A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766, exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.People with multiple sclerosis (MS) can experience problems in interpreting others’ emotions from faces or voices. However, to date little is known about whether difficulties in emotion perception in MS are related to broader aspects of social functioning. Also, there are few studies reporting the effect of MS on more ecologically valid assessments of emotion perception using multimodal videos. The current study looks at (1) the effect of MS on perceiving emotions from faces, voices and multimodal videos; (2) the possible role of slowed processing and executive dysfunction in emotion perception problems in MS and (3) the relationship between emotion perception and broader social functioning in MS. 53 people with MS and 31 healthy controls completed tasks of emotion perception and cognition, and assessed their levels of social support and social participation. Participants with MS performed worse than demographically matched controls on all measures of emotion perception. Emotion perception performance was related to cognitive measures in those with MS. Also, significant associations were found between emotion perception difficulties in MS and poorer social function. In particular, people with MS who had poorer emotion perception also reported lower levels of social support from their friends, and regression analysis showed that this prediction was maintained even when disease severity and cognitive function were taken into account. These results show that problems with emotion perception in MS extend to more realistic tasks and may predict key aspects of social functioning.Up to now, the silicon-graphite anode materials with commercial prospect for lithium batteries (LIBs) still face three dilemmas of the huge volume effect, the poor interface compatibility, and the high resistance. To address the above challenges, micro-nano structured composites of graphite coating by ZnO-incorporated and carbon-coated silicon (marked as Gr@ZnO-Si-C) are reasonably synthesized via an efficient and convenient method of liquid phase self-assembly synthesis combined with annealing treatment. The designed composites of Gr@ZnO-Si-C deliver excellent lithium battery performance with good rate performance and stable long-cycling life of 1000 cycles with reversible capacities of 1150 and 780 mAh g-1 tested at 600 and 1200 mA g-1 , respectively. The obtained results reveal that the incorporated ZnO effectively improve the interface compatibility between electrolyte and active materials, and boost the formation of compact and stable surface solid electrolyte interphase layer for electrodes. Furthermore, the pyrolytic carbon layer formed from polyacrylamide can directly improve electrical conductivity, decrease polarization, and thus promote their electrochemical performance. Finally, based on the scalable preparation of Gr@ZnO-Si-C composites, the pouch full cells of Gr@ZnO-Si-C||NCM523 are assembled and used to evaluate the commercial prospects of Si-graphite composites, offering highly useful information for researchers working in the battery industry.Converting carbon dioxide (CO2 ) into high-value fuels or chemicals is considered as a promising way to utilize CO2 and alleviate the excessive greenhouse gas emission. Among multiple catalysis approaches, electrochemical reduction of CO2 to ethanol has an important prospect due to the high energy density and widely applications of ethanol. In recent years, many electrocatalysts for CO2 reduce reaction (CO2 RR) have shown promising catalytic activity for ethanol production. In this review, we will introduce the recent progress in this field. The basic principles and electrochemical performances of CO2 RR are reviewed at first. Then, several categories of active electrocatalysts for CO2 RR to ethanol are summarized, including the discussion of reaction mechanism and catalytic sites. Finally, several possible strategies are proposed, providing guidance for future design and preparation of high-performance catalysts.

Whether and how iron deficiency (ID) impacts patients with heart failure (HF) with preserved ejection fraction (HFpEF) remain unclear. The aim of our study was to investigate the impact of ID on functional status, exercise capacity, and prognosis in HFpEF.

The study population consisted of 300 HFpEF patients. ID was defined as serum ferritin <100μg/L or 100-300μg/L and transferrin-saturation <20%. 3-Deazaadenosine chemical structure Baseline functional status, quality of life (HADS score and EQ 5D index), 6min walking test, echocardiography, and outcome (all-cause mortality and combined all cause-mortality and HF hospitalization) were evaluated. ID was found in 159 (53%) patients. Patients with ID had a worse prognosis with a higher combined endpoint of all-cause mortality and HF hospitalization after 4years of follow-up (log rank=0.008). Pulmonary hypertension, depression, and thyroid disease were more prevalent in the ID group. Multivariable analysis showed that ID was independently associated with body mass index (P=0.003), pulmonas no longer significantly associated with a reduced exercise capacity. This reflects that impaired exercise capacity in HFpEF is complex and seems multifactorial. Interestingly, pulmonary hypertension was an independent predictor of both ID and exercise capacity.

The pollen beetle (Brassicogethes aeneus) is the most abundant pest of oilseed rape in spring and is potentially one of the most damaging. Adults feed on the pollen within closed flower buds and the damage leads to bud abscission, resulting in podless stalks and yield reduction. Several methods are currently used to monitor the pressure of this insect, such as counting the numbers of adults on the plants, quantifying the number of buds damaged by the insect before flowering or counting the number of podless stalks before harvest. We conducted experiments to evaluate the robustness of these sampling methods and compared their results. We also describe how pollen beetles damage the plants to understand the limitations of methods based on damage estimation.

Methods based on adult abundance lack robustness. We observed that most of the damage to buds is caused by pollen beetles feeding on small buds (< 3 mm), and that this damage can be quantified later in the season, indicating that methods based on the count of podless stalks are robust.