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The field of neuroimmunology has changed dramatically over the last ten years [...].

Background Internal ribosome entry sites (IRES) are segments of mRNA found in untranslated regions that can recruit the ribosome and initiate translation independently of the 5′ cap-dependent translation initiation mechanism. IRES usually function when 5′ cap-dependent translation initiation has been blocked or repressed. They have been widely found to play important roles in viral infections and cellular processes. However, a limited number of confirmed IRES have been reported due to the requirement for highly labor intensive, slow, and low efficiency laboratory experiments. Bioinformatics tools have been developed, but there is no reliable online tool. Results This paper systematically examines the features that can distinguish IRES from non-IRES sequences. Sequence features such as kmer words, structural features such as Q MFE , and sequence/structure hybrid features are evaluated as possible discriminators. They are incorporated into an IRES classifier based on XGBoost. The XGBoost model performs better than previous classifiers, with higher accuracy and much shorter computational time. The number of features in the model has been greatly reduced, compared to previous predictors, by including global kmer and structural features. The contributions of model features are well explained by LIME and SHapley Additive exPlanations. The trained XGBoost model has been implemented as a bioinformatics tool for IRES prediction, IRESpy ( https://irespy.shinyapps.io/IRESpy/ ), which has been applied to scan the human 5′ UTR and find novel IRES segments. Conclusions IRESpy is a fast, reliable, high-throughput IRES online prediction tool. It provides a publicly available tool for all IRES researchers, and can be used in other genomics applications such as gene annotation and analysis of differential gene expression.

Organic semiconductors offer a tunable platform for photocatalysis, yet the more difficult exciton dissociation, compared to that in inorganic semiconductors, lowers their photocatalytic activities. In this work, we report that the charge carrier lifetime is dramatically prolonged by incorporating a suitable donor-acceptor (β-ketene-cyano) pair into a covalent organic framework nanosheet. These nanosheets show an apparent quantum efficiency up to 82.6% at 450 nm using platinum as co-catalyst for photocatalytic H 2 evolution. Charge carrier kinetic analysis and femtosecond transient absorption spectroscopy characterizations verify that these modified covalent organic framework nanosheets have intrinsically lower exciton binding energies and longer-lived charge carriers than the corresponding nanosheets without the donor-acceptor unit. This work provides a model for gaining insight into the nature of short-lived active species in polymeric organic photocatalysts. While organic semiconductors offer a tunable platform for photocatalysis, they often show worse performances. Here, authors examine how a donor-acceptor pair’s incorporation into a covalent organic framework boosts photocatalytic H 2 evolution performances with a platinum co-catalyst.

Many continental shelves tend to steepen landward. Existing models attribute this curvature to a progressive attenuation of the effect of postglacial sea‐level rise or sediment redistribution by modern coastal‐marine processes. Here, we present an alternative framework in which shelf curvature arises from an inherent self‐organizing mechanism. During sea‐level rise, if the critical length of the downstream alluvial river is exceeded, deltaic sedimentation cannot be sustained. In this non‐deltaic transgressive regime, the alluvial aggradation rate autogenically increases as the river shrinks, enhancing alluvial sediment accumulation and producing a steeper local shelf slope closer to the shoreline. Two‐dimensional geometric modeling reveals a simple governing equation for the self‐organized curvature of the shelf profile, with support from flume‐tank experiments and applications to modern systems, providing a mechanistic basis for interpreting existing shelf profiles. Plain Language Summary A shelf is the marginal zone of a continent that extends shallowly into the sea. Modern shelves are characterized by different shapes and sizes; they can be steep or gentle, wide or narrow, and control the physicochemical processes and thus the ecosystem of the shallow sea. Throughout Earth's history, shelves have been important geological interfaces that are repeatedly created and filled with sediment in response to sea‐level rise and fall, thereby forming strata. A common feature of many shelves is that they have a concave upward profile that steepens in the landward direction. Such a curvature pattern is typically interpreted as the result of wave erosion or an increasing contribution of upstream sediment input. Here, we show that the landward steepening of the shelf is an autogenic behavior caused by an inherent mechanism. Owing to this inherent mechanism, the shelf has a theoretical profile that is determined by the terrestrial hinterland and alluvial slopes. Given similar background slope conditions, shelves differ in shape and scale because they develop at different stages corresponding to different segments along the theoretical curve. The autogenic landward‐steepening mechanism provides a new interpretation of shelf genesis. Key Points During transgression, deltaic sedimentation cannot be sustained if the length of the downstream alluvial river exceeds the threshold The non‐deltaic transgressive shelf steepens landward, reflecting autogenic shrinkage of the feeder alluvial system The governing equation for the shelf profile is supported by two‐dimensional physical experiments and applications in natural systems

In the field of perovskite light-emitting diodes (PeLEDs), the performance of blue emissive electroluminescence devices lags behind the other counterparts due to the lack of fabrication methodology. Herein, we demonstrate the in situ fabrication of CsPbClBr 2 nanocrystal films by using mixed ligands of 2-phenylethanamine bromide (PEABr) and 3,3-diphenylpropylamine bromide (DPPABr). PEABr dominates the formation of quasi-two-dimensional perovskites with small- n domains, while DPPABr induces the formation of large- n domains. Strong blue emission at 470 nm with a photoluminescence quantum yield up to 60% was obtained by mixing the two ligands due to the formation of a narrower quantum-well width distribution. Based on such films, efficient blue PeLEDs with a maximum external quantum efficiency of 8.8% were achieved at 473 nm. Furthermore, we illustrate that the use of dual-ligand with respective tendency of forming small- n and large- n domains is a versatile strategy to achieve narrow quantum-well width distribution for photoluminescence enhancement. Designing efficient blue perovskite LEDs by using mixed halides perovskite is still a challenge, limited mainly by the phase segregation issue. Here, the authors demonstrate in situ fabrication of quasi-2D CsPbClBr2 nanocrystal films with mixed ligands to overcome the constraint.

In cluster analysis, one of the major challenges is to estimate the number of clusters. Most existing approaches attempt to minimize some distance-based dissimilarity measure within clusters. This article proposes a novel selection criterion that is applicable to all kinds of clustering algorithms, including distance based or non-distance based algorithms. The key idea is to select the number of clusters that minimizes the algorithm's instability, which measures the robustness of any given clustering algorithm against the randomness in sampling.Anovel estimation scheme for clustering instability is developed based on crossvalidation. The proposed selection criterion's effectiveness is demonstrated on a variety of numerical experiments, and its asymptotic selection consistency is established when the dataset is properly split.

The polysaccharides isolated and purified from different parts of the medicinal fungus Cordyceps cicadae were identified, and three extracts displaying significant biological activities were selected for further study. The bacterium substance polysaccharides (BSP), spore powder polysaccharides (SPP), and pure powder polysaccharides (PPP) were separated, purified, and collected from the sclerotia, spores, and fruiting bodies of Cordyceps cicadae, respectively. The structures of Cordyceps cicadae polysaccharides were analyzed using gas chromatography, Fourier-transform infrared spectroscopy, methylation analysis, and one-dimensional (1H and 13C) nuclear magnetic resonance spectroscopy. Moreover, the hypoglycemic effect of Cordyceps cicadae polysaccharides was examined in both in vitro and in vivo models. BSP, SPP, and PPP significantly increased glucose absorption in HepG2 cells, and alleviated insulin resistance (IR) in the in vitro model. SPP was the most effective, and was therefore selected for further study of its hypoglycemic effect in vivo. SPP effectively improved body weight and glucose and lipid metabolism in type 2 diabetes model mice, in addition to exerting a protective effect on liver injury. SPP regulated the mRNA expression of key PI3K/Akt genes involved in the insulin signaling pathway. The hypoglycemic mechanism of SPP may reduce hepatic insulin resistance by activating the PI3K/Akt signaling pathway. Spore powder polysaccharides (SPP) extracted from Cordyceps cicadae effectively improved body weight and glucose and lipid metabolism in type 2 diabetes model mice, in addition to exerting a protective effect on liver injury. The mechanism underlying the hypoglycemic effect of SPP regulates the mRNA expression of key PI3K/Akt genes involved in the insulin signaling pathway to alleviate insulin resistance. Our results provide a theoretical basis for research into the hypoglycemic effect of Cordyceps cicadae, and lay the foundation for the development of functional products.

A key process underlying the application of low-dimensional, quantum-confined semiconductors in energy conversion is charge transfer from these materials, which, however, has not been fully understood yet. Extensive studies of charge transfer from colloidal quantum dots reported rates increasing monotonically with driving forces, never displaying an inverted region predicted by the Marcus theory. The inverted region is likely bypassed by an Auger-like process whereby the excessive driving force is used to excite another Coulomb-coupled charge. Herein, instead of measuring charge transfer from excitonic states (coupled electron-hole pairs), we build a unique model system using zero-dimensional quantum dots or two-dimensional nanoplatelets and surface-adsorbed molecules that allows for measuring charge transfer from transiently-populated, single-charge states. The Marcus inverted region is clearly revealed in these systems. Thus, charge transfer from excitonic and single-charge states follows the Auger-assisted and conventional Marcus charge transfer models, respectively. This knowledge should enable rational design of energetics for efficient charge extraction from low-dimensional semiconductor materials as well as suppression of the associated energy-wasting charge recombination. Marcus inverted region for charge transfer from low-dimensional semiconductor materials has been long sought after. Here, the authors reveal this region by directly measuring charge transfer from single-charge states rather than excitonic states.