: Although exposure to ambient air pollution has been associated with mental disorder, little is known about its potential effects on children and adolescents, especially in Chinese population. We aimed to reveal the relationship of air pollutants with hospital outpatient visits for child and adolescence psychiatry (HOVCAP) in Shenzhen. METHODS: A case-crossover study based on time-series data was applied, and a distributed lag non-linear model (DLNM) was used to evaluate the non-linear and delayed effects of 4 major air pollutants (NO2, PM2.5, SO2 and O3) on HOVCAP. Least absolute shrinkage and selection operator (LASSO) regression was used to control the multicollinearity between covariates and to filter variables. RESULT: A total of 94,660 cases aged 3-18 were collected from 2014 to 2019 in the Mental Health Center of Shenzhen. Results of pollutants at mode value (M0) showed that in the single lag effect result, when the average daily concentration of NO2 at 24 µg/m3, there was a significant effect on HOVCAP over lag 1, lag 4 and lag 5, respectively. The cumulative RR of NO2 M0 value to the outpatient visits were 1.438 (1.137-1.818) over lag 0-2, 1.454 (1.120-1.887) over lag 0-3, 1.466 (1.084-1.982) over lag 0-4, 1.680 (1.199-2.354) over lag 0-5, 1.993 (1.369-2.903) over lag 0-6, and 2.069 (1.372-3.119) over lag 0-7. However, PM2.5, SO2, O3 were not associated with HOVCAP over neither single lag effects nor cumulative effects. The RR values both shown an increase either when NO2 increases by 10 units or when the maximum concentration of NO2 is reached. CONCLUSION: Our study suggests that exposure to the normal air quality of NO2 in Shenzhen may associated with the risk of HOVCAP. However, PM2.5, SO2, O3 were not associated with HOVCAP.

A Network Pharmacology and Multi-Omics Combination Approach to Reveal the Effect of Strontium on Ca2+ Metabolism in Bovine Rumen Epithelial Cells.

Strontium (Sr) belongs to the same group in the periodic table as calcium (Ca). Sr level can serve as an index of rumen Ca absorption capacity; however, the effects of Sr on Ca2+ metabolism are unclear. This study aims to investigate the effect of Sr on Ca2+ metabolism in bovine rumen epithelial cells. The bovine rumen epithelial cells were isolated from the rumen of newborn Holstein male calves (n = 3, 1 day old, 38.0 ± 2.8 kg, fasting). The half maximal inhibitory concentration (IC50) of Sr-treated bovine rumen epithelial cells and cell cycle were used to establish the Sr treatment model. Transcriptomics, proteomics, and network pharmacology were conducted to investigate the core targets of Sr-mediated regulation of Ca2+ metabolism in bovine rumen epithelial cells. The data of transcriptomics and proteomics were analyzed using bioinformatic analysis (Gene Ontology and Kyoto Encyclopedia of genes/protein). Quantitative data were analyzed using one-way ANOVA in GraphPad Prism 8.4.3 and the Shapiro-Wilk test was used for the normality test. Results presented that the IC50 of Sr treatment bovine rumen epithelial cells for 24 h was 43.21 mmol/L, and Sr increased intracellular Ca2+ levels. Multi-omics results demonstrated the differential expression of 770 mRNAs and 2436 proteins after Sr treatment; network pharmacology and reverse transcriptase polymerase chain reaction (RT-PCR) revealed Adenosylhomocysteine hydrolase-like protein 2 (AHCYL2), Semaphoring 3A (SEMA3A), Parathyroid hormone-related protein (PTHLH), Transforming growth factor ß2 (TGF-ß2), and Cholesterol side-chain cleavage enzyme (CYP11A1) as potential targets for Sr-mediated Ca2+ metabolism regulation. Together these results will improve the current comprehension of the regulatory effect of Sr on Ca2+ metabolism and pave a theoretical basis for Sr application in bovine hypocalcemia.

Modeling of NO mass transfer characteristics absorbed in sodium persulfate solution with a bubble reactor.

Sodium persulfate solution is considered as an effective wet denitrification medium, however, it is unclear that the influence of the operating conditions on mass transfer characteristics parameters during the absorption of NO with sodium persulfate solution. To determine the key mass transfer characteristics parameters, the specific interfacial area a and the mass transfer coefficients kL,  kG, were determined based on the Danckwerts method during CO2 absorption in a bubble column. kL, kG  and a were calculated by correlations between the mass transfer coefficients of NO and CO2. Results showed that the specific interfacial area increased 77.64 m-1, the liquid phase mass transfer coefficient increased 2.49 × 10-4 m·s-1, and the gas phase mass transfer coefficient increased 0.71 × 10-5 mol·Pa-1·s-1·m-2 with superficial gas velocity increasing from 0.6 to 1.4 L·min-1. With the temperature of sodium persulfate solution increasing from 293 to 333 K, the specific interfacial area decreased 42.66 m-1, while the liquid phase mass transfer coefficient and the gas phase mass transfer coefficient increased 3.89 × 10-4 m·s-1 and 1.18 × 10-5 mol·Pa-1·s-1·m-2, respectively. The experiments results determined the correlations of a, kL, and kG  with the temperature of the absorption phase and the superficial velocity of the gas. It can serve as a guide to the enhancement of the sodium persulfate wet denitrification process.

Loss of Nupr1 promotes engraftment by tuning the quiescence threshold of hematopoietic stem cell repository via regulating p53-checkpoint pathway.

Hematopoietic stem cells (HSCs) are dominantly quiescent under homeostasis, which is a key mechanism of maintaining the HSC pool for life-long hematopoiesis. Dormant HSCs poise to be immediately activated on urgent conditions and can return to quiescence after regaining homeostasis. To date, the molecular networks of regulating the threshold of HSC dormancy, if exist, remain largely unknown. Here, we unveiled that deletion of Nupr1, a gene preferentially expressed in HSCs, activated the quiescence HSCs under homeostatic status, which conferred engraftment competitive advantage on HSCs without compromising their stemness and multi-lineage differentiation abilities in serial transplantation settings. Following an expansion protocol, the Nupr1-/- HSCs proliferate more robustly than their wild type counterparts in vitro. Nupr1 inhibits the expression of p53 and the rescue of which offsets the engraftment advantage. Our data unveil the de novo role of Nupr1 as an HSC quiescence-regulator, which provides insights into accelerating the engraftment efficacy of HSC transplantation by targeting the HSC quiescence-controlling network.

Cerebral infarct induced by severe leptospirosis-a case report and literature review.

BACKGROUND: Although most leptospirosis is mild, the severe form can cause multiple complications, with a fatality rate of over 50% even with ICU support. The clinical manifestations of leptospirosis vary depending on organs and tissues involved. Both cerebral artery and coronary artery can be damaged by leptospirosis. Although cerebral arteritis induced by leptospirosis has been reported, cerebral infarction caused by leptospirosis is rarely reported. CASE PRESENTATION: We report the case of a 79-year-old man admitted to intensive care unit (ICU) because of 3 days duration of fever, bloody sputum and dyspnea. Five days before he was admitted to hospital, he had harvested rice in flooded fields. After admission, leptospira interrogans DNA sequence was identified in bronchoalveolar lavage fluid (BALF) by next-generation sequencing (NGS). Microscopic agglutination test (MAT) showed the serum antibody of Mini serovars was 1,600 and Hebdomadis serovars was 800. On the eighth day of admission, the patient noted left hemiplegia. Cranial CT scan revealed low-density shadow in the right basal ganglia, so cerebral infarction was diagnosed. The patient's condition rapidly deteriorated and he died on the eleventh day of admission despite penicillin treatment, invasive mechanical ventilation and continuous renal replacement support. CONCLUSION: Neurologic leptospirosis manifested as cerebral occlusion, although rare, might be deadly and should not be ignored.

Cobalt-promoted synthesis of sulfurated oxindoles via radical annulation of N-arylacrylamides with disulfides.

An efficient radical annulation of N-arylacrylamides with disulfides is developed for the synthesis of sulfurated oxindoles. The reaction occurs in a facile manner using CoBr2 as both an initiator and a promoter for the first time and (NH4)2S2O8 as the oxidant. By controlling the CoBr2/(NH4)2S2O8 ratio, a wide range of sulfurated and brominated/sulfurated oxindoles are selectively prepared in good to excellent yields. The present protocol is simple and highly atom economical, and can tolerate a broad range of substrates.

Associations among health-promoting lifestyle, self-care agency and health-related quality of life in Bai older adults with hypertension in Yunnan China.

BACKGROUND: Previous Chinese studies focused on the prevalence and influential factors of hypertension; however, little is known about their self-care literacy and quality of life among the Bai older adults with hypertension. The purpose of this research was to explore the associations among health-promoting lifestyle, self-care agency, and health-related quality of life in Bai ethnic older patients with hypertension, as well as the related factors of hypertension self-care abilities. METHODS: A total of 472 Bai ethnic hypertension older adults aged 60 and above were enrolled in this study voluntarily from 5 rural communities of the Bai ethnic group. The Exercise of Self-Care Agency Scale (ESCAS) was employed to assess the Self-care ability of hypertension for the subjects, the Health-promoting lifestyle profile II(HPLP-II) was utilized to evaluate the health behavior, and MOS 36-Item Short Form Health Survey (SF-36) was chosen to assess the HRQOL for the studying population. All descriptive analyses, including demographic characteristics, socio-economic status, and clinical characteristics were stratified by Bai hypertensive elderly. Pearson correlation analysis model was used to examine the associations among health-promoting lifestyle, self-care agency, and health-related quality of life in Bai ethnic elderly with hypertension. RESULTS: The HPLP-II, ESCA, and of HRQOL levels of the subjects were low, and the mean HPLP and ESCA scores had no significant statistical variance among different age groups. Significant statistical differences were found in Bai elderly subjects in the domain of PF and PH as well as the overall score in SF-36(all P< 0.01), 60-64 year group had the highest score of the above three domains in SF-36 than other age groups. The SF-36 scores were positively associated with HPLP and ESCA levels. CONCLUSION: The HPLP-II, ESCA, and of HRQOL levels of the Bai subjects were poor in the Bai ethnic hypertensive elderly. The HRQOL scores of subjects were positively connected with HPLP-II and ESCA abilities. More attention should be paid to lifestyle, healthy behaviors, and self-care abilities improvements to enhance the better HRQOL of Bai minority older adults with hypertension.

A Deep Learning-based Method to Extract Lumen and Media-Adventitia in Intravascular Ultrasound Images.

Intravascular ultrasound (IVUS) imaging allows direct visualization of the coronary vessel wall and is suitable for assessing atherosclerosis and the degree of stenosis. Accurate segmentation and lumen and median-adventitia (MA) measurements from IVUS are essential for such a successful clinical evaluation. However, current automated segmentation by commercial software relies on manual corrections, which is time-consuming and user-dependent. We aim to develop a deep learning-based method using an encoder-decoder deep architecture to automatically and accurately extract both lumen and MA border. Inspired by the dual-path design of the state-of-the-art model IVUS-Net, our method named IVUS-U-Net++ achieved an extension of the U-Net++ model. More specifically, a feature pyramid network was added to the U-Net++ model, enabling the utilization of feature maps at different scales. Following the segmentation, the Pearson correlation and Bland-Altman analyses were performed to evaluate the correlations of 12 clinical parameters measured from our segmentation results and the ground truth. A dataset with 1746 IVUS images from 18 patients was used for training and testing. Our segmentation model at the patient level achieved a Jaccard measure (JM) of 0.9080 ± 0.0321 and a Hausdorff distance (HD) of 0.1484 ± 0.1584 mm for the lumen border; it achieved a JM of 0.9199 ± 0.0370 and an HD of 0.1781 ± 0.1906 mm for the MA border. The 12 clinical parameters measured from our segmentation results agreed well with those from the ground truth (all p-values are smaller than .01). Our proposed method shows great promise for its clinical use in IVUS segmentation.

Relationship between Brain Metabolic Disorders and Cognitive Impairment: LDL Receptor Defect.

The low-density-lipoprotein receptor (LDLr) removes low-density lipoprotein (LDL), an endovascular transporter that carries cholesterol from the bloodstream to peripheral tissues. The maintenance of cholesterol content in the brain, which is important to protect brain function, is affected by LDLr. LDLr co-localizes with the insulin receptor and complements the internalization of LDL. In LDLr deficiency, LDL blood levels and insulin resistance increase, leading to abnormal cholesterol control and cognitive deficits in atherosclerosis. Defects in brain cholesterol metabolism lead to neuroinflammation and blood-brain-barrier (BBB) degradation. Moreover, interactions between endoplasmic reticulum stress (ER stress) and mitochondria are induced by ox-LDL accumulation, apolipoprotein E (ApoE) regulates the levels of amyloid beta (Aß) in the brain, and hypoxia is induced by apoptosis induced by the LDLr defect. This review summarizes the association between neurodegenerative brain disease and typical cognitive deficits.

Utility of Exosomes in Ischemic and Hemorrhagic Stroke Diagnosis and Treatment.

Stroke is the leading cause of death and neurological disorders worldwide. However, diagnostic techniques and treatments for stroke patients are still limited for certain types of stroke. Intensive research has been conducted so far to find suitable diagnostic techniques and treatments, but so far there has been no success. In recent years, various studies have drawn much attention to the clinical value of utilizing the mechanism of exosomes, low toxicity, biodegradability, and the ability to cross the blood-brain barrier. Recent studies have been reported on the use of biomarkers and protective and recovery effects of exosomes derived from stem cells or various cells in the diagnostic stage after stroke. This review focuses on publications describing changes in diagnostic biomarkers of exosomes following various strokes and processes for various potential applications as therapeutics.

Hypoxia-induced CNPY2 upregulation promotes glycolysis in cervical cancer through activation of AKT pathway.

This study aimed to investigate the function and mechanism of the protein-coding gene CNPY2 in the glycolysis of cervical cancer cells. Cells were exposed to normoxia and hypoxia conditions. Knockdown and ectopic overexpression of CNPY2 were achieved by transfection of small interfering RNA (siRNA) specific to CNPY2 or CNPY2 overexpression vectors, respectively. Quantitative real-time PCR and Western blot were used to evaluate CNPY2 expression in patient specimens and different cervical cancer cell lines under normoxia or hypoxia conditions. Cell viability was assessed by MTT and colony formation assays. Glucose consumption, lactate production, oxygen consumption and ATP production were analyzed by enzyme-linked immunosorbent assays. Dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed to detect interaction between hypoxia-induced factor 1α (HIF-1α) on CNPY2 promoter. CNPY2 upregulation was a characteristic of cervical cancer and correlated with poor prognosis. Knockdown and overexpression of CNPY2 inhibited and promoted proliferation glucose consumption, lactate production, oxygen consumption and ATP production in cervical cancer cells, respectively. CNPY2 was transcriptionally regulated by HIF-1α. The hypoxia-induced "Warburg effect" in cervical cancer cells was at least partially dependent on the CNPY2/AKT signaling pathway. Hypoxia-induced CNPY2 promoted glycolysis in cervical cancer cells by activating the AKT pathway. CNPY2 may serve as a potential diagnostic marker and therapeutic target for cervical cancer patients.

circ-PTK2 (hsa_circ_0008305) regulates the pathogenic processes of ovarian cancer via miR-639 and FOXC1 regulatory cascade.

BACKGROUND: Precise quantification of microRNA is challenging since circulating mRNA and rRNA in the blood are usually degraded. Therefore, it is necessary to identify specific biomarkers for ovarian cancer. This study aimed to investigate candidate circular RNAs (circRNAs) involved in the pathogenic process of ovarian cancer after inhibition of chromodomain helicase DNA binding protein 1-like (CHD1L) and the corresponding mechanism. METHODS: CHD1L mRNA-targeted siRNA was designed and induced a decreased level of CHD1L function in SK-OV-3 and OVCAR-3 cells observed via transwell and wound healing assays and assessment of epithelial-mesenchymal transition (EMT)-related protein expression by immunofluorescence (IF) and western blotting (WB). After decreasing the level of CHD1L, RNA-seq was conducted, and the circRNA expression profiles were obtained. cirRNAs were then selected and validated by PCR together with Sanger sequencing, fluorescent in situ hybridization (FISH), and reverse transcriptase-quantitative PCR (RT-qPCR). Selected circRNA function in vitro was adjusted via interference and overexpression and assessed via transwell assay, tube formation, and EMT-related protein assay by IF and WB; tumor formation in vivo was followed via hematoxylin and eosin (HE) staining and immunohistochemistry of EMT-related proteins. Based on the competing endogenous RNA prediction of circRNA targets, candidate miRNAs were found, and their downstream mRNAs targeted by the selected miRNA were identified and validated by luciferase assay. The functions of these selected miRNA and mRNA were then further investigated through transwell and WB assay of EMT-related proteins. RESULTS: CHD1L was significantly upregulated in ovarian cancer tissues and patients with higher expression of CHD1L had a shorter relapse-free survival (P < 0.001) and overall survival (P < 0.001). Inhibiting the level of CHD1L significantly decreased cell migration and invasion (P < 0.05), increased the expression of epithelial markers, and decreased the expression of mesenchymal markers. Following inhibition of CHD1L expression, RNA-seq was conducted and 82 circRNAs had significantly upregulated expression, while 247 had significantly downregulated expression. The circRNAs were validated by PCR, and hsa_circ_0008305 (circ-PTK2) was selected and further validated by Sanger sequencing, FISH, and RT-qPCR. Circ-PTK2 expression was significantly higher in the ovarian cancer tissues compared with normal ovary tissues (P < 0.001). By regulating the level of circ-PTK2 with siRNA and an overexpression vector, expression of circ-PTK2 was found to be positively correlated to cell migration and invasion. Overexpression of circ-PTK2 enhanced tumor formation and was correlated to expression of EMT pathway markers. Prediction of the target of circ-PTK2 was validated with dual luciferase assay and identified miR-639 and FOXC1 as the valid target of circ-PTK2 and miR-639, respectively. The RNA level of miR-639 was negatively correlated to cell proliferation and migration, whereas the mRNA level of FOXC1 was positively correlated to those processes. miR-639 mimics reversed the function of circ-PTK2 overexpression; however, interference of FOXC1 mRNA also reversed the function of circ-PTK2. CONCLUSIONS: circ-PTK2 is an important molecule in regulating the pathogenic processes of ovarian cancer via the miR-639 and FOXC1 regulatory cascade.

Iron-Catalyzed Radical Annulation of Unsaturated Carboxylic Acids with Disulfides for the Synthesis of γ-Lactones.

An efficient aerobic iron-catalyzed annulation of unsaturated carboxylic acids with disulfides has been developed. This procedure proceeds using FeCl3 as the catalyst and KI as an iodine source under an air atmosphere, which provides practical access to a wide range of substituted γ-lactone derivatives. The disclosed method is quite simple, highly atom-economic, environmentally friendly, and tolerates a broad substrate scope.