Silica-supported dichlorophosphate: a recoverable cyclodehydrant for the eco-friendly synthesis of 2,5-disubstituted 1,3,4-oxadiazoles under solvent-free and microwave irradiation conditions

A series of symmetrical and unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles were efficiently synthesized from the cyclodehydration of diacylhydrazines by using silica-supported dichlorophosphate as a recoverable cyclodehydrant in solvent-free medium under microwave irradiation. This protocol has advantages of no corrosion, no environmental pollution, accelerated rate, high yield and simple work-up procedure

Malignant melanoma of the penis and urethra: one case report

We present a case of a patient with malignant melanoma of the glans penis and urethra, which was found in a 53-year-old man with nonhealing ulcerative penile lesion and bilateral, clinically palpable inguinal lymphadenopathies at diagnosis. A diagnostic biopsy showed the characteristics of a melanoma. We treated the patient with total penectomy and bilateral inguinal lymph node dissection. After surgery, chemotherapy with bleomycin, vincristine and cisplatin and immunotherapy with thymosin injection were started. No recurrence or metastasis occurred during the 3 years after the operation. Melanoma of the penis is very rare, and early diagnosis is important because the patient prognosis is very poor

Assessment of left ventricular function in patients with type 2 diabetes mellitus by non-invasive myocardial work

BackgroundDiabetes mellitus (DM) is a chronic disease that poses a serious risk of cardiovascular diseases. Therefore, early detection of impaired cardiac function with non-invasive myocardial imaging is critical for improving the prognosis of patients with DM.PurposeThis study aimed to assess the left ventricular (LV) function in patients with type 2 diabetes mellitus (T2DM) by non-invasive myocardial work technique.Materials and methodsIn all, 67 patients with T2DM and 28 healthy controls were included and divided into a DM group and a control group. Two-dimensional dynamic images of apical three-chamber view, apical two-chamber view, and apical four-chamber view were collected from all subjects, consisting of at least three cardiac cycles. LV myocardial strain parameters, including global longitudinal strain (GLS) and peak strain dispersion (PSD), as well as myocardial work parameters, including global constructive work (GCW), global wasted work (GWW), global work index (GWI), and global work efficiency (GWE), were obtained and analyzed.ResultsA total of 15 subjects were randomly selected to assess intra-observer and inter-observer consistency of myocardial work parameters and strain parameters, which showed excellent results (intra-class correlation coefficients: 0.856 - 0.983, P<0.001). Compared with the control group, the DM group showed significantly higher PSD (37.59 ± 17.18 ms vs. 27.72 ± 13.52 ms, P<0.05) and GWW (63.98 ± 43.63 mmHg% vs. 39.28 ± 25.67 mmHg%, P<0.05), and lower GWE (96.38 ± 2.02% vs. 97.72 ± 0.98%, P<0.001). Furthermore, the PSD was positively correlated with GWW (r = 0.565, P<0.001) and negatively correlated with GWE (r = -0.569, P<0.001).ConclusionUncoordinated LV myocardial strain, higher GWW, and lower GWE in patients with T2DM may serve as indicators for the early assessment of cardiac impairment in T2DM

Upconversion NIR-II fluorophores for mitochondria-targeted cancer imaging and photothermal therapy

Acknowledgements: The work was supported by the National Key R&D Program of China (2020YFA0908800), NSFC (81773674, 81573383), Shenzhen Science and Technology Research Grant (JCYJ20190808152019182), Hubei Province Scientific and Technical Innovation Key Project, National Natural Science Foundation of Hubei Province (2017CFA024, 2017CFB711), the Applied Basic Research Program of Wuhan Municipal Bureau of Science and Technology (2019020701011429), Tibet Autonomous Region Science and Technology Plan Project Key Project (XZ201901-GB-11), the Local Development Funds of Science and Technology Department of Tibet (XZ202001YD0028C), Project First-Class Disciplines Development Supported by Chengdu University of Traditional Chinese Medicine (CZYJC1903), Health Commission of Hubei Province Scientific Research Project (WJ2019M177, WJ2019M178), the China Scholarship Council, and the Fundamental Research Funds for the Central Universities.Peer reviewedPublisher PD

The impact of stereotype threat on endogenous poverty-elimination dynamics in generationally poor individuals

IntroductionThe study examines the impact of stereotype threat on generationally poor individuals and its effect on achievement motivation. It also explores the extent to which self-affirmation has an intervention effect on the negative impact of stereotype threat.Methods and resultsIn Study 1, statements that contained negative stereotypes were used to elicit stereotype threat in generationally poor individuals; the results show that stereotype threat reduced the performance of generationally poor individuals in a mental-rotation task. Study 2 used a questionnaire to measure the endogenous dynamics of generationally poor individuals attempting to escape poverty after experiencing stereotype threat; participants in the stereotype-threat group showed lower-level endogenous poverty-elimination dynamics than those in the control group. In Study 3, a self-affirmation intervention was administered to the stereotype-threat group after the stereotype threat was induced. Participants in the self-affirmation group were shown to have higher-level endogenous poverty-elimination dynamics than those in the control group.DiscussionThese findings confirm the negative effect of stereotype threat on endogenous poverty-elimination dynamics and verify the effectiveness of self-affirmation in mitigating the negative effects of stereotype threat

Identification of potential biomarkers and pathways for asthenozoospermia by bioinformatics analysis and experiments

BackgroundAsthenozoospermia, a type of male infertility, is primarily caused by dysfunctional sperm mitochondria. Despite previous bioinformatics analysis identifying potential key lncRNAs, miRNAs, hub genes, and pathways associated with asthenospermia, there is still a need to explore additional molecular mechanisms and potential biomarkers for this condition.MethodsWe integrated data from Gene Expression Omnibus (GEO) (GSE22331, GSE34514, and GSE160749) and performed bioinformatics analysis to identify differentially expressed genes (DEGs) between normozoospermia and asthenozoospermia. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to gain insights into biological processes and signaling pathways. Weighted Gene Co-expression Network Analysis (WGCNA) identified gene modules associated with asthenozoospermia. Expression levels of key genes were assessed using datasets and experimental data. Gene Set Enrichment Analysis (GSEA) and correlation analysis identified pathways associated with the hub gene and explore the relationship between the ZNF764 and COQ9 and mitochondrial autophagy-related genes. Competitive endogenous RNA (ceRNA) networks were constructed, and in vitro experiments using exosome samples were conducted to validate this finding.ResultsCOQ9 was identified as a marker gene in asthenozoospermia, involved in autophagy, ATP-dependent chromatin remodeling, endocytosis, and cell cycle, etc. The ceRNA regulatory network (LINC00893/miR-125a-5p/COQ9) was constructed, and PCR demonstrated that LINC00893 and COQ9 were downregulated in asthenozoospermia, while miR-125a-5p and m6A methylation level of LINC00893 were upregulated in asthenozoospermia compared to normozoospermic individuals.ConclusionThe ceRNA regulatory network (LINC00893/miR-125a-5p/COQ9) likely plays a crucial role in the mechanism of asthenozoospermia. However, further functional experiments are needed to fully understand its significance

Effects of physical crosslinking methods on digestibility in vitro and safety of edible packaging: A primary study on collagen films

Crosslinking is often used to improve the mechanical strength and barrier properties of edible films. However, the effects on films’ digestibility and edible safety are still unknown. Herein, four crosslinking methods were utilized to crosslink collagen films, including UV irradiation, dehydrothermal treatment (DHT), tannin and glutaraldehyde. The crosslinked samples were then researched via in vitro digestion and cell culture model. With the INFOGEST method, the results of dry matter loss, degree of hydrolysis and absorbed collagen content have significantly correlated relations and showed excellent digestive ability of UV treated and DHT films. The results of the FTIR suggest that the crosslinking affects the structure of digestion and absorption. The toxicity and nutrition of the hydrolytes of collagen films were measured in Caco-2 and HepG-2 cells, and the collagen films, especially UV treated and tannin treated films, can promote cell growth while the glutaraldehyde treated one reduced cell viability presumably due to its residual in the films

Targeting a thrombopoietin-independent strategy in the discovery of a novel inducer of megakaryocytopoiesis, DMAG, for the treatment of thrombocytopenia

Thrombocytopenia is a thrombopoietin (TPO)-related disorder with very limited treatment options, and can be lifethreatening. There are major problems with typical thrombopoietic agents targeting TPO signaling, so it is urgent to discover a novel TPO-independent mechanism involving thrombopoiesis and potential druggable targets. We developed a drug screening model by the multi-grained cascade forest (gcForest) algorithm and found that 3,8-di-O-methylellagic acid 2- O-glucoside (DMAG) (10, 20 and 40 μM) promoted megakaryocyte differentiation in vitro. Subsequent investigations revealed that DMAG (40 mM) activated ERK1/2, HIF-1b and NF-E2. Inhibition of ERK1/2 blocked megakaryocyte differentiation and attenuated the upregulation of HIF-1b and NF-E2 induced by DMAG. Megakaryocyte differentiation induced by DMAG was inhibited via knockdown of NF-E2. In vivo studies showed that DMAG (5 mg/kg) accelerated platelet recovery and megakaryocyte differentiation in mice with thrombocytopenia. The platelet count of the DMAG-treated group recovered to almost 72% and 96% of the count in the control group at day 10 and 14, respectively. The platelet counts in the DMAG-treated group were almost 1.5- and 1.3-fold higher compared with those of the irradiated group at day 10 and 14, respectively. Moreover, DMAG (10, 25 and 50 mM) stimulated thrombopoiesis in zebrafish. DMAG (5 mg/kg) could also increase platelet levels in c-MPL knockout (c-MPL-/-) mice. In summary, we established a drug screening model through gcForest and demonstrated that DMAG promotes megakaryocyte differentiation via the ERK/HIF1/NF-E2 pathway which, importantly, is independent of the classical TPO/c-MPL pathway. The present study may provide new insights into drug discovery for thrombopoiesis and TPO-independent regulation of thrombopoiesis, as well as a promising avenue for thrombocytopenia treatment

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO