eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

Establishment and characterization of Lesch-Nyhan syndrome rabbit model.

Lesch-Nyhan syndrome (LNS) is a congenital defect disease that results in defective purine metabolism. It is caused by pathogenic variants of the HPRT gene. Its clinical symptoms mainly include high uric acid levels, gout, and kidney stones and damage. The mechanism of LNS has not been fully elucidated, and no cure exists. Animal models have always played an important role in exploring causative mechanisms and new therapies. This study combined CRISPR/Cas9 and microinjection to knock out the HPRT gene to create an LNS rabbit model. A sgRNA targeting exon 3 of HPRT gene was designed. Subsequently, Cas9 mRNA and sgRNA were injected into rabbit zygotes, and injected embryos were transferred to the uterus. The genotype and phenotype of rabbits were analyzed after birth. Four infant rabbits (named R1, R2, R3 and R4), which showed varying levels of gene modification, were born. The gene-editing efficiency was 100%. No wild-type sequences at the target HPRT gene were detected in R4 rabbit. Next, 6-thioguanine drug testing confirmed that HPRT enzymatic activity was deficient in R4 infant rabbit. HE staining revealed kidney abnormalities in all infant rabbits. Overall, an sgRNA capable of knocking out the HPRT gene in rabbits was successfully designed, and HPRT gene-modified rabbits were successfully constructed by using CRISPR/Cas9 technology and microinjection. This study provides a new nonrodent animal model for studying LNS syndrome.

Rogue wave generation using a chaotic semiconductor laser with energy redistribution.

We demonstrate for the first time that optical rogue waves (RWs) can be generated using a chaotic semiconductor laser with energy redistribution. Chaotic dynamics are numerically generated using the rate equation model of an optically injected laser. The chaotic emission is then sent to an energy redistribution module (ERM) that consists of a temporal phase modulation and a dispersive propagation. The process enables a temporal energy redistribution of the chaotic emission waveforms, where coherent summation of consecutive laser pulses leads to random generation of giant intensity pulses. Efficient generation of optical RWs are numerically demonstrated by varying the ERM operating parameters in the entire injection parameter space. The effects of the laser spontaneous emission noise on the generation of RWs are further investigated. The RW generation approach offers a relatively high flexibility and tolerance in the choice of ERM parameters according to the simulation results.

Cortical responses correlate with speech performance in pre-lingually deaf cochlear implant children.

Introduction: Cochlear implantation is currently the most successful intervention for severe-to-profound sensorineural hearing loss, particularly in deaf infants and children. Nonetheless, there remains a significant degree of variability in the outcomes of CI post-implantation. The purpose of this study was to understand the cortical correlates of the variability in speech outcomes with a cochlear implant in pre-lingually deaf children using functional near-infrared spectroscopy (fNIRS), an emerging brain-imaging technique. Methods: In this experiment, cortical activities when processing visual speech and two levels of auditory speech, including auditory speech in quiet and in noise with signal-to-noise ratios of 10 dB, were examined in 38 CI recipients with pre-lingual deafness and 36 normally hearing children whose age and sex matched CI users. The HOPE corpus (a corpus of Mandarin sentences) was used to generate speech stimuli. The regions of interest (ROIs) for the fNIRS measurements were fronto-temporal-parietal networks involved in language processing, including bilateral superior temporal gyrus, left inferior frontal gyrus, and bilateral inferior parietal lobes. Results: The fNIRS results confirmed and extended findings previously reported in the neuroimaging literature. Firstly, cortical responses of superior temporal gyrus to both auditory and visual speech in CI users were directly correlated to auditory speech perception scores, with the strongest positive association between the levels of cross-modal reorganization and CI outcome. Secondly, compared to NH controls, CI users, particularly those with good speech perception, showed larger cortical activation in the left inferior frontal gyrus in response to all speech stimuli used in the experiment. Discussion: In conclusion, cross-modal activation to visual speech in the auditory cortex of pre-lingually deaf CI children may be at least one of the neural bases of highly variable CI performance due to its beneficial effects for speech understanding, thus supporting the prediction and assessment of CI outcomes in clinic. Additionally, cortical activation of the left inferior frontal gyrus may be a cortical marker for effortful listening.

Thermochromic Ni(II) Organometallics With High Optical Transparency and Low Phase-Transition Temperature for Energy-Saving Smart Windows.

Thermochromic smart windows with rational modulation in indoor temperature and brightness draw considerable interest in reducing building energy consumption, which remains a huge challenge to meet the comfortable responsive temperature and the wide transmittance modulation range from visible to near-infrared (NIR) light for their practical application. Herein, a novel thermochromic Ni(II) organometallic of [(C2 H5 )2 NH2 ]2 NiCl4 for smart windows is rationally designed and synthesized via an inexpensive mechanochemistry method, which processes a low phase-transition temperature of 46.3 °C for the reversible color evolution from transparent to blue with a tunable visible transmittance from 90.5% to 72.1%. Furthermore, cesium tungsten bronze (CWO) and antimony tin oxide (ATO) with excellent NIR absorption in 750-1500 and 1500-2600 nm are introduced in the [(C2 H5 )2 NH2 ]2 NiCl4 -based smart windows, realizing a broadband sunlight modulation of a 27% visible light modulation and more than 90% of NIR shielding ability. Impressively, these smart windows demonstrate stable and reversible thermochromic cycles at room temperature. Compared with the conventional windows in the field tests, these smart windows can significantly reduce the indoor temperature by 16.1 °C, which is promising for next-generation energy-saving buildings.

Effects of Holliday Junction-Recognition Protein-Mediated C-Jun N-Terminal Kinase/ Signal Transducer and Activator of Transcription 3 Signaling Pathway on Cell Proliferation, Cell Cycle and Cell Apoptosis in Bladder Urothelial Carcinoma.

The Holliday Junction-Recognition Protein (HJURP) was upregulated in several tumors, which was associated with poor outcome. This study investigated the effects of the HJURP-mediated c-Jun N-terminal kinase (JNK)/ signal transducer and activator of transcription 3 (STAT3) pathway on bladder urothelial carcinoma (BLUC). Online databases were used to analyze HJURP expression in BLUC and the correlation of HJURP to JNK1 [mitogen-activated protein kinase 8 (MAPK8)], JNK2 (MAPK9), STAT3, marker of proliferation Ki-67 (MKI67), proliferating cell nuclear antigen (PCNA), cyclin dependent kinase 2 (CDK2), CDK4 and CDK6. HJURP expression was detected in BLUC cells and human normal primary bladder epithelial cells (BdECs). BLUC cells were treated with HJURP lentivirus activation /shRNA lentivirus particles or JNK inhibitor SP600125. HJURP was upregulated in BLUC tissues and correlated with poor prognosis of patients (all P < 0.05). HJURP in tumor positively correlated with MAPK8 (R = 0.30), MAPK9 (R = 0.30), STAT3 (R = 0.15), MKI67 (R = 0.60), PCNA (R = 0.46), CDK2 (R = 0.39), CDK4 (R = 0.24) and CDK6 (R = 0.21). The JNK inhibitor SP600125 decreased p-JNK/JNK and p-STAT3/STAT3 in BLUC cells, which was reversed by HJURP overexpression (P < 0.05). The HJURP-mediated JNK/STAT3 pathway promoted BLUC cell proliferation and inhibited cell apoptosis (P < 0.05). HJURP reversed the arrested G0/G1 phase of BLUC cells by SP600125. HJURP acted as an oncogene to regulate BLUC cell proliferation, apoptosis and the cell cycle by mediating the JNK/STAT3 pathway. Therefore, HJURP targeting might be an attractive novel therapeutic target for early diagnosis and treatment in BLUC.

Molecular dynamics simulation of adsorption and separation of xylene isomers by Cu-HKUST-1.

Metal-organic frameworks (MOFs) are widely used in the adsorption separation of various gases. A fundamental understanding of the effective separation of xylene isomers helps improve aromatic products' separation efficiency and reduce industrial separation costs. Grand Canonical Monte Carlo (GCMC) simulations combined with Molecular Science is widely used to predict gas adsorption and diffusion in single crystals with metal-organic frameworks. We performed a GCMC + MD combined approach to study xylene isomers' adsorption and separation in Cu-HKUST-1 to predict the permeability and selectivity of the ternary gas mixture in the MOF with the adsorption and diffusion usage data. Most current studies take into account the computational cost and difficulty. Most recent research models are limited to the adsorption of a single or specific molecule, such as hydrogen, methane, carbon dioxide, etc. For this reason, we report an attempt to study the adsorption separation of aromatic gases (p-xylene/o-xylene/m-xylene) based on Cu-HKUST-1 single-crystal materials based on some previous research methods with an appropriate increase in computational cost. To predict the adsorption selectivity and permeability of the ternary mixture of xylene isomers on the MOF surface, the model simulation calculates key parameters of gas adsorption, including gas adsorption volume (N), the heat of adsorption (Q st), Henry coefficient (K), and diffusion coefficient (D).

Acupuncture for chronic sciatica: protocol for a multicenter randomised controlled trial.

BACKGROUND: Chronic Sciatica is a disabling condition causing considerable medical, social and financial implications. Currently, there is no recognised long-term effective treatment to alleviate sciatica. Acupuncture has been widely used for treating chronic pains with persistent analgesic effects. We aim to evaluate the efficacy and safety of acupuncture for chronic sciatica with follow-up in 52 weeks. METHODS AND ANALYSIS: This is a multicenter randomised sham-controlled trial. A total of 216 patients with chronic sciatica will be enrolled and randomly assigned to the acupuncture or sham acupuncture group. There will be 10 treatment sessions applied in 4 weeks with frequency decreased over time. Patients will complete follow-ups during 52 weeks. The primary outcomes are changes in leg pain intensity and disability from baseline to week 4. Secondary outcomes include back pain intensity, frequency and bothersomeness, quality of life, and global perceived effect. Adverse events will be recorded in detail. ETHICS AND DISSEMINATION: Ethical approval of this trial was granted from the ethics committee of Beijing University of Chinese Medicine and all study centres (No. 2020BZYLL0803). Written informed consent will be obtained from enrolled patients. Trial results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2100044585 (Chinese Clinical Trial Registry, http://www.chictr.org.cn, registered on 24 March 2021); preresults.

[Research progress on effective components and mechanisms of anti-depressive Chinese medicine].

Since the pathogenesis of depression is complicated, the therapeutic effects of western medicine are poor accompanied by severe side effects. Chinese medicine has unique advantages in the treatment based on syndrome differentiation and contains many effective components against depression, including flavonoids, terpenes, phenylpropanoids, quinones, and alkaloids. These chemical components can delay the course of the disease, improve the curative effect, and reduce side effects of western medicine by regulating the biochemical abnormalities of monoamine neurotransmitters, brain tissue protein content, and internal environment as well as energy metabolism to make the treatment of Chinese medicine highlighted and recognized. This study systematically reviewed the effective components and mechanisms of anti-depressive Chinese medicine to inspire the rational development and utilization of new Chinese medicines against depression.

Efficacy of acupuncture for sciatica: study protocol for a randomized controlled pilot trial.

BACKGROUND: Acupuncture is widely used for pain diseases while evidence of its efficacy for sciatica is insufficient. We aim to explore the feasibility and efficacy of acupuncture with different acupoint selecting strategies for sciatica induced by lumbar disc herniation. METHODS: This is a multicenter, three-arm, patient-assessor-blinded randomized controlled pilot trial. Ninety patients will be assigned randomly into 3 groups including disease-affected meridians (DAM) group, non-affected meridians (NAM) group, and sham acupuncture (SA) group in a 1:1:1 ratio. The trial involves a 4-week treatment along with follow-up for 22 weeks. The primary outcome is the change of leg pain intensity measured by the visual analogue scale (VAS) from baseline to week 4 after randomization. Secondary outcomes include functional status, back pain intensity, and quality of life. Adverse events will also be recorded. DISCUSSION: The results will inspire the optimal acupuncture strategy for sciatica and help establish a better design as well as power calculation for a full-scale study. TRIAL REGISTRATION: ChiCTR2000030680 (Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 9 March 2020).

Efficient All-Inorganic Perovskite Light-Emitting Diodes with Cesium Tungsten Bronze as a Hole-Transporting Layer.

The realization of high-performance optoelectronic devices requires excellent charge-transporting layers and efficient carrier recombination. Herein, we synthesized cesium tungsten bronze (Cs0.32WO3) nanocrystals and utilized them as the hole-transporting material to fabricate all-inorganic perovskite light-emitting diodes (PeLEDs). Due to the excellent carrier balance characteristics via comparison between the hole-only device and electron-only device, the all-inorganic PeLEDs with CsPbBr3 as the light-emitting layer present the maximum current efficiency of 31.51 cd/A and external quantum efficiency (EQE) of 8.48%, which are self-evidently enhanced compared with the PEDOT:PSS (14.78 cd/A, 4.03%) and WO3 (24.75 cd/A, 6.18%) based devices. Considering the remarkably improved device performance, the proposed HTL of Cs0.32WO3 is promising, acting as a favorable building block for high-efficiency light-emitting devices.

NEAT1 induces osteosarcoma development by modulating the miR-339-5p/TGF-ß1 pathway.

The long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) has been recognized as a tumor oncogene involved in the development of multiple cancers. However, the function of NEAT1 and its molecular mechanism in osteosarcoma (OS) remain unclear. First, we detected the NEAT1 expression in OS cell lines by performing quantitative reverse-transcription polymerase chain reaction. Next, the effects of NEAT1 on OS cell growth, apoptosis, migration, and invasion were tested by lentivirus-mediated downregulation. We observed that inhibition of NEAT1 restrained OS cell progression greatly. Interestingly, in the last few years, increasing studies have shown that some lncRNAs can act as miRNA sponges and reduce the amount of the same. Here, we found that NEAT1 can modulate OS development via sponging miR-339-5p. MiR-339-5p was significantly decreased in OS cells, and its overexpression can remarkably repress the OS proliferation. These results indicated that NEAT1 could function as a tumor oncogene in OS by inhibiting miR-339-5p in vitro. Then, the following assays validated that transforming growth factor ß1 (TGF-ß1) can act as a functional target of miR-339-5p in OS cells. Finally, we indicated that NEAT1 could mediate TGF-ß1 expression by competitively sponging miR-339-5p. NEAT1 induced OS cell proliferation and cell mobility by binding to miR-339-5p and increasing TGF-ß1 in OS. It was demonstrated in our study that lncRNA NEAT1 could impede miR-339-5p expression to maintain the expression of TGF-ß1, which led to the development of OS. Our findings implied that the novel identified NEAT1/miR-339-5p/TGF-ß1 axis might be a new molecular pathway or therapeutic target for OS diagnosis and treatment.

[Discussion on Clinical and Diagnosis Program of Integrative Medicine].

Facing current situation of integrative medicine (IM), authors put forward that clinical and diagnosis program of IM could be carried out from clinical path, pathogenesis, treatment theory and philosophy, and so on, but with different integration degrees. Meanwhile, formulation of concrete program should be disease-targetedly set up, and adjusted from person to person, from place to place, from time to time. As for settled IM program , authors could evaluate it from whether Chinese medicine and Western medicine have formed complementary, synergistic, excitatory actions, and toxicity attenuation; whether more problems could be solved in efficacy, safety, practicability, and economy than previous single mode.

Epigallocatechin­3­gallate inhibits the invasion of salivary adenoid cystic carcinoma cells by reversing the hypermethylation status of the RECK gene.

Epigallocatechin­3­gallate (EGCG) is an active and major constituent of green tea. As a non­nucleoside inhibitor of DNA methylation, EGCG is able to inhibit the hypermethylation of newly synthesised DNA, resulting in the reversal of hypermethylation and recovery in expression of the silenced genes. Reversion­inducing cysteine­rich protein with Kazal motifs (RECK) is a novel tumour suppressor gene, which negatively regulates matrix metalloproteinases, and inhibits tumour invasion, angiogenesis and metastasis. The present study aimed to examine the effects of EGCG on the methylation status of the RECK gene and tumour invasion in a salivary adenoid cystic carcinoma (SACC) cell line in vitro. Marked levels of methylated and weak levels of unmethylated RECK promoter were detected in the SACC83 cells, which was determined using methylation­specific polymerase chain reaction (PCR). In addition, the treatment of SACC83 cells with EGCG partially reversed the hypermethylation status of the RECK gene. Western blot analysis and reverse transcription­PCR demonstrated that EGCG significantly enhanced the protein and mRNA expression levels of RECK, and significantly reduced the invasive ability of the SACC83 cells, as determined using a Transwell assay. These results suggested that EGCG possesses novel anti­metastatic therapeutic potential for the treatment of SACC.

Correlations between Phlegm Syndrome of Chinese Medicine and Coronary Angiography: A Systematic Review and Meta-Analysis.

Phlegm is one of the most common patterns of coronary artery disease (CAD) in Chinese medicine. Our research was aimed at investigating the association between phlegm syndrome of CAD and coronary angiography (CAG) by meta-analysis. According to inclusion criteria, a total of 30 studies involving 5,055 CAD patients were included. The meta-analysis showed that phlegm syndrome patients were prone to multivessel disease (28 studies, OR = 1.53, 95% CI, 1.24 to 1.88, P < 0.01) and higher Gensini score (2 studies, OR = 5.90, 95% CI, 1.86 to 9.94, P = 0.004), but not obviously relevant to severe stenosis (≥75%) of coronary arteries (13 studies, OR = 1.20, 95% CI, 0.63 to 2.27, P = 0.57). We concluded that the coronary arteries lesions of CAD patients with phlegm syndrome were more severe than those with nonphlegm syndromes. Phlegm syndrome should, therefore, be regarded as a dangerous pattern of CAD with worse prognosis.

Topical cyclosporine A in the treatment of dry eye: a systematic review and meta-analysis.

PURPOSE: Cyclosporine A (CsA) is considered a potentially effective treatment for dry eye syndrome (DES), which is now one of the most common ocular problems whose exact mechanism is unknown. Because randomized controlled trials (RCTs) reported to date have shown varying results in the efficacy and safety of CsA in different types of DES, we conducted a systematic review and meta-analysis of RCTs on CsA versus placebo in treating DES to evaluate the treatment efficacy and safety of CsA. METHODS: We searched for RCTs published after 1990, in MEDLINE, EMBASE, the Cochrane library, and ClinicalTrials.gov. The RCTs that were included compared topical CsA and placebo for DES treatment by evaluating scores of ocular surface disease index, tear break-up time, or Schirmer test. Cochrane risk of bias tool was used for assessing the risk of bias. RESULTS: We included 12 RCTs involving 3034 eyes of 1660 participants. We observed statistically significant improvements on scores of break-up time (standardized mean difference [SMD], 0.80; 95% confidence interval [CI], 0.13-1.46; I = 95%) and scores of Schirmer test with anesthesia (SMD, 0.78; 95% CI, 0.09-1.46; I = 97%) after treatment with topical CsA. Scores of ocular surface disease index (SMD, 0.77; 95% CI, -1.05 to 2.58; I = 98%) and scores of Schirmer test without anesthesia (SMD, 0.08; 95% CI, -0.11 to 0.27; I = 0%) were not improved. Adverse events (odds ratio [OR], 1.61; 95% CI, 1.28-2.02; I = 21%) were observed. CONCLUSIONS: Topical CsA could be an effective treatment for DES, especially for DES associated with conjunctival injury. Further RCTs with larger sample sizes for different clinical types of DES are warranted to determine the efficacy and limitation for different clinical types of DES.

Molecular dynamics simulations of void defects in the energetic material HMX.

A molecular dynamics (MD) simulation was carried out to characterize the dynamic evolution of void defects in crystalline octahydro-1, 3, 5, 7-tetranitro-1, 3, 5, 7-tetrazocine (HMX). Different models were constructed with the same concentration of vacancies (10 %) to discuss the size effects of void. Energetic ground state properties were determined by annealing simulations. The void formation energy per molecule removed was found to be 55-63 kcal/mol(-1), and the average binding energy per molecule was between 32 and 34 kcal/mol(-1) according to the change in void size. Voids with larger size had lower formation energy. Local binding energies for molecules directly on the void surface decreased greatly compared to those in defect-free lattice, and then gradually increased until the distance away from the void surface was around 10 Å. Analysis of 1 ns MD simulations revealed that the larger the void size, the easier is void collapse. Mean square displacements (MSDs) showed that HMX molecules that had collapsed into void present liquid structure characteristics. Four unique low-energy conformers were found for HMX molecules in void: two whose conformational geometries corresponded closely to those found in HMX polymorphs and two, additional, lower energy conformers that were not seen in the crystalline phases. The ratio of different conformers changed with the simulated temperature, in that the ratio of α conformer increased with the increase in temperature.

Extraction, characterization and spontaneous gel-forming property of pectin from creeping fig (Ficus pumila Linn.) seeds.

Creeping fig (Ficus pumila Linn.) seeds can be manually rubbed and squeezed to produce a water extract (WE) that can gel at room temperature without any additives. Its gelling material, extraction behavior, and mechanism of spontaneous gel-formation were investigated. Gelling material was extracted from seeds using water, ammonium oxalate and hydrochloric acid, respectively. Results showed the main component of three extracts is low methoxyl pectin. The pectin locates in a transparent layer on the surface of seeds, as revealed by an inverted microscope. Hence, explained the feasibility of the squeezing and rubbing method in traditional handcraft. Comparing with the other methods, water-extracted pectin has high galacturonic acid content, viscosity-average molecular weight and intrinsic viscosity but low degree of methoxylation. This pectin forms the major component of WE, together with the high amount of calcium ions present in WE, it suggests the spontaneous gelation may be based on the 'egg-box' formation.