miR-330-5p Suppress Cell Growth and Invasion via Disrupting HSF4-mediated MACC1/STAT3 Pathway in Colorectal Cancer.

BACKGROUND: Recently, miRNAs are demonstrated to restrain mRNA translation through novel pattern with bind complementary sites in the coding sequence (CDS). Heat Shock Transcription Factor 4 (HSF4) has been newly described as a tumor-associated transcription factor. Therefore, the present study intends to explore miRNAs that bind CDS region of HSF4, and identify the function of their interactions in the malignant biological behavior of colorectal cancer (CRC). METHODS: Prognostic value of HSF4 and correlation between HSF4 and MACC1 expression were estimated via bioinformatics with the Cancer Genome Atlas (TCGA) data. HSF4 and downstream MACC1/STAT3 signaling cascade was characterized by immunoblotting. To characterize the effects of miR-330-5p and HSF4 on the malignant phenotype of CRC cells by functional experiments. The binding activity of miR-330-5p to coding sequence (CDS) of HSF4 was identified using DIANA-microT-CDS algorithm and dual-luciferase reporter assay. RESULTS: HSF4 was aberrantly overexpressed and associated with poor outcomes of CRC patients. Overexpression of HSF4 was correlated with Tumor Node Metastasis stage, and positively regulated malignant behaviors such as growth, migration, invasion of CRC cells. Moreover, miR-330-5p suppressed CRC cell growth, colony formation, migration and invasive. Interestingly, miR-330-5p recognized complementary sites within the HSF4 CDS region to reduce HSF4 expression. In rescue experiments, restoration of HSF4 expression functionally alleviated miR-330-5p-induced inhibition of cell growth, colon formation, invasion, and wound healing of CRC cells. HSF4 was associated positively with the well-known oncogenic factor MACC1 in TCGA cohort CRC samples, and knockdown of HSF4 resulted in downregulation of MACC1. In mechanism, MACC1 was suppressed upon miR-330-5p-induced downregulation of HSF4, leading to inactivation of phosphorylation of downstream STAT3. CONCLUSION: miR-330-5p suppresses tumors by directly inhibiting HSF4 to negatively modify activity of MACC1/STAT3 pathway.

Quantum illumination based on cavity-optomagnonics system with Kerr nonlinearity.

Quantum illumination is a quantum optical sensing technique, which employs an entangled source to detect low-reflectivity object immersed in a bright thermal background. Hybrid cavity-optomagnonics system promises to work as quantum illumination because a yttrium iron garnet (YIG) sphere can couple to microwave field and optical field. In this paper, we propose a scheme to enhance the entanglement between the output fields of the microwave and optical cavities by considering the intrinsic Kerr nonlinearity of the YIG. We investigate the difference between intrinsic Kerr nonlinearity and optomagnonical parametric-type coupling on improving entanglement. Our result show that the large value optomagnonical parametric-type coupling does not mean the large entanglement, nevertheless, the large value of Kerr nonlinearity does monotonously improve the entanglement for our group of parameters. Consequently, under feasible parameters of current experiment, the signal-to-noise ratio and probability of detection error can be improved after considering the magnon Kerr nonlinearity.

High glucose induces tau hyperphosphorylation in hippocampal neurons via inhibition of ALKBH5-mediated Dgkh m6A demethylation: a potential mechanism for diabetic cognitive dysfunction.

Tau hyperphosphorylation in hippocampal neurons has an important pathogenetic role in the development of diabetic cognitive dysfunction. N6-methyladenosine (m6A) methylation is the most common modification of eukaryotic mRNA and is involved in regulating diverse biological processes. However, the role of m6A alteration in tau hyperphosphorylation of hippocampus neurons has not been reported. We found lower ALKBH5 expression in the hippocampus of diabetic rats and in HN-h cells with high-glucose intervention, accompanied by tau hyperphosphorylation. ALKBH5 overexpression significantly reversed tau hyperphosphorylation in high-glucose-stimulated HN-h cells. Furthermore, we found and confirmed by m6A-mRNA epitope transcriptome microarray and transcriptome RNA sequencing coupled with methylated RNA immunoprecipitation that ALKBH5 regulates the m6A modification of Dgkh mRNA. High glucose inhibited the demethylation modification of Dgkh by ALKBH5, resulting in decreases in Dgkh mRNA and protein levels. Overexpression of Dgkh reversed tau hyperphosphorylation in HN-h cells after high-glucose stimulation. Overexpression of Dgkh by adenovirus suspension injection into the bilateral hippocampus of diabetic rats significantly ameliorated tau hyperphosphorylation and diabetic cognitive dysfunction. In addition, ALKBH5 targeted Dgkh to activate PKC-α, leading to tau hyperphosphorylation under high-glucose conditions. The results of this study reveal that high glucose suppresses the demethylation modification of Dgkh by ALKBH5, which downregulates Dgkh and leads to tau hyperphosphorylation through activation of PKC-α in hippocampal neurons. These findings may indicate a new mechanism and a novel therapeutic target for diabetic cognitive dysfunction.

Cysteine-rich 61(CYR61) alleviates cyclophosphamide-induced proliferation inhibition in ovarian granulosa cells via suppressing NLRP3/caspase1-mediated pyroptosis.

BACKGROUND: We investigated the level of Cysteine-rich 61 (CYR61) in premature ovarian failure as well as its regulatory molecular mechanism in this study. METHODS AND RESULTS: Cyclophosphamide (CTX) was used to induce OGCs (rat ovarian granulosa cells) and rats to establish in vivo and in vitro premature ovarian failure models. H&E staining was used to detect the pathological changes of ovarian histopathology. Si-NLRP3 (NOD-like receptor thermal protein domain associated protein 3, NLRP3) and si-CYR61 were transfected into OGCs using lipofectamine 3000. RT-qPCR and western blot were used to detect the expressions of CYR61 in ovarian tissue and OGCs. It showed that the expression of CYR61 was significantly down-regulated in premature ovarian failure model. Cell viability was detected using a Cell Counting Kit-8 (CCK-8) kit. TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling) staining was used to detect the apoptosis. 5-Ethynyl-2'-deoxyuridine (EdU) and SA-ß-gal (senescence-associated ß-galactosidase) staining were used to assess the proliferation and senescence. The expression of CYR61 in OGCs and ovarian tissues were detected by immunofluorescence and immunohistochemical staining. Overexpression of CYR61 significantly promoted OGCs proliferation and inhibited pyroptosis and apoptosis. Western blot was used to detect the protein expressions of p53 and p21 in OGCs. Flow cytometry was used to detect the pyroptosis. CYR61 overexpression inhibited the expression of NLRP3 and caspase-1 in CTX-induced OGCs according to western blot results. Moreover, we found that CYR61 overexpression down-regulated the protein expressions of p53 and p21 in CTX-induced OGCs. CONCLUSION: CYR61 inhibited CTX-induced OGCs senescence, and the mechanism may be related to the regulation of caspase-1/NLRP3-induced pyroptosis.

Improving mechanical cooling by using magnetic thermal noise in a cavity-magnomechanical system.

The cavity-magnomechanical system is a significant platform for studying quantum information. In this paper, a scheme to realize the ground-state cooling of the mechanical phonon mode in a cavity-magnomechanical system is proposed. In the general cooling method, the system is usually driven by a strong pumping field, and the Hamiltonian of the system needs to be linearized. Different from this cooling method, in a cavity-magnomechanical tripartite interaction system, we consider the magnetic thermal noise as an incoherent drive to facilitate cooling, where the thermal magnon number can enhance the effective coupling between the photon and phonon modes. The mechanical mode can be cooled to its ground state when the magnon thermal number is increased.

Simulating topological phases with atom arrays in an optical waveguide.

In this paper, we employ the atomic arrays in one-dimensional optical waveguides to simulate topological phases, where the waveguide is modeled as a one-dimensional infinitely long coupled cavity array. Under the Markov approximation, the coherent and dissipative coupling between atoms is established by eliminating waveguide modes. When the detuning between atoms and cavity fields lies in the band gap, the dynamics of the system is completely dominated by the coherent interaction. Under this condition, we designed three atomic arrays with different geometries and show that the topologically trivial and non-trivial phases of atomic arrays can be simulated. Furthermore, by introducing periodic atomic driving, the topological phase transition can be induced by adjusting the driving parameters. Finally, we investigate the effect of next-nearest neighbor interactions on topological state transfer and find that the next-nearest neighbor interactions break the degenerated bandgap state and establish a topological state transfer channel.

Simultaneous ground-state cooling of identical mechanical oscillators by Lyapunov control.

The simultaneous cooling of multiple mechanical oscillators in the cavity optomechanical system has aroused people's attention and may be applicable in the quantum information process. In this paper, a scheme to realize the simultaneous ground-state cooling of two identical mechanical oscillators is proposed, where the frequency of one of the oscillators is designed according to Lyapunov control. By this method, the dark mode can effectively couple with the bright mode so that the two identical oscillators can be simultaneously cooled to their ground state. Extending this scheme into multiple identical mechanical oscillators, we show that simultaneous cooling can also be achieved.

Unidirectional amplification in optomechanical system coupling with a structured bath.

Nonreciprocity plays an indispensable role in quantum information transmission. We theoretically study the unidirectional amplification in the non-Markovian regime, in which a nanosphere surrounded by a structured bath is trapped in a single (dual)-mode cavity. The global mechanical response function of the nanosphere is markedly altered by the non-Markovian structured bath through shifting the effective frequency and magnifying the response function. Consequently, when there is a small difference in the transmission rate within the regime of Markovian, the unidirectional amplification is achieved in the super-Ohmic spectral environment. In the double-optomechanical coupling system, the phase difference between two optomechanical couplings can reverse the transmission direction. Meanwhile, the non-Markovian bath still can amplify the signal because of the XX-type coupling between nanosphere and its bath.

Melatonin Protects Against Cyclophosphamide-induced Premature Ovarian Failure in Rats.

This study was designed to understand the efficacy and molecular cues of melatonin in cyclophosphamide(CTX)-induced premature ovarian failure (POF) in rats. Female SD rats were used to evaluate the potential effects of melatonin on the ovarian hormonal status, follicular development, and granulosa cells in CTX-treated rats. Here, we found that pretreatment with melatonin before CTX administration preserved the normal sex hormone levels, improved follicular morphology, and granulosa cell proliferation, and reduced apoptosis, as compared to the CTX treatment alone. Additionally, melatonin also up-regulated CYR6 and CTGF at the mRNA and protein levels. A potential mechanism is that melatonin inhibits LATS1, Mps1-One binder (MOB1), and YAP phosphorylation, thereby activating the Hippo signal pathway to promote its downstream targets, CYR61 and CTGF. In conclusion, pretreatment with melatonin effectively protected the ovaries against CTX-induced damage by activating the Hippo pathway. This study lay the foundation for the clinical application of melatonin for cancer patients with CTX treatment.

An Intelligent Rice Yield Trait Evaluation System Based on Threshed Panicle Compensation.

High-throughput phenotyping of yield-related traits is meaningful and necessary for rice breeding and genetic study. The conventional method for rice yield-related trait evaluation faces the problems of rice threshing difficulties, measurement process complexity, and low efficiency. To solve these problems, a novel intelligent system, which includes an integrated threshing unit, grain conveyor-imaging units, threshed panicle conveyor-imaging unit, and specialized image analysis software has been proposed to achieve rice yield trait evaluation with high throughput and high accuracy. To improve the threshed panicle detection accuracy, the Region of Interest Align, Convolution Batch normalization activation with Leaky Relu module, Squeeze-and-Excitation unit, and optimal anchor size have been adopted to optimize the Faster-RCNN architecture, termed 'TPanicle-RCNN,' and the new model achieved F1 score 0.929 with an increase of 0.044, which was robust to indica and japonica varieties. Additionally, AI cloud computing was adopted, which dramatically reduced the system cost and improved flexibility. To evaluate the system accuracy and efficiency, 504 panicle samples were tested, and the total spikelet measurement error decreased from 11.44 to 2.99% with threshed panicle compensation. The average measuring efficiency was approximately 40 s per sample, which was approximately twenty times more efficient than manual measurement. In this study, an automatic and intelligent system for rice yield-related trait evaluation was developed, which would provide an efficient and reliable tool for rice breeding and genetic research.

Favorable Genotypes of Type III Interferon Confer Risk of Dyslipidemia in the Population With Obesity.

Background: Studies have indicated that the chronic state of inflammation caused by obesity leads to dyslipidemia. However, how the polymorphisms involved in these inflammatory pathways affect the lipid metabolism in people with obesity is poorly understood. We investigated the associations of inflammation-related gene polymorphisms with dyslipidemia in individuals with obesity living in China. Methods: This case-control study in a population with obesity involved 194 individuals with dyslipidemia and 103 individuals without dyslipidemia. Anthropometric indices of obesity, fasting plasma glucose, blood pressure, blood lipids, and C-reactive protein were evaluated. The genes we tested were IL6 (interleukin 6), IL6R (interleukin 6 receptor), FOXP3 (forkhead box P3), TLR2 (toll-like receptor 2), TLR4 (toll-like receptor 4), IFNL3 (interferon lambda 3, formerly known as IL28B), and IFNL4 (interferon lambda 4, formerly known as IL29). Polymorphisms were genotyped using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Results: There were significant differences in the allelic and genotype frequencies of IFNL3 (IL28B) rs12971396, rs8099917, rs11882871, rs12979860, rs4803217 between non-dyslipidemia and dyslipidemia groups in people with obesity. These single nucleotide polymorphisms (SNPs) of IFNL3 were highly linked (D' and r > 0.90), so the result of one SNP could represent the result of other SNPs. For IFNL3 rs12971396, people with the homozygous genotype (the major group) carried a higher risk of dyslipidemia than people with the heterozygous genotype (P < 0.001, OR = 4.46, 95%CI, 1.95-10.22). Conclusions: The favorable genotypes of type III interferon, which have a beneficial role in anti-virus function, were associated with dyslipidemia in a Chinese population with obesity. Type III interferon could have a pathologic role and confer risk of dyslipidemia in people with obesity and chronic inflammation.

Nonlinearity enhancement and photon blockade in hybrid optomechanical systems.

The nonlinear optomechanical coupling is an attracting characteristic in the field of optomechanics. However, the strength of single photon optomechanical coupling is still within weak coupling regime. Using the optomechanical coupling to achieve strong nonlinear interaction between photons is still a challenge. In this paper, we propose a scheme by employing optomechanical and spin-mechanical interactions to enhance the nonlinearity of photons. An effective Hamiltonian is derived, which shows that the self-Kerr and cross-Kerr nonlinearity strengths can be enhanced by adjusting the classical pumping or enhancing the spin-mechanical coupling strength. In addition, we investigate the potential usage of the nonlinearity in the photon blockade. We demonstrate that the single and two photon blockades can occur in two super modes.

Photon blockade by enhancing coupling via a nonlinear medium.

A significantly low value of the single-photon coupling constant is a major challenge in the creation of a single-photon source via photon blockade. Here, we propose a photon blockade scheme composed of a weakly second-order nonlinear medium with an optical parametric amplification in a low-frequency cavity. Unlike the traditional weakly coupled system, the effective coupling strength in the proposed scheme can be significantly higher than the decay rate of the cavity mode. This can be achieved by adjusting the squeezing parameter even if the original coupling strength is weak. The thermal noise of the squeezed cavity mode can be suppressed by a squeezed vacuum field. Using a probability amplitude method, we obtain the optimal condition of photon blockade in the steady-state. By solving the master equation numerically in the steady-state, a strong photon antibunching effect that is consistent with the optimal conditions can be obtained in the cavity with low frequency. Besides, the photon blockade phenomenon and cross-correlation of two cavities can be significantly enhanced under a specific squeezing parameter. Our results may be useful for future studies on the characteristics of photon statistics.

Ground-state cooling of mechanical oscillator via quadratic optomechanical coupling with two coupled optical cavities.

We present a scheme for the electromagnetically induced transparency (EIT)-like nonlinear ground-state cooling in a double-cavity optomechanical system in which an optical cavity mode is coupled parametrically to the square of the position of a mechanical oscillator, an additional auxiliary cavity is coupled to the optomechanical cavity. The optimum cooling conditions is derived, based on which the heating process can be well suppressed and the mechanical resonator can be cooled with an optimal effect to near its ground state through EIT-like cooling mechanism even in unresolved sideband regime. It is demonstrated by numerical simulations that not only the average phonon number of steady state is lower than that of single-cavity optomechanical system, but also the cooling rate is greatly faster than that of the linear optomechanical coupling due to the two-phonon cooling process in the quadratic coupling. Also, the ground-state cooling is achievable even with a relatively weak quadratic coupling strengthby tunning the coupling between two cavities to reach the optimum cooling conditions, thus provides an solution for overcoming the limitations of weak quadratic coupling rate in experiments. The proposed approach provides a platform for quantum manipulation of macroscopic mechanical devices beyond the resolved sideband limit and linear coupling regime.

MiR-223 regulates proliferation and apoptosis of IL-22-stimulated HaCat human keratinocyte cell lines via the PTEN/Akt pathway.

Psoriasis, a chronic inflammatory skin disorder disease, is closely associated with hyperproliferation of keratinocytes. Upregulated miR-223 has been found in peripheral blood mononuclear cells from patients with psoriasis and from psoriatic skin. However, its role in keratinocytes remains unknown. We thus aimed to investigate the function of miR-223 in psoriasis. Interleukin-22 (IL-22) is a crucial keratinocyte trigger in the T-cell-mediated immune response to psoriasis. We found miR-223 to be overexpressed in psoriatic lesions and in IL-22-stimulated HaCaT cells. HaCaT cells then were transfected with a miR-223 mimic or inhibitor to overexpress or inhibit expression of miR-223, respectively. A Cell Counting Kit-8 assay revealed that miR-223 overexpression promoted and miR-223 downregulation inhibited proliferation in IL-22-stimulated HaCaT cells. Flow cytometry analysis certified that miR-223 overexpression decreased HaCaT cell apoptosis, whereas miR-223 downregulation increased it. A dual-luciferase reporter assay demonstrated that miR-223 directly targeted the phosphatase and tensin homolog (PTEN) gene. MiR-223 also negatively regulated mRNA and protein expression of PTEN and modulated the PTEN/Akt pathway in IL-22-stimulated HaCaT cells. PTEN silencing attenuated the activity of the miR-223 inhibitor in these cells via the PTEN/Akt pathway. Overall, the results showed that miR-223 increased proliferation and inhibited apoptosis of IL-22-stimulated keratinocytes via the PTEN/Akt pathway.

Pulmonary artery closure in combination with patch technique for treating congenital heart disease combined with large patent ductus arteriosus: A clinical study of 9 cases.

OBJECTIVE: To document clinical experience of treating congenital heart disease combined with large patent ductus arteriosus with pulmonary artery closure in combination with patch technique. METHODS: Thirty-six patients (8 males and 28 females) who suffered from congenital heart disease and underwent hybrid surgery in the First Affiliated Hospital of Zhengzhou University from October 2010 to February 2014 were selected for this study. They aged 14 to 39 years and weighed 32.20 to 61.50 kg. Diameter of arterial duct was between 10 mm and 13 mm; 28 cases were tube type, 4 cases were funnel type and four cases were window type. All patients had moderate or severe pulmonary arterial hypertension; besides, there were 28 cases of ventricular septal defect, 16 cases of atrial septal defect, eight cases of aortic insufficiency, four cases of mitral stenosis and insufficiency and four cases of infectious endocarditis. Cardz Pulmonary Bypass (CPB) was established after chest was opened along the middle line. With the help of Transesophageal echocardiography, large patent ductus arteriosus was blocked off through pulmonary artery. Pulmonary artery was cut apart after blocking of heart. Large patent ductus arteriosus on the side of pulmonary artery was strengthened with autologous pericardial patch. RESULTS: Of 36 patients, 32 patients had patent ductus arteriosus closure device and four patients had atrial septal defect closure device. Pulmonary arteries of 36 cases were all successfully closed. Systolic pressure declined after closure ((54.86±19.23) mmHg vs (96.05±23.07) mmHg, p<0.05); average pulmonary arterial pressure also declined after closure ((39.15±14.83) mmHg vs (72.88±15.76) mmHg, p<0.05). The patients were followed up for one to fifty one months (average 11.5 months). Compared to before surgery, left atrial diameter, left ventricular diameter and pulmonary artery diameter all narrowed after surgery. Besides, clinical symptoms were relieved and cardiac function of the patients also improved. CONCLUSION: Hybrid surgery is feasible and safe in treating patients with large patent ductus arteriosus and congenital heart disease, which decreases surgical problems, shortens surgical time and lowers the incidence of complications.

Removal of Pb2+, Hg2+, and Cu2+ by Chain-Like Fe3O4@SiO2@Chitosan Magnetic Nanoparticles.

In this paper, the chain-like core-shell structure Fe3O4@SiO2@Chitosan composite nanoparticles were synthesized by a two-step coating and following crosslinking glutaraldehyde on chitosan shell. The composite particles showed nearly monodisperse 105 sized particles with a core diameter of 80 nm and chitosan shell thickness of 12 nm. The synthesis conditions of the product were studied, and the morphology and properties of the composite nanoparticles were characterized by IR, XRD, TEM, SEM, EDS and VSM. The adsorption properties of Hg2+, Pb2+ or Cu2+ ions on Fe3O4, Fe3O4@SiO2 and the composite particles were in detail studied using the colorimetric method based on forming colored mercuric dithizone, rhodamine-Pb2+ complex and DDTC-Cu(2+) complex. The results showed, adsorption isotherm, kinetics and separation coefficient of heavy metal ions on these three magnetic nanoparticles were concerned with pH, metal ions' electronic configuration, silica coating and chitosan shell respectively. In addition, the recycle efficiency was also studied. The findings demonstrated that Fe3O4@SiO2@Chitosan composite nanoparticles have great application value in the adsorption and separation of heavy metal ions.

Right coronary artery fistula misdiagnosed as right atrial cardiac myxoma: A case report.

The current study describes a case of right coronary artery fistula (CAF) misdiagnosed as right atrial myxoma (RAM). A 33-year-old man presented with a 13-year history of intermittent chest pain, and aggravation for 3 days. Echocardiography revealed an occupying lesion in the right atrium producing a partial dynamic tricuspid obstruction. The initial diagnosis was RAM, which causes partial right ventricular inflow tract obstruction. During cardiopulmonary bypass surgery, a giant mass was detected in the anterior wall of the right ventricle and an abnormal vascular fistula was observed at the bottom of the mass. Successful excision of the mass and closure of the fistula completely relieved the patient's presenting symptoms. The disease was subsequently diagnosed as right CAF draining to the myocardial void. The surgical management and misdiagnosis of the case are discussed herein.

Cagelike mesoporous silica encapsulated with microcapsules for immobilized laccase and 2, 4-DCP degradation.

In this study, cage-like mesoporous silica was used as the carrier to immobilize laccase by a physical approach, followed by encapsulating with chitosan/alginate microcapsule membranes to form microcapsules of immobilized laccase based on layer-by-layer technology. The relationship between laccase activity recovery/leakage rate and the coating thickness was simultaneously investigated. Because the microcapsule layers have a substantial network of pores, they act as semipermeable membranes, while the laccase immobilized inside the microcapsules acts as a processing plant for degradation of 2,4-dichlorophenol. The microcapsules of immobilized laccase were able to degrade 2,4-dichlorophenol within a wide range of 2,4-dichlorophenol concentration, temperature and pH, with mean degradation rate around 62%. Under the optimal conditions, the thermal stability and reusability of immobilized laccase were shown to be improved significantly, as the removal rate and degradation rate remained over 40.2% and 33.8% respectively after 6cycles of operation. Using mass spectrometry (MS) and nuclear magnetic resonance (NMR), diisobutyl phthalate and dibutyl phthalate were identified as the products of 2,4-dichlorophenol degradation by the microcapsules of immobilized laccase and laccase immobilized by a physical approach, respectively, further demonstrating the degradation mechanism of 2,4-dichlorophenol by microcapsule-immobilized laccase.