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Intermittent hypoxia (IH) is a hallmark manifestation of obstructive sleep apnea (OSA), a widespread disorder of breathing. This Review focuses on the role of hypoxia-inducible factors (HIFs) in hypertension, type 2 diabetes (T2D), and cognitive decline in experimental models of IH patterned after O2 profiles seen in OSA. IH increases HIF-1α and decreases HIF-2α protein levels. Dysregulated HIFs increase reactive oxygen species (ROS) through HIF-1-dependent activation of pro-oxidant enzyme genes in addition to reduced transcription of antioxidant genes by HIF-2. ROS in turn activate chemoreflex and suppress baroreflex, thereby stimulating the sympathetic nervous system and causing hypertension. We also discuss how increased ROS generation by HIF-1 contributes to IH-induced insulin resistance and T2D as well as disrupted NMDA receptor signaling in the hippocampus, resulting in cognitive decline.

Radiocesium remediation is desirable for ecological protection, human health and sustainable development of nuclear energy. Effective capture of Cs + from acidic solutions is still challenging, mainly due to the low stability of the adsorbing materials and the competitive adsorption of protons. Herein, the rapid and highly selective capture of Cs + from strongly acidic solutions is achieved by a robust K + -directed layered metal sulfide KInSnS 4 (InSnS-1) that exhibits excellent acid and radiation resistance. InSnS-1 possesses high adsorption capacity for Cs + and can serve as the stationary phase in ion exchange columns to effectively remove Cs + from neutral and acidic solutions. The adsorption of Cs + and H 3 O + is monitored by single-crystal structure analysis, and thus the underlying mechanism of selective Cs + capture from acidic solutions is elucidated at the molecular level. The removal of radiocesium from acidic solutions is challenging. Here, the authors report the rapid and highly selective capture of cesium(I) from strongly acidic solutions by a robust layered metal sulfide.

Curcumin is a natural compound with great potential for disease treatment. A large number of studies have proved that curcumin has a variety of biological activities, among which anti-inflammatory effect is a significant feature of it. Inflammation is a complex and pervasive physiological and pathological process. The physiological and pathological mechanisms of inflammatory bowel disease, psoriasis, atherosclerosis, COVID-19 and other research focus diseases are not clear yet, and they are considered to be related to inflammation. The anti-inflammatory effect of curcumin can effectively improve the symptoms of these diseases and is expected to be a candidate drug for the treatment of related diseases. This paper mainly reviews the anti-inflammatory effect of curcumin, the inflammatory pathological mechanism of related diseases, the regulatory effect of curcumin on these, and the latest research results on the improvement of curcumin pharmacokinetics. It is beneficial to the further study of curcumin and provides new ideas and insights for the development of curcumin anti-inflammatory preparations.

Background To tackle the issue with the low usage of primary healthcare service in China, it is essential to align resource distribution with the preferences of the community residents. There are few academic researches for describing residents’ perceived characteristics of healthcare services in China. This study aims to investigate the preferences of healthcare services utilization in community residents and explore the heterogeneity. The findings will be useful for the policy makers to take targeted measures to tailor the provision of healthcare services. Methods The face-to-face interviews and surveys were conducted to elicit four key attributes (care provider; mode of services; cost; travel time) of the preference from community residents for healthcare utilization. A rational test was presented first to confirm the consistency, and then 16 pairs of choice tasks with 12 sociodemographic items were given to the respondents. Two hypothetical options for each set, without an opt-out option, were presented in each choice task. The latent class analysis (LCA) was used to analyse the data. Results Two thousand one hundred sixty respondents from 36 communities in 6 cities were recruited for our study. 2019 (93.47%) respondents completed valid discrete choice experiment (DCE) questionnaires. The LCA results suggested that four groups of similar preferences were identified. The first group (27.29%) labelled as “Comprehensive consideration” had an even preference of all four attributes. The second group (37.79%) labelled as “Price-driven” preferred low-price healthcare services. The third group labelled as “Near distance” showed a clear preference for seeking healthcare services nearby. The fourth group (34.18%) labelled as “Quality seeker” preferred the healthcare service provided by experts. Willingness to pay (WTP) results showed that people were willing to accept CNY202.12($29.37) for Traditional Chinese Medicine (TCM) services and willing to pay CNY604.31($87.81) for the service provided by experts. Conclusions Our study qualitatively measures the distinct preferences for healthcare utilization in community residents in China. The results suggest that the care provider, mode of services, travel time and cost should be considered in priority setting decisions. The study, however, reveals substantial disagreement in opinion of TCM between different population subgroups.

The impact of missing data on quantitative research can be serious, leading to biased estimates of parameters, loss of information, decreased statistical power, increased standard errors, and weakened generalizability of findings. In this paper, we discussed and demonstrated three principled missing data methods: multiple imputation, full information maximum likelihood, and expectation-maximization algorithm, applied to a real-world data set. Results were contrasted with those obtained from the complete data set and from the listwise deletion method. The relative merits of each method are noted, along with common features they share. The paper concludes with an emphasis on the importance of statistical assumptions, and recommendations for researchers. Quality of research will be enhanced if (a) researchers explicitly acknowledge missing data problems and the conditions under which they occurred, (b) principled methods are employed to handle missing data, and (c) the appropriate treatment of missing data is incorporated into review standards of manuscripts submitted for publication.

Epstein-Barr virus (EBV) is associated with a range of epithelial and B cell malignancies as well as autoimmune disorders, for which there are still no specific treatments or effective vaccines. Here, we isolate EBV gH/gL-specific antibodies from an EBV-infected individual. One antibody, 1D8, efficiently neutralizes EBV infection of two major target cell types, B cells and epithelial cells. In humanized mice, 1D8 provides protection against a high-dose EBV challenge by substantially reducing viral loads and associated tumor burden. Crystal structure analysis reveals that 1D8 binds to a key vulnerable interface between the D-I/D-II domains of the viral gH/gL protein, especially the D-II of the gH, thereby interfering with the gH/gL-mediated membrane fusion and binding to target cells. Overall, we identify a potent and protective neutralizing antibody capable of reducing the EBV load. The novel vulnerable site represents an attractive target that is potentially important for antibody and vaccine intervention against EBV infection. Currently, there are no treatments or vaccines against Epstein-Barr virus (EBV) infection. Here, Zhu et al. isolate gH/gL-specific antibodies from infected donors and identify 1D8, that substantially reduces infection levels in both, B- and epithelial cells, and reduces tumor burdens in EBV-challanged humanized mice due to interferance with the gH/gL-mediated membrane fusion and binding.

Background Nod-like receptor protein 3 (NLRP3) inflammasome is a crucial factor in mediating inflammatory responses after cerebral ischemia/reperfusion (I/R), but the cellular location of NLRP3 inflammasome in cerebral I/R has yet come to a conclusion, and there is still no specific evidence to state the relationship between mitochondria and the NLRP3 inflammasome in cerebral I/R. Methods In the present study, we detected the cellular localization of NLRP3 inflammasomes in a transient middle cerebral artery occlusion (tMCAO) rat model and a transwell co-culture cell system under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. Then, we investigated the relationship between mitochondrial dysfunction and the activation of NLRP3 inflammasomes in different cell types after OGD/R and cerebral I/R injury. Results Our results showed that NLRP3 inflammasomes were first activated in microglia soon after cerebral I/R injury onset and then were expressed in neurons and microvascular endothelial cells later, but they were mainly in neurons. Furthermore, mitochondrial dysfunction played an important role in activating NLRP3 inflammasomes in microglia after OGD/R, and mitochondrial protector could inhibit the activation of NLRP3 inflammasomes in cerebral I/R rats. Conclusion Our findings may provide novel insights into the cell type-dependent activation of NLRP3 inflammasomes at different stages of cerebral I/R injury and the role of mitochondrial dysfunction in activating the NLRP3 inflammasome pathway.

As an important platform molecule, atropisomeric QUINOL plays a crucial role in the development of chiral ligands and catalysts in asymmetric catalysis. However, efficient approaches towards QUINOL remain scarce, and the resulting high production costs greatly impede the related academic research as well as downstream industrial applications. Here we report a direct oxidative cross-coupling reaction between isoquinolines and 2-naphthols, providing a straightforward and scalable route to acquire the privileged QUINOL scaffolds in a metal-free manner. Moreover, a NHC-catalyzed kinetic resolution of QUINOL N-oxides with high selectivity factor is established to access two types of promising axially chiral Lewis base catalysts in optically pure forms. The utility of this methodology is further illustrated by facile transformations of the products into QUINAP, an iconic ligand in asymmetric catalysis. 1-(Isoquinolin-1-yl)naphthalen-2-ol (QUINOL) is an atropisomeric heterobiaryl that serves as a platform for the synthesis of other biaryl ligands useful in asymmetric catalysis. Here, the authors report a straightforward oxidative cross-coupling reaction between isoquinolines and 2-naphthols to efficiently access the QUINOL scaffolds in a metal-free manner.

Soil salinity is a main abiotic stress in agriculture worldwide. The Na+/H+ antiporters (NHXs) play pivotal roles in intracellular Na+ excretion and vacuolar Na+ compartmentalization, which are important for plant salt stress resistance (SSR). However, few systematic analyses of NHXs has been reported in allotetraploid rapeseed so far. Here, a total of 18 full-length NHX homologs, representing seven subgroups (NHX1-NHX8 without NHX5), were identified in the rapeseed genome (AnAnCnCn). Number variations of BnaNHXs might indicate their significantly differential roles in the regulation of rapeseed SSR. BnaNHXs were phylogenetically divided into three evolutionary clades, and the members in the same subgroups had similar physiochemical characteristics, gene/protein structures, and conserved Na+ transport motifs. Darwin´s evolutionary pressure analysis suggested that BnaNHXs suffered from strong purifying selection. The cis-element analysis revealed the differential transcriptional regulation of NHXs between the model Arabidopsis and B. napus. Differential expression of BnaNHXs under salt stress, different nitrogen forms (ammonium and nitrate), and low phosphate indicated their potential involvement in the regulation of rapeseed SSR. Global landscapes of BnaNHXs will give an integrated understanding of their family evolution and molecular features, which will provide elite gene resources for the genetic improvement of plant SSR through regulating the NHX-mediated Na+ transport.

Background Plants worldwide are often stressed by low Fe availability around the world, especially in aerobic soils. Therefore, the plant growth, seed yield, and quality of crop species are severely inhibited under Fe deficiency. Fe metabolism in plants is controlled by a series of complex transport, storage, and regulatory mechanisms in cells. Allohexaploid wheat ( Triticum aestivum L.) is a staple upland crop species that is highly sensitive to low Fe stresses. Although some studies have been previously conducted on the responses of wheat plants to Fe deficiency, the key mechanisms underlying adaptive responses are still unclear in wheat due to its large and complex genome. Results Transmission electron microscopy showed that the chloroplast structure was severely damaged under Fe deficiency. Paraffin sectioning revealed that the division rates of meristematic cells were reduced, and the sizes of elongated cells were diminished. ICP-MS-assisted ionmics analysis showed that low-Fe stress significantly limited the absorption of nutrients, including N, P, K, Ca, Mg, Fe, Mn, Cu, Zn, and B nutrients. High-throughput transcriptome sequencing identified 378 and 2,619 genome-wide differentially expressed genes (DEGs) were identified in the shoots and roots between high-Fe and low-Fe conditions, respectively. These DEGs were mainly involved in the Fe chelator biosynthesis, ion transport, photosynthesis, amino acid metabolism, and protein synthesis. Gene coexpression network diagrams indicated that TaIRT1b-4A , TaNAS2-6D , TaNAS1a-6A , TaNAS1-6B, and TaNAAT1b-1D might function as key regulators in the adaptive responses of wheat plants to Fe deficiency. Conclusions These results might help us fully understand the morpho-physiological and molecular responses of wheat plants to low-Fe stress, and provide elite genetic resources for the genetic modification of efficient Fe use.