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We propose a new test for structural changes in large dimensional factor models via a discrete Fourier transform (DFT) approach. If structural changes occur, the conventional principal component analysis fails to estimate common factors and factor loadings consistently. The estimated residuals will contain information about structural changes. Therefore, we can compare the DFT of the estimated residuals with the null (zero) spectrum implied by no structural change. The proposed test is powerful against both smooth structural changes and abrupt structural breaks with a possibly unknown number of breaks and unknown break dates in factor loadings. It can detect a class of local alternatives at the parametric rate. As a result, the test is asymptotically more efficient than the existing tests in the factor model literature. And our test is also robust to serial and cross-sectional dependence of unknown form without having to estimate any long-run variance-covariance matrix. Moreover, it is easy to implement and tuning parameter-free. Monte Carlo studies demonstrate its reasonable size and excellent power in detecting various forms of structural changes in factor loadings. In an application to the U.S. macroeconomic data, we find significant and robust evidence of time-varying factor loadings.

Ketamine is a noncompetitive antagonist of N-methyl-D-aspartate receptors (NMDARs). We have shown that ketamine can induce cognitive impairments and schizophrenia-like symptoms in mice. However, the detailed metabolic profile changes in the progression of ketamine-induced schizophrenia-like symptoms are still not fully elucidated. In this study, an ultra-performance liquid chromatography-Q-Exactive hybrid quadrupole-Orbitrap mass spectrometry-based untargeted hippocampus high-throughput metabolomics method was first performed to screen for potential biomarkers in a schizophrenia-like state in a chronically administered ketamine-induced mouse model. Our results identified that the amino acid and energy metabolism pathways were significantly affected in mouse models of ketamine-induced schizophrenia. The detailed amino acid profiles were subsequently quantified in the hippocampus. The results showed that ketamine dramatically decreased the Lys, Gly, and Ser levels while significantly increasing the Gln level and relative Glu-to-GABA ratio. Our study suggested that Gln, Gly and Ser metabolism disturbances might be involved in ketamine-induced schizophrenia-like phenotypes. This research offers a fresh viewpoint for creating new neuroleptic medications and contributes to understanding the mechanisms underlying ketamine-induced schizophrenia.

Abiotic stress, a major factor limit growth and productivity of major crops. Orchardgrass is one of the most important cool-season forage grasses in the world, and it is highly tolerant to abiotic stress. The MADS-box transcription factor family is one of the largest families in plants, and it plays vital roles in multiple biological processes. However, MADS-box transcription factors in orchardgrass, especially those involved in abiotic stress, have not yet been elucidated. Here, 123 DgMADS-box members were identified in orchardgrass and a detailed overview has been presented. Syntenic analysis indicated that the expansion of the DgMADS-box genes in orchardgrass is mainly dependent on tandem duplication events. Some DgMADS-box genes were induced by multiple abiotic stresses, indicating that these genes may play critical regulatory roles in orchardgrass response to various abiotic stresses. Heterologous expression showed that DgMADS114 and DgMADS115 could enhance stress tolerance of transgenic Arabidopsis, as revealed by longer root length or higher survival rates under PEG, NaCl, ABA, and heat stress. The results of this study provide a scientific basis for clarifying the functional characterization of MADS-box genes in orchardgrass in response to environmental stress can be further used to improve forages and crops via breeding programs.

What are the potential clinical benefits of embryo culture and assessment in a time-lapse incubator compared with a standard incubator using static assessment?This large multicentre, single-blinded, randomized controlled study included 1224 participants randomly assigned (1:1) to the time-lapse or standard incubator group. In all patients one or two embryos were transferred on day 3. The primary outcome was the implantation rate in the first embryo transfer cycle. Secondary outcomes included the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate.Among 1224 participants recruited, 1182 underwent embryo transfer. The number of successfully implanted embryos in the first transfer cycle was significantly higher in the time-lapse incubator group (time-lapse group: 52.35%, standard incubator group: 47.11%, P = 0.014). The implantation rate in the first embryo transfer cycle was still significantly higher in the time-lapse group than the standard incubator group after adjusting for age, body mass index, medical centre and embryo status (relative risk 1.11, 95% confidence interval 1.02-1.20, P = 0.020). However, the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate were not statistically different between the groups.The implantation rate in the first embryo transfer cycle was significantly improved in the time-lapse group, but the effect of the time-lapse system on the cumulative implantation rate or cumulative live birth rate was not significant. The embryo assessment method offered by time-lapse systems rather than an undisturbed environment may play an important role in improving the implantation rate in the first embryo transfer cycle. These results are only applicable to young patients.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to unprecedented social and economic disruption. Many nucleic acid testing (NAT) laboratories in China have been established to control the epidemic better. This proficiency testing (PT) aims to evaluate the participants' performance in qualitative and quantitative SARS-CoV-2 NAT and to explore the factors that contribute to differences in detection capabilities. Two different concentrations of RNA samples (A, B) were used for quantitative PT. Pseudovirus samples D, E (different concentrations) and negative sample (F) were used for qualitative PT. 50 data sets were reported for qualitative PT, of which 74.00% were entirely correct for all samples. Forty-two laboratories participated in the quantitative PT. 37 submitted all gene results, of which only 56.76% were satisfactory. For qualitative detection, it is suggested that laboratories should strengthen personnel training, select qualified detection kits, and reduce cross-contamination to improve detection accuracy. For quantitative detection, the results of the reverse transcription digital PCR (RT-dPCR) method were more comparable and reliable than those of reverse transcription quantitative PCR (RT-qPCR). The copy number concentration of ORF1ab and N in samples A and B scattered in 85, 223, 50, and 106 folds, respectively. The differences in the quantitative result of RT-qPCR was mainly caused by the non-standard use of reference materials and the lack of personnel operating skills. Comparing the satisfaction of participants participating in both quantitative and qualitative proficiency testing, 95.65% of the laboratories with satisfactory quantitative results also judged the qualitative results correctly, while 85.71% of the laboratories with unsatisfactory quantitative results were also unsatisfied with their qualitative judgments. Therefore, the quantitative ability is the basis of qualitative judgment. Overall, participants from hospitals reported more satisfactory results than those from enterprises and universities. Therefore, surveillance, daily qualitiy control and standardized operating procedures should be strengthened to improve the capability of SARS-CoV-2 NAT.

Pathological vascular remodeling and cell proliferation play vital roles in many proliferative vascular diseases. Estrogen can protect the cardiovascular system, but its exact molecular mechanism is unknown. Here we report that 17β-estradiol (E2) suppressed vascular smooth muscle cells (VSMCs) proliferation and inflammation. qRT-PCR and Western blot demonstrated that E2 decreased NF-κB p50 expression and reduced VSMCs proliferation and inflammation. Mechanistically, a dual luciferase reporter assay and chromatin immunoprecipitation suggested that KLF5 promoted NF-κB p50 expression by binding to the NF-κB p50 promoter, whereas E2 reduced the effect of KLF5 binding to the NF-κB p50 promoter and inhibited NF-κB p50 expression. Furthermore, a coimmunoprecipitation assay and immunofluorescence staining showed that the interaction between KLF5 and ERα increased in VSMCs treated with E2, which in turn decreased NF-κB p50 expression levels. Altogether, we reveal that E2 inhibits VSMCs proliferation and inflammation by reducing NF-κB expression induced by an increased interaction between KLF5 and ERα. These data provide further insights into how E2 inhibits vascular proliferation and inflammation.

Type 2 diabetes mellitus (T2DM) is a well-established risk factor for cardiovascular diseases. We aimed to identify the biological variation of ten cardiovascular biochemical markers in T2DM patients to aid in their interpretation.Blood samples for evaluating ten biomarkers were collected biweekly from 23 T2DM patients (10 men, 13 women) for three months. The analytical variability and variations of within-subject (CVThe levels of total cholesterol (CHOL), apolipoprotein A (apoA), homocysteine (HCY), high-sensitivity troponin T (hsTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) differed between males and females (P 0.05). The CVThe cardiovascular biochemical markers in T2DM patients showed higher CV

Postoperative cognitive decline (POCD) is a common complication after surgery and anesthesia among the elderly. Yet the potential mechanism of POCD remains ambiguous, with limited therapeutic measures currently available. Ketamine has been reported to attenuate POCD after cardiac surgery. Herein, we tried to determine the effect of esketamine (the S-enantiomer of ketamine) on POCD and the possible molecular mechanisms.We investigated the effects of esketamine (10 mg/kg) on POCD using an exploratory laparotomy model in aged SD rats (24 months). Open field, novel object recognition, and morris water maze tests were performed on day 30 post-surgery. 24 h or 30 d post-surgery, brain tissue from the hippocampus and ventromedial prefrontal cortex (vmPFC) was harvested and subjected to histopathology and molecular biology analysis. During the in vitro experiment, primary astrocytes from the hippocampus and vmPFC were exposed to lipopolysaccharide (LPS) to investigate the pathological changes in astrocytes during the process of POCD.Our results indicated that exploratory laparotomy could induce significant cognitive and memory decline, accompanied by A2-type astrocytes phenotype loss and increased expression of neuron Aβ-42, astrocytes GABA, stimulator of interferon genes (STING) and TANK-binding kinase 1 (TBK1). In addition, LPS exposure significantly decreased the mitochondrial membrane potential and upregulated the level of pyroptosis-associated proteins, including cleaved caspase-1 and IL-18. Notably, treatment with esketamine reversed these abnormalities in vivo and vitro. However, ADU-S100, a special STING activator, suppressed the protective effects of esketamine to a certain extent. Finally, C-176, an antagonist of STING, further enhanced the protective effects of esketamine against POCD.Findings of our study suggest that esketamine can alleviate surgery-induced POCD in rats via inhibition of the STING/TBK1 signaling pathway.

Current research on the effects of mindfulness therapy on MCI and insomnia has been inconsistent. It is still a hot topic of research and discussion. This study aimed to improve the sleep quality, cognition, and mental state of patients with mild cognitive impairment (MCI) with insomnia.A double-blind randomized controlled trial was conducted. Seventy-five patients who met the eligibility criteria were randomly assigned to the mindfulness (n = 38) or health education (n = 37) treatment group. The primary outcomes were sleep, measured by the Pittsburgh Sleep Quality Inventory, and cognition, measured by The Montreal Cognitive Assessment and Mini-Mental State Examination. Secondary outcomes included insomnia, measured by the Insomnia Severity Index, depression, anxiety, and perceived stress. EEG signals were collected at rest with eyes closed in the mindfulness state. The power spectrum was analyzed from these data.Cognitive function and sleep quality were significantly improved in the mindfulness group (95% confidence interval 0.04 - 0.05, 0.03 - 0.04, -5.58 - -1.55, respectively). Anxiety and perceived stress scores were significantly lower than those in the control group (95% confidence interval 0.002 - 0.004, 0.009 - 0.013, respectively). The power spectrum differences in δ, θ, β, and γ bands were significant between the rest and mindfulness states (P .05). Good safety was achieved in both groups with no deaths or serious adverse events.Mindfulness improved sleep quality, cognitive function, and mentality of patients. Mindfulness practice caused deep relaxation in the brain and changes in electrical frequency bands associated with attention and cognitive tasks. Mindfulness learning can be performed successfully for individuals with MCI. Additionally, it is suitable for adoption in nursing homes.

The non-SMC condensin I complex subunit G (NCAPG) is a subunit of the condensin complex, many studies have shown that NCAPG is aberrantly expressed in different tumors and closely associated with poor prognosis, but its role in bladder cancer is unclear. In this paper, we found that NCAPG expression was upregulated in bladder cancer in tumor-related databases, and further verified the expression of NCAPG in bladder cancer tissues as well as bladder cancer cell lines by tissue microarray, qPCR, and WB. Next, we explored the changes in bladder cancer cell proliferation as well as migration after NCAPG knockdown by cell growth curve, colony formation, soft agar assay, and xenograft model. Finally, we examined the changes in downstream signaling pathways after NCAPG knockdown using RNA-Seq, and we found that the NF-κB signaling pathway was inhibited with NCAPG gene knockdown, which was verified by luciferase reporter assay as well as WB. In conclusion, our results illustrate that NCAPG knockdown can inhibit the proliferation of bladder cancer cells through the NF-κB signaling pathway. This finding demonstrates that NCAPG could be a potential target for the treatment of bladder cancer.

PLEKHF2 proteins are widespread in animals, but their functions and mechanisms remain poorly defined. Here we clearly demonstrate that PLEKHF2 is a newly identified present abundantly in the eggs/embryos of zebrafish. We also show that recombinant PLEKHF2 acts as a pattern recognition receptor capable of identifying the bacterial signature molecule PGN, LPS, and LTA, binding the bacteria, and functions as an antibacterial effector directly killing the bacteria. In brief, these results indicate that PLEKHF2 is an antibacterial protein, a novel role assigned to PLEKHF2 proteins.

Metal organophosphonates have been explored in energy-related fields due to their high chemical and thermal stability as a type of uniformly precursor, but only few of pristine metal organophosphonate are directly used for oxygen evolution reaction (OER) catalysts. Here, a mixed-valence iron phosphonate (Fe3-ppat) has been constructed and applied to OER catalysis considered the potential active sites in pillars FeII(H2O)4(COO)2 and inorganic layers FeIII(μ2–OH)PO3. Specifically, isostructural trimetallic framework Fe1.7Co0.3Ni1.0-ppat possesses a minimum overpotential (291 mV), small Tafel slope (91.65 mV dec−1), and high stability up to 83 h. The enhanced catalytic performance could be mainly ascribed to the synergistic effect of NiII equivalent occupancy in pillars and Co/FeIII in layers.

We conducted a comparative study of the COVID-19 epidemic in three different settings: mainland China, the Guangdong province of China and South Korea, by formulating two disease transmission dynamics models which incorporate epidemic characteristics and setting-specific interventions, and fitting the models to multi-source data to identify initial and effective reproduction numbers and evaluate effectiveness of interventions. We estimated the initial basic reproduction number for South Korea, the Guangdong province and mainland China as 2.6 (95% confidence interval (CI): (2.5, 2.7)), 3.0 (95%CI: (2.6, 3.3)) and 3.8 (95%CI: (3.5,4.2)), respectively, given a serial interval with mean of 5 days with standard deviation of 3 days. We found that the effective reproduction number for the Guangdong province and mainland China has fallen below the threshold 1 since February 8th and 18th respectively, while the effective reproduction number for South Korea remains high until March 2nd Moreover our model-based analysis shows that the COVID-19 epidemics in South Korean is almost under control with the cumulative confirmed cases tending to be stable as of April 14th. Through sensitivity analysis, we show that a coherent and integrated approach with stringent public health interventions is the key to the success of containing the epidemic in China and especially its provinces outside its epicenter. In comparison, we find that the extremely high detection rate is the key factor determining the success in controlling the COVID-19 epidemics in South Korea. The experience of outbreak control in mainland China and South Korea should be a guiding reference for the rest of the world.

Introduction Establishing intravenous access is essential but may be difficult to achieve for patients requiring isolation for SARS-CoV-2 infection. This study aimed to investigate the effectiveness of infrared vein visualizer on the peripheral intravenous catheter therapy in COVID-19 patients. Methods A nonrandomized clinical trial was performed. One-hundred and twenty-two COVID-19 patients that required peripheral intravenous cannulation were divided into two groups with 60 in the control group and 62 in the intervention group. Conventional venipuncture method was applied to the control group while infrared vein imaging device was applied in the intervention group. The first attempt success rate, total procedure time and patients’ satisfaction score were compared between two groups using chi-square, t-test, and z-test (also known as Mann-Whitney U test) statistics. Results The first attempt success rate in the intervention group was significantly higher than that of control group (91.94% vs 76.67%, ꭓ2=5.41, P=0.02). The procedure time was shorter in the intervention group (M=211.44, SD=68.58 seconds vs M=388.27, SD=88.97 seconds, t=12.27, P