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Hydrogen sulfide (H2S) exerts an anti-atherosclerotic effect and decreases foam cell formation. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a key factor involved in foam cell formation. However, the association between H2S and Lp-PLA2 expression levels with respect to foam cell formation has not yet been elucidated. The present study investigated whether H2S can affect foam cell formation and potential signalling pathways via regulation of the expression and activity of Lp-PLA2. Using human monocytic THP-1 cells as a model system, it was observed that oxidized low-density lipoprotein (ox-LDL) not only upregulates the expression level and activity of Lp-PLA2, it also downregulates the expression level and activity of Cystathionine γ lyase. Exogenous supplementation of H2S decreased the expression and activity of Lp-PLA2 induced by ox-LDL. Moreover, ox-LDL induced the expression level and activity of Lp-PLA2 via activation of the p38MAPK signalling pathway. H2S blocked the expression levels and activity of Lp-PLA2 induced by ox-LDL via inhibition of the p38MAPK signalling pathway. Furthermore, H2S inhibited Lp-PLA2 activity by blocking the p38MAPK signaling pathway and significantly decreased lipid accumulation in ox-LDL-induced macrophages, as detected by Oil Red O staining. The results of the present study indicated that H2S inhibited ox-LDL-induced Lp-PLA2 expression levels and activity by blocking the p38MAPK signalling pathway, thereby improving foam cell formation. These findings may provide novel insights into the role of H2S intervention in the progression of atherosclerosis.

The beneficial effect of influenza vaccination (IV) in patients with diabetes was not completely understood.Using the research data of health insurance, we performed a cohort study of patients aged ≥20 years who were admitted to inpatient care due to diabetes in 2008-2013 in Taiwan. We performed the propensity score matching and the outcomes of complications and mortality following the diabetes admission was compared between patients with and without IV.Among 61,002 patients with diabetes admission, IV reduced 30-day in-hospital mortality (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.66-0.84), particularly among patients with prior diabetes hospitalization, inadequate control for diabetes, and diabetes-related comorbidities, such as eye involvement, ketoacidosis, renal manifestations, and coma. Compared with non-IV control group, patients with IV also had decreased risks of pneumonia (OR 0.92, 95% CI 0.87-0.97), septicemia (OR 0.83, 95% CI 0.79-0.88), urinary tract infection (OR 0.94, 95% CI 0.90-0.97), and intensive care (OR 0.29, 95% CI 0.27-0.31).In patients with diabetes admission, IV was associated with reduced risks of complications and mortality. Our study implicated the urgent need to promote influenza vaccination for this susceptible population with diabetes.

Cardiovascular disease (CVD) is still one of the most significant diseases and is a considerable threat to human health globally. PIWI-interacting RNAs (piRNAs) are novel small noncoding RNAs (ncRNAs) traditionally considered to be specifically expressed in the germline of many animal species and involved in the maintenance of germline stem cells and spermatogenesis. Although little is known about the origin and action of piRNAs and PIWI proteins in somatic cells, these molecules are emerging as readily available biomarkers for the diagnosis and treatment of cardiac injury and multiform CVD. Accumulating evidence reveals that piRNAs and PIWI proteins are associated with some molecular and cellular pathways in CVD. Here, we summarize recent evidence and evaluate the molecular mechanism of the involvement of piRNAs and PIWI proteins in CVD.

Thigmotaxis is required in small animals. In this study, we examined how the shelter angle affects the development of German cockroaches

Fourteen sesquiterpene lactones were isolated from the whole plant of Carpesium abrotanoides L. Their structures were determined on the basis of comprehensive spectroscopic data analysis. All compounds were screened for their cytotoxic activity, and compound 6 showed the strongest activity (IC50 2.73 − 7.21 µM) against five human cancer cell lines, including A549, HepG2, HCT116, MDA-MB-231, and CNE2. Compound 6 was further investigated. Compound 6 effectively induced G2/M cell cycle arrest and ROS accumulation in a dose-dependent manner, which further led to apoptosis in cancer cells. Interestingly, compounds 1 and 6 could also activate protective autophagy, which was reported for the first time in sesquiterpene isolated from Carpesium abrotanoides. In addition, compounds 1 and 6 could induce lysosomal biogenesis by 173.2% and 163.7%, respectively. In sum, sesquiterpene lactones from Carpesium abrotanoides could induce apoptosis and protective autophagy in cancer cells, which provide a serial of compounds with potential clinical applications.

Additional file 1: Table S1. Characteristics of surgical patients with atrial fibrillation. Table S2. Length of hospital stay and medical expenditures associated with CHA2DS2-VASc score in patients with atrial fibrillation. Table S3. Stratified analysis for risk of postoperative adverse events associated with CHA2DS2-VASc score in patients with atrial fibrillation.

Diabetic cardiomyopathy is an important irreversible chronic cardiovascular complication in diabetic patients. This condition is described as early diastolic dysfunction, myocardial fibrosis, cardiac hypertrophy, systolic dysfunction and other complex pathophysiological events, which ultimately lead to heart failure. Despite these characteristics, the underlying mechanisms resulting in diabetic cardiomyopathy are still unknown. With the developments in molecular biotechnology, increasing evidence shows that circRNAs play critical roles in the pathogenesis of diabetic cardiomyopathy. The purpose of this review is to summarize recent studies on the role of circRNAs in the pathophysiological process to provide novel prevention and treatment strategies for diabetic cardiomyopathy, oxidative stress, inflammation, endothelial dysfunction, myocardial fibrosis and cell death in diabetic cardiomyopathy.

IntroductionLimited information was available regarding the perioperative outcomes in patients with and without use of metformin. This study aims to evaluate the complications and mortality after major surgery in patients with diabetes who use metformin.Research design and methodsUsing a real-world database of Taiwan’s National Health Insurance from 2008 to 2013, we conducted a matched cohort study of 91 356 patients with diabetes aged >20 years who used metformin and later underwent major surgery. Using a propensity score-matching technique adjusted for sociodemographic characteristics, medical condition, surgery type, and anesthesia type, 91 356 controls who underwent surgery but did not use metformin were selected. Logistic regression was used to calculate the ORs with 95% CIs for postoperative complications and 30-day mortality associated with metformin use.ResultsPatients who used metformin had a lower risk of postoperative septicemia (OR 0.94, 95% CI 0.90 to 0.98), acute renal failure (OR 0.87, 95% CI 0.79 to 0.96), and 30-day mortality (OR 0.79, 95% CI 0.71 to 0.88) compared with patients who did not use metformin, in both sexes and in every age group. Metformin users who underwent surgery also had a decreased risk of postoperative intensive care unit admission (OR 0.60, 95% CI 0.59 to 0.62) and lower medical expenditures (pConclusionsAmong patients with diabetes, those who used metformin and underwent major surgery had a lower risk of complications and mortality compared with non-users. Further randomized clinical trials are needed to show direct evidence of how metformin improves perioperative outcomes.

Most legume plants can associate with diazotrophic soil bacteria called rhizobia, resulting in new root organs called nodules that enable N2 fixation. Nodulation is an energy-consuming process, and nodule number is tightly regulated by independent systemic signaling pathways controlled by CLE/SUNN and CEP/CRA2. Moreover, nitrate inhibits legume nodulation via local and systemic regulatory pathways. In Medicago truncatula, NLP1 plays important roles in nitrate-induced inhibition of nodulation, but the relationship between systemic and local pathways in mediating nodulation inhibition by nitrate is poorly understood. In this study, we found that nitrate induces CLE35 expression in an NLP1-dependent manner and that NLP1 binds directly to the CLE35 promoter to activate its expression. Grafting experiments revealed that the systemic control of nodule number involves negative regulation by SUNN and positive regulation by CRA2 in the shoot, and that NLP1's control of the inhibition of rhizobial infection, nodule development, and nitrogenase activity in response to nitrate is determined by the root. Unexpectedly, grafting experiments showed that loss of CRA2 in the root increases nodule number at inhibitory nitrate levels, probably because of CEP1/2 upregulation in the cra2 mutants, suggesting that CRA2 exerts active negative feedback regulation in the root., Root nodule formation is suppressed locally and systemically by nitrate. This study reports that NLP1 directly controls CLE35 in the root to systemically regulate nodulation in response to nitrate.

Monte Carlo simulation (MCS) is applied in the engineering with great fuzziness and uncertainty. Technique for order preference by similarity to an ideal solution (TOPSIS) method is used to deal with multi-criteria decision-making issue. Membership function is used to determine the membership degree of evaluated index. This paper presents the method for lake eutrophication level evaluation. The developed approach merges MCS method, TOPSIS method and membership function. The evaluated results are consistent with real eutrophication level in Lake Erhai, China. Global sensitivity analysis (GSA) is conducted. Results show that potassium permanganate index (CODMn) displays the highest negative correlation with the evaluated results and Secchi disc (SD) performs the highest positive correlation under different errors in measured data. The novelty of this work are: (1) the application of TOPSIS considers Surface water environmental quality standards and measured data. Besides, the Monte Carlo simulation method is applied to generate a normal distributed dataset to overcome the errors caused by human and equipment in data collection. The approach is utilized in the article, titled “Approach based on TOPSIS and Monte Carlo simulation methods to evaluate lake eutrophication levels” (Lin et al., 2020) [1].•Developed approach merges TOPSIS and MCS method.•It can increase the reliability of evaluated result., Graphical abstract Fig. 1. Distributions of evaluated index for lake eutrophication level.Image, graphical abstract

Background: It is still unclear if and to what extent antenatal or early postnatal or infants vitamin D supplementation would affect the development of allergy diseases later in life. Methods: Randomized controlled trials about vitamin D supplementation in pregnant or healthy children from birth to five years of age to prevent allergic diseases were selected. Descriptive and quantitative information was extracted. Relative risk estimates were synthesized under a fixed or random effects model. Heterogeneity was assessed by using the I2 metric. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to asses certainty of findings. MEDLINE(PubMed), EMBASE(OVID), and The Cochrane Central Register of Controlled Trials were searched up to March 1st 2020.Eligibility criteria for selecting studies: (1) the design was an randomized controlled trial(RCT); (2) healthy pregnant or lactating females and/or healthy children from birth to five years of age;(3) vitamin D protocol was specified in the treatment group; (4) outcomes were asthma/wheeze, allergic rhinitis, eczema(atopic dermatitis), food allergy and atopic sensitization; (5) the study contained relevant data to calculate the effect size. Results: In the present systematic review and meta-analysis, the available published randomized evidence on vitamin D supplementation in pregnant or infants for preventing allergic diseases across 7 RCTs were systematically assessed. Our meta-analysis showed that non-significant trends between vitamin D supplementation in pregnant or infants and the primary prevention of allergic diseases in offspring. The Grade quality assessment for all these conclusions indicated an evidence confidence level of low. Conclusions: In terms of practice implications, the data in this review should not make patients, doctors, and public health authorities confident that vitamin D supplementation in pregnant or infants or young children can primarily prevent allergic diseases. Systematic review registration: PROSPERO (CRD42020167747)

Solitary fibrous tumors are rare mesenchymal tumors that typically arise from the pleura and rarely originate from the mesentery. We herein report a case involving a 66-year-old patient who presented with a mass on the left abdomen. This mass had been incidentally noticed 10 years earlier. The patient sometimes experienced abdominal pain. Physical examination revealed an irregular mass, which was resected. A biopsy of the mass revealed that it was a solitary fibrous tumor originating from the mesentery of the small intestine. The patient was discharged 1 week after surgery and had an uneventful clinical course throughout the 4-month postoperative follow-up.

AIM To evaluate outcomes after major surgery in children and adolescents with intellectual disability. METHOD We used 2004 to 2013 claims data from Taiwan's National Health Insurance programme to conduct a nested cohort study, which included 220 292 surgical patients aged 6 to 17 years. A propensity score matching procedure was used to select 2173 children with intellectual disability and 21 730 children without intellectual disability for comparison. Logistic regression was used to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the postoperative complications and 30-day mortality associated with intellectual disability. RESULTS Children with intellectual disability had a higher risk of postoperative pneumonia (OR 2.16, 95% CI 1.48-3.15; p

Vascular calcification (VC), which is closely associated with significant mortality in cardiovascular disease, chronic kidney disease (CKD), and/or diabetes mellitus, is characterized by abnormal deposits of hydroxyapatite minerals in the arterial wall. The impact of oxidative stress (OS) on the onset and progression of VC has not been well described. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, xanthine oxidases, myeloperoxidase (MPO), nitric oxide synthases (NOSs), superoxide dismutase (SOD) and paraoxonases (PONs) are relevant factors that influence the production of reactive oxygen species (ROS). Furthermore, excess ROS-induced OS has emerged as a critical mediator promoting VC through several mechanisms, including phosphate balance, differentiation of vascular smooth muscle cells (VSMCs), inflammation, DNA damage, and extracellular matrix remodeling. Because OS is a significant regulator of VC, antioxidants may be considered as novel treatment options.

A series of muramyl dipeptide (MDP) analogues with structural modifications at the C4 position of MurNAc and on the d-iso-glutamine (isoGln) residue of the peptide part were synthesized. The C4-diversification of MurNAc was conveniently achieved by using CuAAC click strategy to conjugate an azido muramyl dipeptide precursor with structurally diverse alkynes. d-Glutamic acid (Glu), replaced with isoGln, was applied for the structural diversity through esterification or amidation of the carboxylic acid. In total, 26 MDP analogues were synthesized and bio-evaluated for the study of human NOD2 stimulation activity in the innate immune response. Interestingly, MDP derivatives with an ester moiety are found to be more potent than reference compound MDP itself or MDP analogues containing an amide moiety. Among the varied lengths of the alkyl chain in ester derivatives, the MDP analogue bearing the d-glutamate dodecyl (C12) ester moiety showed the best NOD2 stimulation potency.

Artificial light at night (ALAN) is a major driver of firefly population declines, but its physiological effects are not well understood. To investigate the impact of ALAN on firefly development, we exposed larval Aquatica ficta fireflies to ALAN for two weeks. High larval mortality was observed in the periods of 1-68 days and 106-134 days post-treatment, which may represent the short- and long-term impacts of ALAN. We then profiled the transcriptome of larval Aquatica ficta fireflies following two weeks of ALAN exposure. A total of 1262 (1.67% out of 75777 unigenes) were differentially expressed in the treatment group: 1157 were down-regulated, and 105 were up-regulated. Up-regulated unigenes were related to regulation of hormone levels, ecdysteroid metabolic process, and response to stimulus; down-regulated unigenes were related to negative regulation of insulin receptor signaling, germ cell development, oogenesis, spermatid development, and regulation of neuron differentiation. Transcriptome results suggest that the endocrine, reproductive, and neural development of firefly larvae could be impaired by even relatively brief period of ALAN exposure. This report contributes a much-needed molecular perspective to the growing body of research documenting the fitness impacts of ALAN on bioluminescent fireflies.

Adipose tissue (AT), a critical endocrine gland, is capable of producing and secreting abundant adipokines. Adipokines act on distant or adjacent organ tissues via paracrine, autocrine, and endocrine mechanism, which play attractive roles in the regulation of glycolipid metabolism and inflammatory response. Increasing evidence shows that adipokines can connect obesity with cardiovascular diseases by serving as promoters or inhibitors in vascular calcification. The chronic hypoxia in AT, caused by the adipocyte hypertrophy, is able to trigger imbalanced adipokine generation, which leads to apoptosis, osteogenic differentiation of vascular smooth muscle cells (VSMCs), vascular inflammation, and abnormal deposition of calcium and phosphorus in the vessel wall. The objectives of this review aim at providing a brief summary of the crucial influence of major adipokines on the formation and development of vascular calcification, which may contribute to better understanding these adipokines for establishing the appropriate therapeutic strategies to counteract obesity-associated vascular calcification.

Background and aims Limited information is available regarding the association between statins and pressure ulcers. The purpose of this study is to evaluate the beneficial effects of statins on pressure ulcers in stroke patients. Methods Using the claims data of Taiwan's National Health Insurance, we conducted a retrospective cohort study and identified new-onset stroke patients in 2000–2004. The propensity-score matching procedure was used to select eligible stroke patients with (n = 49,919) and without (n = 49,919) the use of statins. These two groups were followed until the end of 2009 to track the occurrence of pressure ulcers. Multivariate Cox proportional hazard models were conducted to calculate adjusted hazard rations (HRs) and 95% confidence intervals (CIs) of pressure ulcer associated with the use of statins. Results Stroke patients who used statins had a reduced risk of pressure ulcers during the follow-up period (HR 0.74, 95% CI 0.71–0.78). The association between statin use and a reduced risk of poststroke pressure ulcers was significant in men (HR 0.73, 95% CI 0.68–0.78), women (HR 0.75, 95% CI 0.71–0.80), and people aged more than 50 years. Use of lovastatin, pravastatin, rosuvastatin, atrovastatin, fluvastatin, and simvastatin was associated with reduced poststroke pressure ulcers. There was a dose-dependent decrease in the frequency of pressure ulcers with increasing quantities of statins used, from 1 prescription to ≥3 prescriptions. Conclusion We raised the possibility that use of statins was associated with reduced risk of pressure ulcers in stroke patients. However, the potential beneficial effect associated with statins requires further validation using randomized clinical trials.

Analysis of complex human movements can provide valuable insights for movement rehabilitation, sports training, humanoid robot design and control, and human–robot interaction. To accomplish complex movement, the central nervous system must coordinate the musculo-skeletal system to achieve task and internal (e.g., effort minimisation) objectives. This paper proposes an inverse optimal control approach for analysing complex human movement that does not assume that the control objective(s) remains constant throughout the movement. The movement trajectory is assumed to be optimal with respect to a cost function composed of the sum of weighted basis cost functions, which may be time varying. The weights of the cost function are recovered using a sliding window. To illustrate the proposed approach, a dataset consisting of standing broad jump to targets at three different distances is collected. The method can be used to extract control objectives that influence task success, identify different motion strategies/styles, as well as to observe how control strategy changes during the motor learning process. Kinematic analysis confirms that the identified control objectives, including centre-of-mass takeoff vector and foot placement upon landing are important to ensure that a given participant lands on the target. The dataset, including nearly 800 jump trajectories from 22 participants is also provided.

Antidiabetic properties of red yeast rice, bitter gourd, and chromium have gained scientific support. This study aimed to test whether a nutraceutical combination of these 3 materials prevented dedifferentiation of pancreatic β cells. Male db/db mice (8 weeks of age) were allocated into four groups (DB, DB/L, DB/M, and DB/H; n = 8–10) and fed a high‐fat diet containing 0%, 0.2%, 0.4%, or 1% nutraceutical, respectively, whereas wild‐type mice receiving a standard diet served as a healthy control (C; n = 10). The nutraceutical contained 10 mg/g monacolin K, 165 µg/g chromium, and 300 mg/g bitter gourd. After 8‐weeks dietary treatment, diabetic syndromes (including hyperglycemia, hyperphagia, excessive drinking, polyuria, glucosuria, albuminuria, and glucose intolerance), were improved by the nutraceutical in a dose‐dependent fashion. Decreased insulin and increased glucagon in serum and pancreatic islets in db/db mice were abolished in the DB/H group. Furthermore, supplementation curtailed dedifferentiation of β cells, as evidenced by decreasing the dedifferentiation marker (Aldh1a3) and increasing β‐cell‐enriched genes and transcription factors (Ins1, Ins2, FOXO1, and NKX6.1), as well as nuclear localization of NKX6.1 in pancreatic islets when compared to the DB group. We concluded that this nutraceutical, a combination of Monascus purpureus, Momordica charantia, and chromium, could be used as an adjunct for type 2 diabetes treatment and delay disease progression by sustaining β‐cell function., Beta‐cell dedifferentiation is an important issue leads to beta‐cell failure in type 2 diabetes. This study shows an antidiabetic nutraceutical combination of red yeast rice, bitter gourd, and chromium is able to curb beta‐cell dedifferentiation by decreasing the dedifferentiation marker (Aldh1a3) and increasing beta‐cell‐enriched genes (Ins1, Ins2, FOXO1, and NKX6.1), as well as nuclear localization of NKX6.1.

Atherosclerosis is one of the chronic progressive diseases, which is caused by vascular injury and promoted by the interaction of various inflammatory factors and inflammatory cells. In recent years, kruppel-like factor 4 (KLF4), a significant transcription factor that participated in cell growth, differentiation and proliferation, has been proved to cause substantial impacts on regulating cardiovascular disease. This paper will give a comprehensive summary to highlight KLF4 as a crucial regulator of foam cell formation, vascular smooth muscle cells (VSMCs) phenotypic transformation, macrophage polarization, endothelial cells inflammation, lymphocyte differentiation and cell proliferation in the process of atherosclerosis. Recent studies show that KLF4 may be an important "molecular switch" in the process of improving vascular injury and inflammation under harmful stimulation, suggesting that KLF4 is a latent disease biomarker for the therapeutic target of atherosclerosis and vascular disease.

Background Posttranscriptional gene silencing (PTGS) is one of the most important mechanisms for plants during viral infection. However, viruses have also developed viral suppressors to negatively control PTGS by inhibiting microRNA (miRNA) and short-interfering RNA (siRNA) regulation in plants. The first identified viral suppressor, P1/HC-Pro, is a fusion protein that was translated from potyviral RNA. Upon infecting plants, the P1 protein itself is released from HC-Pro by the self-cleaving activity of P1. P1 has an unknown function in enhancing HC-Pro-mediated PTGS suppression. We performed proteomics to identify P1-interacting proteins. We also performed transcriptomics that were generated from Col-0 and various P1/HC-Pro-related transgenic plants to identify novel genes. The results showed several novel genes were identified through the comparative network analysis that might be involved in P1/HC-Pro-mediated PTGS suppression. Results First, we demonstrated that P1 enhances HC-Pro function and that the mechanism might work through P1 binding to VERNALIZATION INDEPENDENCE 3/SUPERKILLER 8 (VIP3/SKI8), a subunit of the exosome, to interfere with the 5′-fragment of the PTGS-cleaved RNA degradation product. Second, the AGO1 was specifically posttranslationally degraded in transgenic Arabidopsis expressing P1/HC-Pro of turnip mosaic virus (TuMV) (P1/HCTu plant). Third, the comparative network highlighted potentially critical genes in PTGS, including miRNA targets, calcium signaling, hormone (JA, ET, and ABA) signaling, and defense response. Conclusion Through these genetic and omics approaches, we revealed an overall perspective to identify many critical genes involved in PTGS. These new findings significantly impact in our understanding of P1/HC-Pro-mediated PTGS suppression.

AimLotus japonicus is a herbaceous perennial legume that has been used extensively as a genetically tractable model system for deciphering the molecular genetics of symbiotic nitrogen fixation. Our aim is to improve the L. japonicus reference genome sequence, which has so far been based on Sanger and Illumina sequencing reads from the L. japonicus accession MG-20 and contained a large fraction of unanchored contigs.Methods and ResultsHere, we use long PacBio reads from L. japonicus Gifu combined with Hi-C data and new high-density genetic maps to generate a high-quality chromosome-scale reference genome assembly for L. japonicus. The assembly comprises 554 megabases of which 549 were assigned to six pseudomolecules that appear complete with telomeric repeats at their extremes and large centromeric regions with low gene density.Conclusion and PerspectivesThe new L. japonicus Gifu reference genome and associated expression data represent valuable resources for legume functional and comparative genomics. Here, we provide a first example by showing that the symbiotic islands recently described in Medicago truncatula do not appear to be conserved in L. japonicus.

Anaerobic cultivation methods of bacteria are indispensable in microbiology. One methodology is to cultivate the microbes in anaerobic enclosure with oxygen-adosrbing chemicals. Here, we report an electronic extension of such strategy for facultative anaerobic bacteria. The technique is based a bioreactor with entire operation including turbidity measurement, fluidic mixing, and gas delivery in an anaerobic enclosure. Wireless data transmission is employed and the anaerobic condition is achieved with gas pack. Although the technique is not meant to completely replace the anaerobic chamber for strict anaerobic bacteria, it provides a convenient way to bypass the cumbersome operation in anaerobic chamber for facultative anaerobic bacteria. Such a cultivation strategy is demonstrated with Escherichia coli with different carbon sources and hydrogen as energy source.

To observe the effect of acupuncture plus hyperbaric oxygen (HBO) on cerebral blood perfusion in patients with delayed encephalopathy after carbon monoxide poisoning (DEACMP).Twenty-eight patients with DEACMP were randomly divided into acupuncture group (After the treatment, the values of f, fD* and BI scores were significantly increased in both acupuncture group and control groups (Acupuncture combined with HBO can significantly improve the low-perfusion of bilate-ral semi-oval center and daily living ability in patients with DEACMP, being significantly superior to simple HBO therapy in the curative effect.

Some candidate genes have been robustly reported to be associated with complex traits, such as the fat mass and obesity-associated (FTO) gene on body mass index (BMI), and the fibroblast growth factor 5 (FGF5) gene on blood pressure levels. It is of interest to know whether an environmental factor (E) can attenuate or exacerbate the adverse influence of a candidate gene. To this end, we here evaluate the performance of "genetic risk score" (GRS) approaches to detect "gene-environment interactions" (G × E). In the first stage, a GRS is calculated according to the genotypes of variants in a candidate gene. In the second stage, we test whether E can significantly modify this GRS effect. This two-stage procedure can not only provide a p-value for a G × E test but also guide inferences on how E modifies the adverse effect of a gene. With systematic simulations, we compared several ways to construct a GRS. If E exacerbates the adverse influence of a gene, GRS formed by the elastic net (ENET) or the least absolute shrinkage and selection operator (LASSO) is recommended. However, the performance of ENET or LASSO will be compromised if E attenuates the adverse influence of a gene, and using the ridge regression (RIDGE) can be more powerful in this situation. Applying RIDGE to 18,424 subjects in the Taiwan Biobank, we showed that performing regular exercise can attenuate the adverse influence of the FTO gene on four obesity measures: BMI (p = 0.0009), body fat percentage (p = 0.0031), waist circumference (p = 0.0052), and hip circumference (p = 0.0001). As another example, we used RIDGE and found the FGF5 gene has a stronger effect on blood pressure in Han Chinese with a higher waist-to-hip ratio [p = 0.0013 for diastolic blood pressure (DBP) and p = 0.0027 for systolic blood pressure (SBP)]. This study provides an evaluation on the GRS approaches, which is important to infer whether E attenuates or exacerbates the adverse influence of a candidate gene.

Atherosclerosis (AS) is the pathophysiologic basis of many cardiovascular diseases. A number of studies have shown that post-translational modification (PTM) contributes to the initiation and progression of AS. For example, recent studies found that SUMOylation, ie, small ubiquitin-like modifier (SUMO) conjugation to target substrate proteins, was involved in AS. This PTM appears related to endothelial cell dysfunction (ECD), dyslipidemia and vascular smooth muscle cell (VSMC) proliferation. This review focuses on the molecular effects of SUMOylation in the initiation and progression of AS, including ECD, dyslipidemia and VSMC proliferation to better understand this pathologic process.

1,5-Diaminonaphthalene functionalized carbon nanodots (DAN-CDs) were explored as a novel matrix for direct detection of small molecules by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) in negative ion mode. By using DAN-CDs as the matrix, we could detect not only biological small molecules such as fatty acids (FAs), amino acids, peptide Gly–Gly and dopamine, but also anticancer drug erlotinib. By comparison with the performance of CDs, DAN, and their binary matrix, DAN-CDs were favored because of their lower matrix background interference and good detection sensitivity. In addition, the DAN-CDs matrix displayed good salt tolerance and was further applied for plasma detection and qualitative detection of endogenous FAs in a plasma sample. Furthermore, the covalent amide bonds in the DAN-CDs matrix reduced signal interference from the matrix. These results demonstrated that DAN-CDs are a novel negative ion mode matrix for the analysis of small molecules in bio-samples by MALDI-MS.

Tomato spotted wilt orthotospovirus (TSWV) causes devastating losses to agronomic and ornamental crops worldwide. Currently, there is no effective strategy to control this disease. Use of biotic inducers to enhance plant resistance to viruses maybe an effective approach. Our previous study indicated that Tagitinin A (Tag A) has a high curative and protective effect against TSWV. However, the underlying molecular mechanism of Tag A-mediated antiviral activity remains unknown. In this study, Tag A reduced the expression of the NSs, NSm genes was very low in untreated leaves following TSWV infection. In addition, the expression of all TSWV genes in the inoculated and systemic leaves was inhibited in the protective assay, and with an inhibition rate of more than 85% in systemic leaves. Tag A increased phenylalanine ammonia-lyase (PAL) activity in the curative and protective assays. The concentrations of jasmonic acid (JA) and jasmonic acid -isoleucine (JA-Ile) and the expression of its key gene NtCOI1 in Tag A-treated and systemic leaves of treated plants were significantly higher than those of the control plant. Furthermore, Tag A-induced resistance to TSWV could be eliminated by VIGS-mediated silencing of the NtCOI1 gene. These indicated that Tag A acts against TSWV by activating the JA defense signaling pathway.

The purpose of this study was to investigate the early risk factors for the exacerbation of coronavirus disease 2019 (COVID-19) pneumonia. Restrospective analysis of clinical data of 85 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including gender, age, comorbidities, symptoms, blood routine, clotting profile, biochemical examination, albumin, myocardial enzyme profile, inflammatory markers, and chest computed tomography (CT). All laboratory examinations were measured within first 24 hours after admission, and chest CT was performed before admission. A total of 56 (65.9%) patients had a history of exposure to the Huanan seafood market in Wuhan. Fever and dry cough accounted for the highest percentage of all symptoms. Male COVID-2019 patients were more likely to develop severe pneumonia. Patients with severe and critical conditions are older and have higher rates of hypertension (P = .003) and coronary heart disease (P = .017). All severe and critical patients infected with SARS-CoV-2 showed bilateral lung involvement and have more multiple lobes involvement than common patients (P < .001). Severe and critical patients showed higher white blood cell count (P = .006), neutrophil (NEU) count (P = .001), NEU% (P = .002), procalcitonin (P = .011), C-reactive protein (P = .003), prothrombin time (P = .035), D-dimer (P = .025), aspartate aminotransferase (P = .006), and lower lymphocyte (LYM) count (P = .019), LYM% (P = .001), albumin (P < .001). Logistic regression analysis showed that NEU count is an independent risk factor for deterioration, with the threshold of 6.5 × 109 ·L-1 . We concluded that the laboratory independent risk factor for the progression of COVID-19 pneumonia is NEU count. In addition, COVID-19 patients with bilateral lung involvement or multiple lobes involvement should be taken seriously and actively treated to prevent deterioration of the disease.

The land process model, ISAM, is extended to accurately simulate contemporary soybean and maize crop yields, and estimate changes in yield over the period 1901–2100 driven by past and future changes in environmental factors – atmospheric CO2 level ([CO2]) and climate (temperature and precipitation) – and management factors – nitrogen fertilizer and deposition, irrigation, and crop harvest areas. Over the 20th century, each of these factors contributes to the increase in global crop yield with increasing nitrogen fertilizer application the strongest of these drivers for maize and increasing [CO2] the strongest for soybean. Over the 21st century, two future scenarios – RCP4.5-SSP2 and RCP8.5-SSP5 – of the environmental and management factors are modeled to estimate their influence on future crop yield. For both crops under both scenarios, changing climate drives yield lower, while rising [CO2] drives yield higher. For soybean, the negative climate effect is more than offset by the other drivers – particularly the increase in [CO2] – leading to an increase in global soybean yield by the 2090s. For maize, combined negative climate and harvest area effects are offset in RCP4.5-SSP2, which has continued growth in nitrogen fertilizer application, leaving global yield roughly unchanged. However, in RCP8.5-SSP5 maize yield declines since this scenario has greater warming of climate and weaker nitrogen fertilizer application than RCP4.5-SSP2. The model also projects differences between geographical regions; notably, higher temperatures in tropical regions limit photosynthesis rates and reduce light interception by accelerating phenological development in both crops, particularly for RCP8.5-SSP5 and for soybean.

The sedimentation rate in the northeastern South China Sea (SCS) is high and it therefore offers an opportunity for a high-resolution paleoceanographic study. This study is based on high-resolution AMS 14C dating on forams and oxygen isotope data of two planktonic foraminifera species (Globigerinoides ruber and Neogloboquadrina dutertrei) from the sediment core, MD18-3568, collected from the northeastern SCS, to reconstruct upper-ocean stratification since 35 ka.The marine sediment core MD18-3568 is located on the accretionary wedge off SW Taiwan at a water depth of 1,315 m, the whole core is dominated by hemipelagic sediments and is of 20.7 m in length. Samples for AMS 14C dating were selected at roughly 2 ka interval with a total of 16 samples. The ages show a continuously younging-upward trend with bottom of this core around 35,000 years BP. Samples for high-resolution oxygen isotope measurements were selected at a nominal 500-year age interval. The difference in δ18O between G. ruber (mixed layer dwelling species) and N. dutertrei (thermocline dwelling species) is used to reconstruct the upper ocean stratification with large difference indicating significant ocean stratification and vice versa. The results show moderate upper ocean stratification during 35-24 ka, and it became less stratified during the Last Glacial Maximum (LGM, 23-19 ka). During the deglacial stage, the stratification gradually became stronger until the early Holocene (12-9 ka), and it has kept strong upper-ocean stratification since 9 ka. Literature has documented less rainfall intensity during the LGM and heavy rainfall during the Holocene in southern Taiwan. We interpret the upper-ocean stratification in the NE South China Sea near Taiwan is linked to the amount of freshwater inputs from Taiwan. Less Taiwan freshwater input during the LGM led to a weak stratified upper ocean and a large amount of freshwater input from Taiwan led to a strong upper-ocean stratification during the Holocene.

The Loshui Sandstone, a Miocene turbidite succession accumulated in the northern slope of the rifted continental margin of the South China Sea, is exposed in the Hengchun Peninsula, Taiwan. We conduct lithofacies analysis to understand the depositional processes and mechanisms of the gigantic-thick turbidite succession.Several features can be recognized from outcrops: (1) the Loshui Sandstone is of around 1,000 m thick with turbidite units stacked vertically; (2) high net-to-gross ratio (> 0.9) with dominant fine-to-medium grained sandstones, amalgamated beds are commonly found in the very thickly-bedded turbidites; (3) thick individual turbidite beds with a nominal thickness of 70 cm, which is thicker than classical Bouma sequence; and (4) limited deep scouring surfaces and thick mud are found. Two end-member lithofacies of high-density turbidites and low-density turbidites, respectively, are identified. High-density turbidites are thicker (more than 1 m thick) and coarser in grain size (mostly medium sands) with abundant massive intervals, dewatering structures and/or climbing ripples. Low-density turbidites tend to be thinner in thickness and finer in grain size (mostly fine sands) with parallel bedding and/or normal ripples. In addition to the above two lithofacies, chaotic deposits of mass transport deposits (MTDs) are also widespread within the studied succession.Sand-rich, vertically aggrading succession, but lack of deep-scouring surfaces and levee deposits, indicates that turbidites are laid down by unconfined turbidity currents in a sand-rich deepwater lobe. In addition, gigantic thick turbidite unit stacked continuously up to 1,000 m, implying that the lobe is confined within a rapidly subsiding basin. We interpreted that the Loshui Sandstone is vertically stacked and accumulated within a fault-bounded trough in the deepwater area of the rifted continental margin of the South China Sea.

Spring wheat is a major food crop that is a staple for a large number of people in India and the world. To address the issue of food security, it is essential to understand how productivity of spring wheat changes with changes in environmental conditions and agricultural management practices. The goal of this study is to quantify the role of different environmental factors and management practices on wheat production in India in recent years (1980 to 2016). Elevated atmospheric CO2 concentration ([CO2]) and climate change are identified as two major factors that represent changes in the environment. The addition of nitrogen fertilizers and irrigation practices are the two land-management factors considered in this study. To study the effects of these factors on wheat growth and production, we developed crop growth processes for spring wheat in India and implemented them in the Integrated Science Assessment Model (ISAM), a state-of-the-art land model. The model is able to capture site-level observed crop leaf area index (LAI) and country scale production. Numerical experiments are conducted with the model to quantify the effect of each factor on wheat production on a country scale for India. Our results show that elevated [CO2] levels, water availability through irrigation and nitrogen fertilizers have led to an increase in annual wheat production at 0.68, 0.24 and 0.31 Mt/yr, respectively, averaged over the time period 1980-2016. However, elevated temperatures have reduced the total wheat production at a rate of 0.37 Mt/yr during the study period. Overall, the [CO2], irrigation, fertilizers, and temperature forcings have led to 39 %, 15 %, 20 % and −16 % changes in countrywide production, respectively. The magnitudes of these factors spatially vary across the country thereby affecting production at regional scales. Results show that favourable growing season temperatures, moderate to high fertilizer application, high availability of irrigation facilities, and moderate water demand make the Indo-Gangetic plain the most productive region while the arid northwest region is the least productive due to high temperatures and lack of irrigation facilities to meet the high water demand.

Purpose Functional MRI has played a fundamental role in Parkinson's disease(PD) study. In this paper, we performed an independent component analysis (ICA) based on functional networks to reveal the intricate variations on the morphology and functional properties of brain. Our analysis aims at discovering the differences between PD patients with sensorimotor function impairment and normal controls(NC), thus helping to understand the coordination neurological function degeneration in PD objectively. Method We investigated the blood oxygen level dependent(BOLD) functional MRI obtained at a 3.0 T MRI scanner. 30 PD patients and 28 NC subjects underwent the scan in resting state. The signals of sensory and motor coordinative control areas in the sensorimotor, insula and cerebellum networks acquired by ICA(Independent Component Analysis)were applied to analyze the functional alterations. Specifically, intra-network analysis was performed with signals in local networks, and inter-network analysis was conducted by functional network connectivity (FNC) with signals across different networks. Two sample T test was carried out to detect the significant (p Conclusion We identified an obvious increase in bilateral posterior insula, but decrease in bilateral cerebellum hemisphere, supplementary motor area(SMA) and precentral gyrus paracentral lobule of left postcentral gyrus. Besides, we found a significantly increased connection between independent component (IC) 13 which was located in right postcentral gyrus and cerebellum. Decreased connections were detected between sensory and motor cortex in sensorimotor network and between cerebellum and insula network by FNC analysis in PD patients as well. Discussion Parkinson's disease derives from the degeneration of the dopaminergic neurons in substantia nigra, and results in decreased secretion of inhibitory neurotransmitter. The significant differences between PD and NC groups in our research maybe explain the clinical manifestations of prominent bradykinesia and multiple extrapyramidal symptoms.