Wnt10b protects cardiomyocytes against doxorubicin-induced cell death via MAPK modulation.

BACKGROUND: Doxorubicin, an anthracycline chemotherapeutic known to incur heart damage, decreases heart function in up to 11% of patients. Recent investigations have implicated the Wnt signaling cascade as a key modulator of cardiac tissue repair after myocardial infarction. Wnt upregulation in murine models resulted in stimulation of angiogenesis and suppression of fibrosis after ischemic insult. However, the molecular mechanisms of Wnt in mitigating doxorubicin-induced cardiac insult require further investigation. Identifying cardioprotective mechanisms of Wnt is imperative to reducing debilitating cardiovascular adverse events in oncologic patients undergoing treatment. METHODS: Exposing human cardiomyocyte AC16 cells to varying concentrations of Wnt10b and DOX, we observed key metrics of cell viability. To assess the viability and apoptotic rates, we utilized MTT and TUNEL assays. We quantified cell and mitochondrial membrane stability via LDH release and JC-1 staining. To investigate how Wnt10b mitigates doxorubicin-induced apoptosis, we introduced pharmacologic inhibitors of key enzymes involved in apoptosis: FR180204 and SB203580, ERK1/2 and p38 inhibitors. Further, we quantified apoptotic executor enzymes, caspase 3/7, via immunofluorescence. RESULTS: AC16 cells exposed solely to doxorubicin were shrunken with distorted morphology. Cardioprotective effects of Wnt10b were demonstrated via a reduction in apoptosis, from 70.1% to 50.1%. LDH release was also reduced between doxorubicin and combination groups from 2.27-fold to 1.56-fold relative to the healthy AC16 control group. Mitochondrial membrane stability was increased from 0.67-fold in the doxorubicin group to 5.73 in co-treated groups relative to control. Apoptotic protein expression was stifled by Wnt10b, with caspase3/7 expression reduced from 2.4- to 1.3-fold, and both a 20% decrease in p38 and 40% increase in ERK1/2 activity. CONCLUSION: Our data with the AC16 cell model demonstrates that Wnt10b provides defense mechanisms against doxorubicin-induced cardiotoxicity and apoptosis. Further, we explain a mechanism of this beneficial effect involving the mitochondria through simultaneous suppression of pro-apoptotic p38 and anti-apoptotic ERK1/2 activities.

Extraordinary Titer and Broad Anti-SARS-CoV-2 Neutralization Induced by Stabilized RBD Nanoparticles from Strain BA.5.

The receptor-binding domain (RBD) of the SARS-CoV-2 spike is a primary target of neutralizing antibodies and a key component of licensed vaccines. Substantial mutations in RBD, however, enable current variants to escape immunogenicity generated by vaccination with the ancestral (WA1) strain. Here, we produce and assess self-assembling nanoparticles displaying RBDs from WA1 and BA.5 strains by using the SpyTag:SpyCatcher system for coupling. We observed both WA1- and BA.5-RBD nanoparticles to degrade substantially after a few days at 37 °C. Incorporation of nine RBD-stabilizing mutations, however, increased yield ~five-fold and stability such that more than 50% of either the WA1- or BA.5-RBD nanoparticle was retained after one week at 37 °C. Murine immunizations revealed that the stabilized RBD-nanoparticles induced ~100-fold higher autologous neutralization titers than the prefusion-stabilized (S2P) spike at a 2 µg dose. Even at a 25-fold lower dose where S2P-induced neutralization titers were below the detection limit, the stabilized BA.5-RBD nanoparticle induced homologous titers of 12,795 ID50 and heterologous titers against WA1 of 1767 ID50. Assessment against a panel of ß-coronavirus variants revealed both the stabilized BA.5-RBD nanoparticle and the stabilized WA1-BA.5-(mosaic)-RBD nanoparticle to elicit much higher neutralization breadth than the stabilized WA1-RBD nanoparticle. The extraordinary titer and high neutralization breadth elicited by stabilized RBD nanoparticles from strain BA.5 make them strong candidates for next-generation COVID-19 vaccines.

A Novel Identified Long Intergenic Noncoding RNA, LINC01574, Contributes to Breast Cancer Deterioration via the Regulation of miR-6745/TTYH3 Axis.

Objective: Compelling evidence suggested that lncRNAs performed vital functions in the development of breast cancer (BC). The study intended to mine the functional roles of LINC01574 in BC and further excavated its underlying regulatory mechanism. Methods: The expression and prognosis of LINC01574 in BC were detected by integrating analysis of data mining, bioinformatics, and RT-qPCR. Then, the effect of LINC01574 knockdown on BC cell growth and metastasis was evaluated in vitro and in vivo. Interactions between miR-6745 and LINC01574 or TTYH3 were revealed by both target prediction and dual luciferase reporter assay. Results: Our data found that LINC01574 was markedly elevated in BC tissues and cells and was an independent prognostic risk factor for patients with BC. Further functional studies revealed that knockdown of LINC01574 remarkably inhibited the growth and metastasis of BC cells in vitro and in vivo. Mechanistically, LINC01574 competitively binds with miR-6745 to prevent the degradation of TTYH3, thereby promoting the development of BC. Conclusion: Our results unmasked a novel LINC01574/miR-6745/TTYH3 regulatory axis in BC progression and suggested that LINC01574 might be a promising prognostic indicator and therapeutic target for patients with BC.

Gastrointestinal metastatic signet ring cell breast cancer in young females: a case report.

Background: Signet ring cell carcinoma (SRCC) is characterized by strong invasiveness and rapid progression. It occurs mostly in young and middle-aged patients, and early patients may have no clinical symptoms. Gastric SRCC with breast cancer metastasis is relatively rare. It often presents challenges for clinicians and pathologists and may lead to an absolutely different therapeutic strategy. Case Description: In this paper, we report on a 37-year-old woman who was admitted to the hospital with a left breast mass discovered 5 days earlier, the mass was occasionally painful, and there was no skin swelling, skin depression, or other abnormalities. The initial diagnosis considered her to have a left breast tumor. The patient was previously healthy with no family history of tumor. Considering the possibility of malignant lesions, she underwent resection of the left breast tumor and surrounding tissue. Postoperative pathological findings suggested SRCC (left breast mass). Although the patient had no history of gastrointestinal tumors, considering that SRCC can also appear in the gastrointestinal tract and other organs. We performed gastroscopy on the patient, showed an ulcerative mass in the greater curvature of the gastric body, with irregular nodular uplift of the surrounding mucosa. The excised breast lesions were analyzed by immunohistochemistry, and the pathological result showed SRCC (left breast tumor). Combined with the results of immunohistochemistry, it was consistent with gastrointestinal metastasis. Through our multi-faceted differential diagnosis, the final diagnosis of the patient was clear, which not only bought time for the patient's subsequent treatment, but also avoided misdiagnosis and blind treatment due to the particularity and rarity of the case. Conclusions: Gastric cancer should be considered when breast tumors show SRCC without in situ lesion. Signet ring cell gastric cancer (occult) should be excluded even if the patient has no family history of gastric cancer. It is important to distinguish metastatic cancer from primary breast cancer to avoid misdiagnosis and blind treatment due to the particularity of the case, at which point an early recognition can be made and an optimal treatment plan can be chosen.

Mechanism of Photocurrent Degradation and Contactless Healing in p-Type Mg-Doped Gallium Nitride Thin Films.

Light-induced degradation (LID) phenomenon is commonly found in optoelectronics devices. Self-healing effect in halide lead perovskite solar cells was investigated since the electrons and holes in the shallow traps could escape easily at room temperature. However, the degradation in the semiconductors could not easily recover at room temperature, and many of them needed annealing at temperatures in the several hundreds, which was not friendly to the integrated optoelectronic semiconductor devices. To solve this problem, in this work, LID effect of photocurrent in p-type Mg-doped gallium nitride thin films was investigated, and deep defect and vacancy traps played a vital role in the LID and healing process. This work provides a contactless way to heal the photocurrent behavior to its initial level, which is desirable in integrated devices.

Enhanced electron transportation of PF-NR2 cathode interface by gold nanoparticles.

In order to achieve a wider organic light-emitting diode (OLED) commercial popularity, solution processing inverted polymer light-emitting diode (iPLED) is a trend for further development, but there is still a gap for solution processing devices to achieve commercialization. The improvement of the performance iPLEDs is a research topic of intense current interest. The modification of the cathode interface layer of poly[(9,9-bis(3'-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)] (PF-NR2) can greatly improve the performance of the devices. However, the electron transportation of the cathode interface layer of PF-NR2 films is currently poor, and there is substantial interest in improving its electron transportation to further enhance the performance of organic optoelectronic devices. In this paper, gold nanoparticles (Au NPs) with a particle size of 20 nm were prepared and doped into the interface layer PF-NR2 at a specified ratio. The electron transportation of the interface layer of PF-NR2 was greatly improved, as judged by conductive atomic force microscopy measurements, which is due to the excellent conductivity of Au NPs. Herein, we demonstrate improved electron transportation of the interface layer by doping Au NPs in PF-NR2 film, which provides important and practical theoretical guidance and technical support for the preparation of high performance organic optoelectronic devices.

Two-dimensional shape retrieval from the interferometric out-of-focus image of a nonspherical particle-Part I: theory.

Shape is one of the important characteristics of nonspherical particles. Herein, the two-dimensional shapes of several micrometer/millimeter-sized particles with a variety of geometrical forms are retrieved from simulated interferometric out-of-focus images using the Hybrid Input-Output algorithm. The particle concerned can be either a single particle or a complex particle with separate parts. The impact of the axial size of the three-dimensional particle on the retrieval of the two-dimensional shape (i.e., the projection of the particle on the image sensor) is analyzed, showing that an increase of the axial size increases the deviation of low frequencies in the interferometric out-of-focus image and eventually degrades the quality of the reconstructed shape. This study demonstrates the capability of the interferometric out-of-focus imaging technique on shape information retrieval for micrometer/millimeter-sized nonspherical particles.

Synthesis and photoluminescent properties of NaYF4:Eu3+ core and NaYF4:Eu3+/NaYF4 core/shell nanocrystals.

NaYF4:Eu3+ core and NaYF4:Eu3+/NaYF4 core/shell nanocrystals (NCs) were synthesized via a wet chemical method. The transmission electron microscope photographs show that the core and core/shell nanoparticles are monodisperse and uniform NCs with average diameters of 22 and 26 nm respectively. The photoluminescence (PL) properties of the samples, including the PL excitation and emission spectra, and luminescent decay curves, are investigated in detail. The results show that the intensity of 5D2 emission relative to that of 5D0 is stronger in NaYF4:Eu3+/NaYF4 core/shell NCs than that in NaYF4:Eu3+ core NCs, and a longer decay lifetime of 5D2 is observed in core/shell samples. In addition, from the corrected emission spectra of 5D0, the 5D0 radiative lifetimes were calculated. These together with the measured decay lifetime of 5D0 emission give the intrinsic quantum yields of 5D0. The results were well interpreted by considering the surface effects.

[Investigation on the infection of Blastocystis hominis in populations in Bama Yao Autonomous County of Guangxi].

497 fecal specimens were collected from 5 randomly selected villages of Bama County in December 2011, and tested for Blastocystis hominis infection using improved centrifugal sedimentation with hydrochloric acid-ether. Data were analyzed by villages, gender, occupation, age groups and ethnic populations. The results showed that 215 people of 497 were positive, with a prevalence of 43.3% (215/497). Pandang village had the highest infection rate of 55.7% (68/122), significantly higher than the other villages (P<0.05). There was no significant difference in genders, occupations, age groups and ethnic populations (P>0.05).

[Expressions and significance of IL-17 and IL-23 in intestinal mucosa of mice infected with Blastocystis hominis].

OBJECTIVE: To study the expressions of interleukin-17 (IL-17) and interleukin-23 (IL-23) in the intestinal mucosa of BABL/C mice infected with Blastocystis hominis. METHODS: A total of 30 BABL/C mice were randomly divided into different groups: an experimental group, an immunosuppressant group and a normal group. Each mouse of the experimental group and immunosuppressant group was administered intraperieneally with dexamethasone (2 mg, gd, for 5 days) and one of the control group was given physiological saline (0.2 ml). In the experimental group, each mouse was infected with Blastocystis hominis (107 parasites per 0.5 ml) by the intragastric infusion method; in the immunosuppressant group and normal group, the mice were fed with equal physiological saline. On the fifth day post-infection, the duodenum, jejunum, ileum and colon of the mice of the 3 groups were taken out for the tissue section. The pathological changes of bowel mucosa were determined by HE staining, and the expressions of IL-17 and IL-23 in different parts of bowel mucosa were determined by immunohistochemistry assay. RESULTS: The pathological examinations showed intestinal mucosa had various degrees of inflammatory changes. The expressions of IL-17 and IL-23 in the intestinal mucosa of the mice in the experimental group was significantly higher than those in the immunosuppressant group or normal group (both P < 0.05). The expressions of IL-17 and IL-23 in the intestinal mucosa of the mice in the immunosuppressant group were similar to those in the normal group (P > 0.05). The expression of IL-17 in the duodenum or jejunum or colon of the mice was significantly higher than that in the ileum in the experimental group (P < 0.05). The expression of IL-23 in the duodenum or jejunum of the mice was significantly higher that that in the ileum or colon in the experimental group (P < 0.05). CONCLUSIONS: IL-17 and IL-23 are highly expressed in the intestinal mucosa of the mice infected with Blastocystis hominis. IL-23 may also be involved in the immunomodulatory effects of Blastocystis hominis infection, which plays a mutual regulatory role with IL-17.

Synthesis and luminescent properties of LuAG : Ce3+ transparent ceramics by solvo-thermal method.

The precursor powders of LuAG : Ce3+ transparent ceramics were synthesized by solvo-thermal method. The crystal structure and morphology of powders were analyzed by means of Fourier transform infra-red spectroscopy, X-ray diffraction and scanning electron microscopy. The precursor powders were sintered into transparent ceramics in vacuum and then in nitrogen without any additive. The surface morphology of the transparent unpolished ceramics was characterized using scanning electron microscopy. Some factors that affect the transparency of ceramics were discussed. The UV-Vis fluorescence excitation and emission spectra of LuAG : Ce3+ transparent ceramics were measured. The vacuum ultraviolet spectra of transparent ceramics were investigated using the synchrotron radiation as the excitation source. The excitation mechanism of Ce3+ was discussed at different excitation wavelength.