O-Linked β-N-acetylglucosamine (O-GlcNAc) is a carbohydrate post-translational modification on hydroxyl groups of serine and/or threonine residues of cytosolic and nuclear proteins. Analogous to ...phosphorylation, O-GlcNAcylation plays crucial regulatory roles in cellular signaling. Recent work indicates that increased O-GlcNAcylation is a general feature of cancer and contributes to transformed phenotypes. In this minireview, we discuss how hyper-O-GlcNAcylation may be linked to various hallmarks of cancer, including cancer cell proliferation, survival, invasion, and metastasis; energy metabolism; and epigenetics. We also discuss potential therapeutic modulation of O-GlcNAc levels in cancer treatment.
A thermodynamic map showing the solubility and solution properties of polymers in water: The enthalpy and entropy of mixing depend on the interactions in the polymer-water mixture. With the guidance ...of the map, the thermoresponsive properties of a polymer can be predicted before synthesis and its critical solution transition temperature Tc can be obtained from the slope of the straight line that passes through the original point and its location in the quadrant.
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Temperature variations may induce changes in solution properties for thermoresponsive polymers, which have drawn much research attention due to their potential applications in different areas. To meet the practical requirements, rational design of the polymers is important and necessary. We reviewed literature in this field and proposed a thermodynamic map to guide the design of such polymers. The map is drawn up based on the enthalpic and entropic contributions (ΔHm and ΔSm) to the free energy change of mixing (ΔGm). The map is divided into four zones: soluble, insoluble, upper critical solution temperature (UCST), and lower critical solution temperature (LCST), with two lines representing the freezing and boiling points of the solvent (water) as two boundaries for the UCST and LCST zones. With the help of such a map, we attempt to illustrate how the UCST and LCST are affected by the various interactions in polymer-water mixtures, such as hydrophobic and ionic interactions, and hydrogen bonding, so that the thermoresponsive properties of a polymer can be predicted according to their molecular structures. The critical temperatures UCST and/or LCST of a polymer can be obtained from the slope of the straight line that passes through the original point and the location of the polymer on the map. Examples in the literature are shown to fit in different zones of this map, and we also demonstrate how the variations of the chemical composition or the molecular structure of the polymers can change the intra- and inter-molecular interactions involved, which in turn change the solution properties of the polymers and induce changes in the critical solution temperatures. This map may be used in the design and preparation of thermoresponsive polymers with UCST and LCST on demand.
Coronavirus disease 2019 (COVID-19) is a new pandemic that the entire world is facing since December of 2019. Increasing evidence has shown that metformin is linked to favorable outcomes in patients ...with COVID-19. The aim of this study was to address whether outpatient or inpatient metformin therapy for type 2 diabetes mellitus is associated with low in-hospital mortality in patients hospitalized for COVID-19.
We searched studies published in PubMed, Embase, Google Scholar and Cochrane Library up to November 1, 2022. Raw event data extracted from individual study were pooled using the Mantel-Haenszel approach. Odds ratio (OR) or hazard ratio (HR) adjusted for covariates that potentially confound the association using multivariable regression or propensity score matching was pooled by the inverse-variance method. Random effect models were applied for meta-analysis due to variance among studies.
Twenty-two retrospective observational studies were selected. The pooled unadjusted OR for outpatient metformin therapy and in-hospital mortality was 0.48 (95% CI, 0.37-0.62) and the pooled OR adjusted with multivariable regression or propensity score matching was 0.71 (95% CI, 0.50-0.99). The pooled unadjusted OR for inpatient metformin therapy and in-hospital mortality was 0.18 (95% CI, 0.10-0.31), whereas the pooled adjusted HR was 1.10 (95% CI, 0.38-3.15).
Our results suggest that there is a significant association between the reduction of in-hospital mortality and outpatient metformin therapy for type 2 diabetes mellitus in patients hospitalized for COVID-19.
Anthropogenic climate change has emerged as a critical environmental problem, prompting frequent investigations into its consequences for various ecological systems. Few studies, however, have ...explored the effect of climate change on ecological stability and the underlying mechanisms. We conduct a field experiment to assess the influence of warming and altered precipitation on the temporal stability of plant community biomass in an alpine grassland located on the Tibetan Plateau. We find that whereas precipitation alteration does not influence biomass temporal stability, warming lowers stability through reducing the degree of species asynchrony. Importantly, biomass temporal stability is not influenced by plant species diversity, but is largely determined by the temporal stability of dominant species and asynchronous population dynamics among the coexisting species. Our findings suggest that ongoing and future climate change may alter stability properties of ecological communities, potentially hindering their ability to provide ecosystem services for humanity.
Abstract
On 2022 July 13, NASA released to the whole world the data obtained by the James Webb Space Telescope (JWST) Early Release Observations (ERO). These are the first set of science-grade data ...from this long-awaited facility, marking the beginning of a new era in astronomy. In the study of the early universe, JWST will allow us to push far beyond
z
≈ 11, the redshift boundary previously imposed by the 1.7
μ
m red cutoff of the Hubble Space Telescope (HST). In contrast, JWST’s NIRCam reaches ∼5
μ
m. Among the JWST ERO targets there is a nearby galaxy cluster SMACS 0723-73, which is a massive cluster and has been long recognized as a potential “cosmic telescope” in amplifying background galaxies. The ERO six-band NIRCam observations on this target have covered an additional flanking field not boosted by gravitational lensing, which also sees far beyond HST. Here we report the result from our search of candidate objects at
z
> 11 using these ERO data. In total, there are 87 such objects identified by using the standard “dropout” technique. These objects are all detected in multiple bands and therefore cannot be spurious. For most of them, their multiband colors are inconsistent with known types of contaminants. If the detected dropout signature is interpreted as the expected Lyman break, it implies that these objects are at
z
≈ 11–20. The large number of such candidate objects at such high redshifts is not expected from the previously favored predictions and demands further investigations. JWST spectroscopy on such objects will be critical.
Asymmetric porous ceramic membranes typically have a very thin top layer with finer pores covered on thick porous layers with micrometer‐scale pores. In this study, triple‐layer asymmetric MgAl2O4 ...filtration membranes composed of (i) an Al2O3 support layer (circular pellet with ~10 µm pores) prepared by dry pressing, (ii) a reactively sintered MgAl2O4 intermediate layer (~40 µm in thickness), prepared by dip‐coating with tackifier (PEG‐20000), and (iii) another reactively sintered finer MgAl2O4 membrane layer (~20 µm in thickness), prepared by dip‐coating without tackifier. Different from our previous studies for the microfiltration of submicrometer‐sized particles, in this study we have challenged the ultrafiltration of water‐soluble polymer molecules. Their filtration performance was investigated by removing 1 million molecular‐weight polyethylene oxide (PEO) from water. The rejection rate of the triple‐layer asymmetric filtration membrane to PEO was ~14%. The all‐ceramic membrane in this study showed a comparable rejection rate with the reported inorganic–organic membrane, and it must be promising for excellent chemical and thermal stabilities as well as long durability.
To discover the distribution and risk of pesticides in Jiulong River and estuary, the residues of 102 pesticides were analyzed in water, sediment and clam samples collected from 35 sites in different ...seasons. A total number of 82 pesticides were detected and the occurrence and the risk to human and fish were assessed. Most of pesticides with high frequency were medium or low toxic except for DDTs. DDTs were the significant contaminant and the widely used dicofol was the new source of DDTs. The spatial and seasonal variation of pesticide distribution was linked with the distribution of orchards and farmlands. Health risk from river water consumption was low (RQ < 0.1) while that from clam consumption was medium (RQ = 0.84). Pesticides in water posed great risk to fish and among the 76 water samples analyzed, 65 of them showed high risk (RQ > 1) and 6 showed medium risk (0.1 ≤ QR < 1). The single chemical posed high risk to fish included DDTs, triazophos, fenvalerate, bifenthrin and cyfluthrin, and those showed medium risk included dicofol, butachlor, isocarbophos, terbufos and cyhalothrin. There were 14 single pesticides detected with concentration above 100 ng L−1 in this study and the pesticide with the highest concentration was procymidone (3904 ng L−1). Further experiments illustrated that procymidone could disrupt the expression of vitellogenin in the estuarine fish even at environmental concentrations. DDTs, dicofol, triazophos, isocarbophos, terbufos, cyfluthrin, bifenthrin, fenvalerate, cyhalothrin, butachlor and procymidone have become the significant pesticides and should be considered in aquatic ecosystem risk management.
•Distribution of 82 pesticides in Jiulong River and estuary were analyzed and the risks were assessed.•Moderately or low toxic pesticides made up the main portion of residues except DDTs.•DDTs in clam posed main health risks to consumers and pesticides in water posed high risk to fish.•At least 24 detected pesticides were EDCs and EDC effects of procymidone on local fish were observed.•The pesticides with high eco-risk included DDTs, triazophos, fenvalerate, bifenthrin and cyfluthrin.
Warfarin dosing remains challenging due to narrow therapeutic index and highly individual variability. Incorrect warfarin dosing is associated with devastating adverse events. Remarkable efforts have ...been made to develop the machine learning based warfarin dosing algorithms incorporating clinical factors and genetic variants such as polymorphisms in CYP2C9 and VKORC1. The most widely validated pharmacogenetic algorithm is the IWPC algorithm based on multivariate linear regression (MLR). However, with only a single algorithm, the prediction performance may reach an upper limit even with optimal parameters. Here, we present novel algorithms using stacked generalization frameworks to estimate the warfarin dose, within which different types of machine learning algorithms function together through a meta-machine learning model to maximize the prediction accuracy. Compared to the IWPC-derived MLR algorithm, Stack 1 and 2 based on stacked generalization frameworks performed significantly better overall. Subgroup analysis revealed that the mean of the percentage of patients whose predicted dose of warfarin within 20% of the actual stable therapeutic dose (mean percentage within 20%) for Stack 1 was improved by 12.7% (from 42.47% to 47.86%) in Asians and by 13.5% (from 22.08% to 25.05%) in the low-dose group compared to that for MLR, respectively. These data suggest that our algorithms would especially benefit patients requiring low warfarin maintenance dose, as subtle changes in warfarin dose could lead to adverse clinical events (thrombosis or bleeding) in patients with low dose. Our study offers novel pharmacogenetic algorithms for clinical trials and practice.
Tripteryguim wilfordii Hook (TWH) has significant anti-inflammatory and immunosuppressive properties and is widely used for treating autoimmune and inflammatory diseases. However, the multi-target ...mechanism of TWH on ankylosing spondylitis (AS) remains to be elucidated.
Active components and their target proteins were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Meanwhile, AS-related targets were obtained from the Genecards Database. After overlapping, the targets of TWH against AS were collected. Then protein-protein interaction (PPI) network and core targets analysis were conducted through STRING network platform and Cytoscape software. Moreover, molecular docking methods were utilized to confirm the high affinity between TWH and targets. Finally, DAVID online tool was used to perform gene ontology (GO) and Kyoto encyclopaedia of genes and genome (KEGG) pathway enrichment analysis of overlapping targets.
The TCMSP Database results showed that there were11 active components of TWH against AS. PPI network and core targets analysis suggested that ESR1, VEGF, ICAM-1, and RELA were key targets against AS. Moreover, molecular docking methods confirmed the high affinity between bioactive molecular of TWH and their targets in AS. At last, enrichment analysis indicated that TWH participates in various biological processes, such as cell-cell adhesion, regulation of cell-matrix adhesion, acute inflammatory response, via TNF-α, NF-κB and so forth signalling pathways.
Verified by network pharmacology approach based on data mining and molecular docking methods, multi-target drug TWH may serve as a promising therapeutic candidate for AS but still needs further in vivo/in vitro experiments.
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