Data_Sheet_1_The Vacuolar Molybdate Transporter OsMOT1;2 Controls Molybdenum Remobilization in Rice.PDF

Molybdenum (Mo) is an essential micronutrient for almost all living organisms. The Mo uptake process in plants has been well investigated. However, the mechanisms controlling Mo translocation and remobilization among different plant tissues are largely unknown, especially the allocation of Mo to rice grains that are the major dietary source of Mo for humans. In this study, we characterized the functions of a molybdate transporter, OsMOT1;2, in the interorgan allocation of Mo in rice. Heterologous expression in yeast established the molybdate transport activity of OsMOT1;2. OsMOT1;2 was highly expressed in the blades of the flag leaf and the second leaf during the grain filling stage. Subcellular localization revealed that OsMOT1;2 localizes to the tonoplast. Knockout of OsMOT1;2 led to more Mo accumulation in roots and less Mo translocation to shoots at the seedling stage and to grains at the maturity stage. The remobilization of Mo from older leaves to young leaves under molybdate-depleted condition was also decreased in the osmot1;2 knockout mutant. In contrast, overexpression of OsMOT1;2 enhanced the translocation of Mo from roots to shoots at the seedling stage. The remobilization of Mo from upper leaves to grains was also enhanced in the overexpression lines during grain filling. Our results suggest that OsMOT1;2 may function as a vacuolar molybdate exporter facilitating the efflux of Mo from the vacuole into the cytoplasm, and thus, it plays an important role in the root-to-shoot translocation of Mo and the remobilization of Mo from leaves to grains.</p

Controlled Recognition and Corona Formation by Cascade Micellar Nanoprobes: for Boosting Glioma Theranostics

Both tumor-cell-targeting and BBB (blood-brain barrier)-penetrating ability are the key characteristics for glioma theranostics. We established one type of nanomicellar probe functionalized with a newly developed peptide WES. The micellar system could enact a series of cascaded functions in living bodies. It could specifically recruit the ApoE corona in blood circulation rather than perform nonspecific protein absorption. Following, it could penetrate into the BBB in an active manner. Finally, and most importantly, it could recognize and target the tumor marker as well as deliver drugs effectively toward glioma. The cascaded micellar system has shown satisfactory therapeutic ability for glioma in both a subcutaneous and orthotopic model, which provides a prospective strategy for brain cancer treatment

Photophosphatidylserine Guides Natural Killer Cell Photoimmunotherapy <i>via</i> Tim‑3

Natural killer (NK) cells, in addition to their cytotoxicity function, harbor prominent cytokine production capabilities and contribute to regulating autoimmune responses. T-cell immunoglobulin and mucin domain containing protein-3 (Tim-3) is one of the inhibitory receptors on NK cells and a promising immune checkpoint target. We recently found that phosphatidylserine (PS) binding to Tim-3 can suppress NK cell activation. Therefore, based on the therapeutic potential of Tim-3 in NK-cell-mediated diseases, we developed a photoswitchable ligand of Tim-3, termed photophosphatidylserine (phoPS), that mimics the effects of PS. Upon 365 or 455 nm light irradiation, the isomer of phoPS cyclically conversed the cis/trans configuration, resulting in an active/inactive Tim-3 ligand, thus modulating the function of NK cells in vitro and in vivo. We also demonstrated that reversible phoPS enabled optical control of acute hepatitis. Together, phoPS may be an appealing tool for autoimmune diseases and cytokine storms in the future

A “Cell Space Station” for Spatiotemporal Molecular Manipulation of Immune Checkpoint

Spatiotemporal manipulation of protein distributions, abundances, and functions based on molecular level remains a significant challenge in studying biological systems and developing therapeutics. Particularly, such a nanotherapeutic platform though both specific and internal way is extremely lacking. Herein, we put forward a click chemistry-driven protein sorting (PROCLISORT) strategy, which acted in a cell space station (CSS) to achieve the sequential regulation of specific protein along the entire PD-1 immune checkpoint axis. From the spatial dimension, CSS could achieve comprehensive recognition, anchoring and blocking PD-L1/PD-L2 as well as transport PD-L1 among organelles at the subcellular level. From the time dimension, through the booting control via click reaction, the occurrence of these biological regulatory events became controllable and sequential, thus resulting in rapid and durable down-regulation of PD-L1. Through these smart tasks, this CSS stimulated a satisfactory tumor-immune-therapy effect both in vitro and in vivo. With a rational design, this multistage booting nanoplatform holds promise for molecular manipulation along the disease-related pathway in various living systems

Image_1_Clinical Characteristics, Outcomes, and Risk Factors of Disease Severity in Patients With COVID-19 and With a History of Cerebrovascular Disease in Wuhan, China: A Retrospective Study.pdf

Background and Purpose: Coronavirus disease 2019 (COVID-19) rapidly resulted in a pandemic. Information on patients with a history of cerebrovascular disease (CVD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is limited. This study investigated the clinical features and the risk factors of developing adverse outcomes in patients with COVID-19 and with previous CVD.Methods: This was a single-center retrospective clinical study including all the confirmed cases of COVID-19 at Wuhan Huoshenshan Hospital from February 4 to April 7, 2020. Differences in clinical characteristics were compared between patients with and without a history of CVD. The incidences of severe events comprising all-cause death, intensive care unit admission, shock, and mechanical ventilation usage during hospitalization in two groups were compared using propensity score matching analysis and multivariate logistic regression analyses. Besides, the risk factors of developing severe events in patients with COVID-19 who also have history of CVD were analyzed.Results: A total of 2,554 consecutive patients were included in our study, of whom 109 (4.27%) had a medical history of CVD. Patients with CVD tend to be older and with more comorbidities, including hypertension, diabetes, coronary heart disease, and chronic obstructive pulmonary disease. The levels of white blood cell, neutrophil, C-reactive protein, creatine kinase isoenzymes, and lactate dehydrogenase were higher, whereas the levels of lymphocyte and albumin were lower in the CVD group. Compared to those without CVD, patients with CVD were more likely to have severe events after age matching (12.8 vs. 5.7%, P = 0.012). After adjusting for the confounding effects of age, sex, smoking, and comorbidities, the odds ratio for developing severe events with a history of CVD was 2.326 (95% CI, 1.168–4.630; P = 0.016). Besides, patients with CVD, either with decreased lymphocyte count (OR 9.192, 95% CI, 1.410–59.902, P = 0.020) or increased blood urea nitrogen (OR 5.916, 95% CI, 1.072–32.641, P = 0.041), had a higher risk of developing severe events during hospitalization.Conclusions: Patients with CVD history tend to have adverse clinical outcomes after being infected with SARS-COV-2. Decreased lymphocyte counts and increased blood urea nitrogen levels may be risk factors for adverse outcomes in patients with COVID-19, and had CVD.</p

Additional file 6 of Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

Additional file 6. Study protocol and amendment records

Additional file 2 of Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

Additional file 2: Table S2. NGS panels and number of samples being tested

Additional file 1 of Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

Additional file 1: Table S1. List of associated clinical trials in the study

Nickel and Sulfur Coconfined Nitrogen-Rich Carbon Nanofibers as Anode Materials for Pseudocapacitive Sodium Storage

For sodium-ion batteries (SIBs), carbon materials have generated significant interest based on their rich reserves, low cost, green credentials, and excellent performance as anode materials. However, both capacity value and efficiency are far below expectations as the relatively large ion radius of Na+. In this work, 1D nickel and sulfur coconfined nitrogen-rich carbon materials (S–Ni–NC) are synthesized through electrospinning and vapor sulfuration. The formation of nickel sulfide (NiS) is beneficial for enhancing the specific capacity of sodium-ion batteries due to pseudocapacitive charge storage processes. Forming C–S–C covalent bonds efficiently exposes more active sites, increasing the electrical conductivity and reducing the ion transfer resistance. Thus, the S–Ni–NC electrode displays favorable sodium storage performance, which includes outstanding capacity value (320 mAh g–1 at 0.1 A g–1), rate capability (169.6 mAh g–1 at 5 A g–1), and superior long-cycle property (172.1 mAh g–1 over 1000 cycles at 2 A g–1)

Additional file 4 of Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer

Additional file 4: Figure S1. Stratified analysis in patients with different histologies who carried alterations with different actionability levels. A. Subgroup of lung adenocarcinoma: PFS and OS in patients carrying level 1-2 alterations treated with a matched therapy and a nonmatched therapy. B. Subgroup of lung adenocarcinoma: PFS and OS in patients carrying level 3-4 alterations treated with a matched therapy and a nonmatched therapy. C. Subgroup of other NSCLC histologies: PFS and OS in patients carrying level 1-2 alterations treated with a matched therapy and a nonmatched therapy. D. Subgroup of other NSCLC histologies: PFS and OS in patients carrying level 3-4 alterations treated with a matched therapy and a nonmatched therapy