Incomplete retinal vascularization with retinopathy of prematurity-like ridges in healthy full-term newborns.

PURPOSE: To describe the characteristics and clinical course of retinopathy of prematurity (ROP)-like ridges in healthy full-term newborns. METHODS: A retrospective medical record review was performed on newborns who underwent fundus photography within 72 h of birth between January 1st and December 31st, 2019 at Women & Children's Health Care Hospital of Huantai, China. The RetCam 3 wide-field digital imaging system was used for fundus photography. ROP-like ridges were discovered and described. RESULTS: Total of 5507 full-term infants underwent fundus photography. ROP-like ridges were discovered in 90 eyes from 57 infants (1.0%). Stage 1 ROP-like was seen in 63 of the eyes (70%), Stage 2 ROP-like in 26 of the eyes (28.9%), and Stage 3 ROP-like in 1 eye (1.1%). These ROP-like ridges were found in Zone II (41.1%) and Zone III (58.9%), but not in Zone I. Eight (8.9%) of the eyes had pre-plus-like diseases. No eyes had plus disease. All ROP-like ridges and pre-plus-like diseases were spontaneously regressed with a mean duration of 39.0 ± 8.2 days. Male sex (P = 0.003) was positively associated with ROP-like changes. CONCLUSION: Healthy full-term newborns may have incomplete retinal vascularization and ROP-like ridges at birth. These ROP-like ridges showed signs of spontaneous regression.

Long Non-Coding RNA LINC00052 Targets miR-548p/Notch2/Pyk2 to Modulate Tumor Budding and Metastasis of Human Breast Cancer.

Abnormal expression of long non-coding RNAs (lncRNAs) is involved in many pathological processes of cancers. However, the role of lncRNA LINC00052 in breast cancer progression is still unclear. Here, LINC00052 expression was detected by in situ hybridization and quantitative real-time PCR assays. Cell Counting Kit-8, wound healing, and transwell assays were used to investigate changes in the proliferation, migration, and invasion of breast cancer cells. MiR-548p was found associated with LINC00052 or Notch2 by RNA pull-down, dual-luciferase reporter, and qRT-PCR assays. The effect of LINC00052 on lung metastasis was explored through in vivo experiments. High LINC00052 expression was observed in breast cancer tissues and cells. LINC00052 silencing inhibited the proliferation, migration, and invasion of MCF7 cells, and LINC00052 overexpression produced the opposite results. MiR-548p, a target gene of LINC00052, partially rescued the effects of LINC00052 on proliferation, migration, and invasion of MCF7. Notch2 was the target of miR-548p and LINC00052 could promote Notch2 expression. Moreover, the phosphorylation of proline-rich tyrosine kinase 2 (Pyk2), a downstream factor of Notch2, was increased by LINC00052, and a Pyk2 mutant could inhibit the cell migration and invasion induced by LINC00052 overexpression in MDA-MB-468 cells, which was similar to the function of the miR-548p mimic. We further demonstrated that LINC00052 exacerbated the metastases of breast cancer cells in vivo. Our research demonstrated that LINC00052 is highly expressed in breast cancer and promotes breast cancer proliferation, migration, and invasion via the miR-548p/Notch2/Pyk2 axis. LINC00052 could serve as a potential therapeutic target for breast cancer.

Aptamer-mediated hollow MnO2 for targeting the delivery of sorafenib.

Sorafenib (SRF) presents undesirable effects in clinical treatment, due to the lack of targeting, poor water solubility, and obvious side effects. In this study, we constructed a novel nanodrug carrier system for accurate and efficient delivery of SRF, improving its therapeutic effects and achieving tumor-specific imaging. The hollow mesoporous MnO2 (H-MnO2) nanoparticles equipped with target substance aptamers (APT) on the surface were used to load SRF for the first time. The resulting H-MnO2-SRF-APT could specifically bound to glypican-3 (GPC3) receptors on the surface of hepatocellular carcinoma (HCC), rapidly undergoing subsequent degradation under decreased pH conditions in the tumor microenvironment (TME) and releasing the loaded SRF. In this process, Mn2+ ions were used for T1-weighted magnetic resonance imaging simultaneously. The in vitro cell experiments indicated that H-MnO2-SRF-APT showed much more effects on the inhibition in the proliferation of Huh7 and HepG2 HCC cells than that of the non-targeted H-MnO2-SRF and free SRF. Besides, the in vivo results further confirmed that H-MnO2-SRF-APT could effectively inhibit the growth of xenograft tumors Huh7 in the naked mouse with good biosafety. In conclusion, H-MnO2-SRF-APT could significantly enhance the therapeutic effect of SRF and is expected to be a new way of diagnosis and treatment of HCC.

Inhibitor of glutamine metabolism V9302 promotes ROS-induced autophagic degradation of B7H3 to enhance antitumor immunity.

Despite the enormous successes of anti-PD-1/PD-L1 immunotherapy in multiple other cancer types, the overall response rates of breast cancer remain suboptimal. Therefore, exploring additional immune checkpoint molecules for potential cancer treatment is crucial. B7H3, a T-cell coinhibitory molecule, is specifically overexpressed in breast cancer compared with normal breast tissue and benign lesions, making it an attractive therapeutic target. However, the mechanism by which B7H3 contributes to the cancer phenotype is unclear. Here we show that the expression of B7H3 is negatively related to the number of CD8+ T cells in breast tumor sites. In addition, analysis of the differentially expressed B7H3 reveals that it is inversely correlated to autophagic flux both in breast cancer cell lines and clinical tumor tissues. Furthermore, block of autophagy by bafilomycin A1 (Baf A1) increases B7H3 levels and attenuates CD8+ T cell activation, while promotion of autophagy by V9302, a small-molecule inhibitor of glutamine metabolism, decreases B7H3 expression and enhances granzyme B (GzB) production of CD8+ T cells via regulation of reactive oxygen species (ROS) accumulation. We demonstrate that combined treatment with V9302 and anti-PD-1 monoclonal antibody (mAb) enhances antitumor immunity in syngeneic mouse models. Collectively, our findings unveil the beneficial effect of V9302 in boosting antitumor immune response in breast cancer and illustrate that anti-PD-1 together with V9302 treatment may provide synergistic effects in the treatment of patients insensitive to anti-PD-1 therapy.

Do governmental policy interventions help urban economic recovery? Experimental evidence from China's provinces governance amid the COVID-19 pandemic.

By examining China's province-level data, this paper uses governmental intervention theory to investigate the extent to which governmental policy interventions alleviate the impact of the COVID-19 pandemic on local economic growth. Results suggest that stronger government intervention during COVID-19 pandemic boost the economic recovery, and the effectiveness of governmental policy interventions is contingent on pandemic severity and local economic endowment. Specifically, facilitating effect of government intervention on economic growth is effective in all provinces, and the impact of government intervention is more pronounced in the province with more diagnosed cases, a high level of marketization and fiscal income.

Retraction Note to: Anticancer effects of ovatodiolide on human prostate cancer cells involves cell cycle arrest, apoptosis and blocking of Ras/Raf/MEK/ERK signaling pathway.

Retraction of "Anticancer effects of ovatodiolide on human prostate cancer cells involves cell cycle arrest, apoptosis and blocking of Ras/Raf/MEK/ERK signaling pathway", by Dongsheng Jia, Jianbo Zheng, Junli Yu, Ning Zhao, Shengxing Lu, Dongfang Hao. JBUON 2020;25(5):2412-2417; PMID: 33277863 Following the publication of the above article, readers drew to our attention that part of the data was unreliable: Figures of this article appeared in other articles (by totally different authors). The authors were requested to provide the raw data and were also asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. Given above, we decided to retract this article. Authors were informed of the retraction. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

Efficient degradation of ciprofloxacin by magnetic γ-Fe2O3-MnO2 with oxygen vacancy in visible-light/peroxymonosulfate system.

In this work, the magnetic γ-Fe2O3-MnO2 bifunctional catalyst with oxygen vacancy was synthesized for peroxymonosulfate (PMS) activation under visible light. The activity of γ-Fe2O3-MnO2 was investigated by ciprofloxacin (cipro) degradation. Results showed that 98.3% of cipro (50 µM) was removed within 30 min in visible-light/PMS system mediated by γ-Fe2O3-MnO2 (2:1) with fine-tuned oxygen vacancy. The cipro degradation data fitted well with pseudo-first-order kinetic model with the highest kinetic constant of 0.114 min-1. Besides, the γ-Fe2O3-MnO2 exhibited stability, recyclability and practicability. High selectivity for cipro degradation was observed with coexisting anions in visible-light/γ-Fe2O3-MnO2/PMS system. Furthermore, the enhanced mechanism of PMS activation under visible light with γ-Fe2O3-MnO2 was proposed. The appropriate oxygen vacancy enhanced the separation of photo-induced carriers and Z scheme heterostructure maintained the highest redox potential. Accordingly, the synergistic effect of photocatalysis and PMS activation enhanced cipro degradation. Free radical and non-radical species including , h+, 1O2, •OH and co-existed in the coupled system. Impressively, this study provides a handy approach for oxygen vacancy regulation in metallic oxides composite and an easily recycled catalyst with high-activity in coupled oxidation system towards antibiotic degradation.

Product line transformation, foreign sales, and firm value: Evidence from COVID-19 pandemic governance in urban China.

Using a sample of Chinese firms, we examine stock market reaction to firms that announce a change in their product lines to those related to COVID-19 management (medical masks and ventilators, among others). We find the market reacts positively to the announcements. In addition, when a firm ordinarily has a large share of export sales, the stock market reaction is more salient, indicating that export sales provide a certification effect that positively signals investors. Additional analysis on moderating effects suggest that, conditional on foreign sales, prior experience with medical product lines or less uncertainty about supply availability enhances the cumulative announcement returns (CARs), while the adverse impact of firm size on CAR magnifies.

Anticancer effects of ovatodiolide on human prostate cancer cells involves cell cycle arrest, apoptosis and blocking of Ras/Raf/MEK/ERK signaling pathway.

PURPOSE: The current research was set with a goal to characterize the anticancer role of ovatodiolide against human prostate cancer along with the underlying mechanism of its action. METHODS: The proliferation of prostate cancer cells was assessed by using the CCK8 reagent. DAPI and acridine orange (AO)/ ethidium bromide (EB) staining procedures were employed for the analysis of cell apoptosis. Flow cytometric examination of prostate cancer cells was undertaken for the mitotic cell cycle analysis. The western blotting technique was used for the inference of expression levels of the proteins of interest. RESULTS: In vitro administration of ovatodiolide led to decline of proliferation of prostate cancer cells. The reduction in proliferative rates was attributed to the induction of apoptosis of prostate cancer cells and mitotic cell cycle arrest. Furthermore, the anticancer effects of ovatodiolide on prostate cancer cells were exerted through the inhibition of Ras/Raf/MEK/ERK signaling cascade. CONCLUSION: This study established the anticancer role of diterpenoid ovatodiolide in restricting the growth and proliferation of human prostate cancer cells.

An activity-based fluorescent probe and its application for differentiating alkaline phosphatase activity in different cell lines.

Herein, a new fluorescent probe, AE-Phos, is reported for detecting the ALP activity with the combined advantages of aggregation-induced emission (AIE) and excited state intramolecular proton transfer (ESIPT). Further detailed fluorescence experiments demonstrated that AE-Phos exhibited excellent selectivity and sensitivity, a large Stokes shift, and a fast response towards ALP. Furthermore, AE-Phos was applied to imaging the ALP activity in different cell lines quantitatively.

Clinical Application of Contrast-Enhanced Ultrasound Using High-Frequency Linear Probe in the Detection of Small Colorectal Liver Metastases.

To compare the performance of contrast-enhanced ultrasound (CEUS) using high-frequency linear and convex probes in the detection of small colorectal liver metastases (CRLMs). A total of 85 patients with 143 small CRLMs were evaluated. High-frequency ultrasound (US) and CEUS detected significantly more superficial lesions within 60 mm below the skin than a convex probe (p <0.05). The detection rate decreased in the chemotherapy group, especially when using a convex probe for US (p <0.05). By combining convex and linear probes, detection rates of US and CEUS were significantly higher than that of a convex or a linear probe alone (p <0.05). High-frequency US and CEUS helped to improve detection of small CRLMs and reduce the influence of chemotherapy. For patients with a high risk of CRLMs and those after chemotherapy, we recommend first scanning the liver by using a convex probe and subsequently screening the surface area of the liver and suspicious small lesions by using a linear probe.

Preliminary Analysis of Clinical Situations Involved in Quantification of Contrast-Enhanced Ultrasound in Crohn's Disease.

To assess influencing factors for quantitative analysis of contrast-enhanced ultrasound (CEUS) in Crohn's disease (CD), dynamic CEUS examinations from 77 consecutive CD patients were recorded. Peak intensity (PI) values were calculated using the pre-installed quantification software of the ultrasound scanner. The influence of depth, pressure from the ultrasound probe and intraluminal gas was analyzed. The PI value of the anterior wall was lower than that of the posterior wall when the depth was ≤3.4 cm (17.9 dB vs. 21.3 dB; p < 0.05) or evident pressure was exerted (19.1 dB vs. 22.5 dB; p < 0.01). In the presence of intraluminal gas, the PI of the anterior wall was higher than that of the posterior wall (20.7 dB vs. 18.8 dB; p < 0.05). Nevertheless, no significant difference was found between the PI value of anterior and posterior walls when the depth was >3.4 cm (19.8 dB vs. 20.3 dB), moderate pressure was exerted (20.5 dB vs. 21.1 dB) or luminal gas was excluded between the two bowel walls (18.9 dB vs. 21.2 dB; p ≥ 0.05). The factors of depth, pressure from the ultrasound probe and intraluminal gas can affect the quantification results of CEUS. It is preferable to place the region of interest in the posterior wall when luminal gas is absent and in the anterior wall when luminal gas is present. In the latter case, more attention should be paid to reducing pressure by the ultrasound probe.

Breaking tolerance to self, circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell-depleted allogeneic hematopoietic cell transplantation.

Alloreactive natural killer (NK) cells are an important influence on hematopoietic stem cell transplantation (HSCT) outcome. In HLA-mismatched HSCT, alloreactivity occurs when licensed donor NK cells expressing inhibitory killer Ig-like receptors (KIR) for donor MHC class I ligands recognize the lack of the class I ligands in the mismatched recipient ("missing self"). Studies in HLA-matched HSCT, however, have also demonstrated improved outcome in patients lacking class I ligands for donor inhibitory KIR ("missing ligand"), indicating that classically nonlicensed donor NK cells expressing KIR for non-self MHC class I ligands may exhibit functional competence in HSCT. We examined NK function in 16 recipients of T cell-depleted allografts from HLA-identical or KIR-ligand matched donors after myeloablative therapy. After HSCT, nonlicensed NK cells expressing inhibitory KIR for non-self class I exhibit robust intracellular IFN-gamma and cytotoxic response to target cells lacking cognate ligand, gradually becoming tolerized to self by day 100. These findings could not be correlated with cytokine environment or phenotypic markers of NK development, nor could they be attributed to non-KIR receptors such as CD94/NKG2A. These findings confirm that NK alloreactivity can occur in HLA-matched HSCT, where tolerance to self is either acquired by the stem cell-derived NK cell after exiting the bone marrow or where tolerance to self can be temporarily overcome.

Chemical conjugation of muramyl dipeptide and paclitaxel to explore the combination of immunotherapy and chemotherapy for cancer.

Paclitaxel (Taxol) conjugated to muramyl dipeptide (MDP) is described. Biological testing showed that the conjugation of MDP at 2'-O-paclitaxel (2'- O -MTC-01) not only has antitumor activity, but also have immunoenhancement capacity. Compared with paclitaxel or MDP alone or with a mixture of paclitaxel + MDP, 2'- O -MTC-01 significantly increases the production and expression of TNF-alpha and IL-12 from mouse peritoneal macrophages, which demonstrates a synergism of MDP and paclitaxel in one conjugated molecule.

Hierarchy of the human natural killer cell response is determined by class and quantity of inhibitory receptors for self-HLA-B and HLA-C ligands.

The interaction of NK inhibitory killer Ig-like receptors (KIRs) with self-MHC class I molecules mediates NK tolerance to self while conferring functional competence. Through single-cell analysis of intracellular IFN-gamma production and NK clone cytotoxicity we evaluated the resting NK repertoire, analyzing the responsiveness of NK subgroups expressing discrete combinations of non-KIR and KIR class I-specific receptors. CD94:NKG2A and Ig-like transcript 2 (ILT2)-expressing cells have a modest response to class I-negative target cells, but NK cells expressing inhibitory KIRs to self-MHC class I ligands, both HLA-B and HLA-C ligands, achieve significantly higher effector capacity. There is a dose effect of KIR for self-MHC on effector capacity, but even in the most highly responsive NK cells expressing more than one inhibitory KIR for self-MHC the presentation of only one cognate MHC ligand is sufficient to abolish response. Among KIR(+) cells there is preferential expression for inhibitory KIR for self-MHC. The likelihood of KIR expression is influenced by whether other KIRs are already expressed on the same cell, supporting a model of serial acquisition of KIR expression. These findings define how inhibitory receptor and autologous HLA interactions impact single-cell function and demonstrate that the resting human NK repertoire is highly attuned but variegated in response. These findings have important implications for the resting NK response to viral pathogens and malignancy, for donor selection in allogeneic hemopoietic cell transplantation, and for models of NK tolerance.

Ginsenoside-Ro enhances cell proliferation and modulates Th1/Th2 cytokines production in murine splenocytes.

AIM: To study the effects of ginsenoside-Ro on cell proliferation and cytokine production in murine splenocytes. METHODS: The effect of ginsenoside-Ro on murine splenocytes proliferation was studied using [3H] thymidine incorporation assay. Effects of ginsenoside-Ro on the production of cytokines interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) from murine splenocytes were detected by ELISA method. Effects of ginsenoside-Ro on mRNA level of Th1 cytokine IFN-gamma and Th2 cytokine IL-4 were evaluated by reverse transcription polymerase chain reaction (RT-PCR) analysis. RESULTS: Ginsenoside-Ro showed no mitogenic effect on unstimulated murine splenocytes. It enhanced the proliferation of Con A-induced murine splenocytes and the production of IL-2 at concentrations of 1-10 micromol x L(-1). Moreover, ginsenoside-Ro increased the production and expression of Th2 cytokine IL-4 and decreased the production and expression of Th1 cytokine IFN-gamma in Con A-induced murine splenocytes at concentrations of 2-10 micromol x L(-1). CONCLUSION: Ginsenoside-Ro showed immunomodulatory effects by regulating the production and expression of Th1/Th2 cytokines in murine splenocytes.

Protopanaxatriol-type ginsenosides differentially modulate type 1 and type 2 cytokines production from murine splenocytes.

Seven protopanaxatriol-type ginsenosides and their aglycones including PPT, PT, -Re, -Rg (1), -F (1), -Rh (1), 20(R)-Rh (1) which are closely related in structure were studied for their effects on type 1 and type 2 cytokines production from murine splenocytes and their related mechanisms were examined. The results indicate that PPT, PT and ginsenoside-Re show hardly any or weak effects on concanavalin A (Con A)-induced production of IFN-gamma and IL-4. Ginsenoside-Rh (1) and 20(R)-Rh (1) induce a Con A-induced type 1 cytokine pattern by increasing the production of interleukin-12 (IL-12), the expression of IFN-gamma, T-bet and enhancing NF-kappaB DNA binding activity. In contrast ginsenosides-Rg (1) and -F (1) cause a Con A-induced type 2 cytokines response by increasing the expression of IL-4, GATA-3 and enhancing NF-kappaB DNA binding activity. Thus, these protopanaxatriol-type ginsenosides have different immunomodulatory effects, which might explain the complex immunomodulatory effect of Panax ginseng.

Immunoenhancing activity of protopanaxatriol-type ginsenoside-F3 in murine spleen cells.

AIM: To investigate the immunoenhancing activity of ginsenoside-F3 in murine spleen cells and explore its mechanism. METHODS: The enhancing effect of ginsenoside-F3 on murine spleen cell proliferation was studied using [3H]thymidine incorporation assay. Effects of ginsenoside-F3 on the production of type 1 cytokines IL-2, IFN-gamma, and type 2 cytokines IL-4 and IL-10 from murine spleen cells were detected by ELISA method. Effects of ginsenoside-F3 on mRNA level of cytokines IL-4, IFN-gamma, and transcription factors T-bet and GATA-3 were evaluated by RT-PCR analysis. Effect of ginsenoside-F3 on NF-kappaB DNA binding activity in murine spleen cells was investigated by electrophoretic mobility shift assays (EMSA). RESULTS: Ginsenoside-F3 at 0.1-100 micromol/L not only promoted the murine spleen cell proliferation, but also increased the production of IL-2 and IFN-gamma, while decreased the production of IL-4 and IL-10 from murine spleen cells with the maximal effect at 10 micromol/L. RT-PCR analysis displayed that ginsenoside-F3 enhanced the IFN-gamma and T-bet gene expression and decreased IL-4 and GATA-3 gene expression. EMSA experiment showed that ginsenoside-F3 10 micromol/L enhanced the NF-kappaB DNA binding activity induced by ConA in murine spleen cells. CONCLUSION: Ginsenoside-F3 has immunoenhancing activity by regulating production and gene expression of type 1 cytokines and type 2 cytokines in murine spleen cells.

Parallel approach for solution-phase synthesis of 2-quinoxalinol analogues and their inhibition of LPS-induced TNF-alpha release on mouse macrophages in vitro.

A parallel solution-phase synthesis of 2-quinoxalinol analogues is described. The key step-simultaneous reductions of m-Ar(NO2)2 to m-Ar(NH2)2 was investigated extensively. We obtained preliminary pharmacological activity of those analogues for the inhibition of LPS-induced TNF-alpha release on mouse macrophage in vitro. Two compounds revealed inhibitory activity, with IC50 values of 0.40 microM (7-amino-6-[(3-methoxypropyl)amino]-3-methyl-2-quinoxalinol) and 2.2 microM (7-amino-6-[(3-butoxypropyl)amino]-3-methyl-2-quinoxalinol), respectively.