Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors.

Filoviridae, including Ebola (EBOV) and Marburg (MARV) viruses, are emerging pathogens that pose a serious threat to public health. No agents have been approved to treat filovirus infections, representing a major unmet medical need. The selective estrogen receptor modulator (SERM) toremifene was previously identified from a screen of FDA-approved drugs as a potent EBOV viral entry inhibitor, via binding to EBOV glycoprotein (GP).

HybridSucc: A Hybrid-learning Architecture for General and Species-specific Succinylation Site Prediction.

As an important protein acylation modification, lysine succinylation (Ksucc) is involved in diverse biological processes, and participates in human tumorigenesis. Here, we collected 26,243 non-redundant known Ksucc sites from 13 species as the benchmark data set, combined 10 types of informative features, and implemented a hybrid-learning architecture by integrating deep-learning and conventional machine-learning algorithms into a single framework. We constructed a new tool named HybridSucc, which achieved area under curve (AUC) values of 0.

The short-term effect of PM/O on daily mortality from 2013 to 2018 in Hefei, China.

This research intends to explore the short-term impacts of PM/O on daily death in Hefei from 2013 to 2018. Data on daily death of Hefei residents, meteorological factors, and air pollutants were collected from Jan 1, 2013, to Dec 31, 2018. The correlation between PM/O and daily death in Hefei during the research period was studied by time series analysis.

Genome-wide adaptive evolution to underground stresses in subterranean mammals: Hypoxia adaption, immunity promotion, and sensory specialization.

Life underground has provided remarkable examples of adaptive evolution in subterranean mammals; however, genome-wide adaptive evolution to underground stresses still needs further research. There are approximately 250 species of subterranean mammals across three suborders and six families. These species not only inhabit hypoxic and dark burrows but also exhibit evolved adaptation to hypoxia, cancer resistance, and specialized sensory systems, making them an excellent model of evolution.

Disturbance mechanisms of lacustrine organic carbon burial: Case study of Cuopu Lake, Southwest China.

Lakes are important organic carbon (OC) traps in the global carbon cycle. Recent studies have shown that the rate of OC burial in lacustrine sediments is influenced by factors such as climate change, land-use change, and eutrophication. In this study, we use multiproxy methods to reveal the mechanisms of lacustrine sediment OC burial in an alpine lake (Cuopu Lake), in southwest China.

Stimuli-Enabled Artificial Synapses for Neuromorphic Perception: Progress and Perspectives.

Brain-inspired neuromorphic computing is intended to provide effective emulation of the functionality of the human brain via the integration of electronic components. Recent studies of synaptic plasticity, which represents one of the most significant neurochemical bases of learning and memory, have enhanced the general comprehension of how the brain functions and have thereby eased the development of artificial neuromorphic devices. An understanding of the synaptic plasticity induced by various types of stimuli is essential for neuromorphic system construction.

Development of coumarine derivatives as potent anti-filovirus entry inhibitors targeting viral glycoprotein.

Filoviruses, including Ebolavirus (EBOV), Marburgvirus (MARV) and Cuevavirus, cause hemorrhagic fevers in humans with up to 90% mortality rates. In the 2014-2016 West Africa Ebola epidemic, there are 15,261 laboratory confirmed cases and 11,325 total deaths. The lack of effective vaccines and medicines for the prevention and treatment of filovirus infection in humans stresses the urgency to develop antiviral therapeutics against filovirus-associated diseases.

Advances in nanomaterials for treatment of hypoxic tumor.

The hypoxic tumor microenvironment is characterized by disordered vasculature and rapid proliferation of tumors, resulting from tumor invasion, progression and metastasis. The hypoxic conditions restrict efficiency of tumor therapies, such as chemotherapy, radiotherapy, phototherapy and immunotherapy, leading to serious results of tumor recurrence and high mortality. Recently, research has concentrated on developing functional nanomaterials to treat hypoxic tumors.

Comparative phosphoproteomic analysis of BR-defective mutant reveals a key role of GhSK13 in regulating cotton fiber development.

Brassinosteroid (BR), a steroid phytohormone, whose signaling transduction pathways include a series of phosphorylation and dephosphorylation events, and GSK3s are the main negative regulator kinases. BRs have been shown to play vital roles in cotton fiber elongation. However, the underlying mechanism is still elusive.

An orally delivered microbial cocktail for the removal of nitrogenous metabolic waste in animal models of kidney failure.

Patients with kidney failure commonly require dialysis to remove nitrogenous wastes and to reduce burden to the kidney. Here, we show that a bacterial cocktail orally delivered in animals with kidney injury can metabolize blood nitrogenous waste products before they diffuse through the intestinal mucosal barrier. The microbial cocktail consists of three strains of bacteria isolated from faecal microbiota that metabolize urea and creatinine into amino acids, and is encapsulated in calcium alginate microspheres coated with a polydopamine layer that is selectively permeable to small-molecule nitrogenous wastes.

Systematic Analysis of the Aberrances and Functional Implications of Ferroptosis in Cancer.

Ferroptosis is a type of cell death related to cancer; however, the characteristics of ferroptosis in cancers are still uncertain. Based on the data in The Cancer Genome Atlas, we found that most ferroptosis regulator genes (FRGs) were differentially expressed in tumors, somatic copy number alterations (SCNA) and DNA methylation contributed to their aberrant expression. We established the ferroptosis potential index (FPI) to reveal the functional roles of ferroptosis and noticed that the FPI was higher in tumors than in normal tissues in most cancers and was associated with subtypes and clinical features.

Surface Nitrogen-Injection Engineering for High Formation Rate of CO Reduction to Formate.

In this study, we highlight that surface nitrogen-injection engineering brings a high formation rate for CO reduction to formate, which is high level among the reported electrocatalysts. Surface nitrogen-injection engineering can increase the amounts of active sites and optimize the electronic structure simultaneously. Taking an example of SnS precursors, the final-obtained surface N-enriched Sn(S) nanosheets (denoted as N-Sn(S) nanosheets) exhibit a 5-fold of current density and 2.

Structure of avian influenza hemagglutinin in complex with a small molecule entry inhibitor.

HA plays a critical role in influenza infection and, thus HA is a potential target for antivirals. Recently, our laboratories have described a novel fusion inhibitor, termed CBS1117, with EC ∼3 μM against group 1 HA. In this work, we characterize the binding properties of CBS1117 to avian H5 HA by x-ray crystallography, NMR, and mutagenesis.

gutMEGA: a database of the human gut MEtaGenome Atlas.

The gut microbiota plays important roles in human health through regulating both physiological homeostasis and disease emergence. The accumulation of metagenomic sequencing studies enables us to better understand the temporal and spatial variations of the gut microbiota under different physiological and pathological conditions. However, it is inconvenient for scientists to query and retrieve published data; thus, a comprehensive resource for the quantitative gut metagenome is urgently needed.

Discovery and Structural Optimization of 4-(Aminomethyl)benzamides as Potent Entry Inhibitors of Ebola and Marburg Virus Infections.

The recent Ebola epidemics in West Africa underscore the great need for effective and practical therapies for future Ebola virus outbreaks. We have discovered a new series of remarkably potent small molecule inhibitors of Ebola virus entry. These 4-(aminomethyl)benzamide-based inhibitors are also effective against Marburg virus.

Identification and expression analysis of the DREB transcription factor family in pineapple ( (L.) Merr.).

Background: Dehydration responsive element-binding (DREB) transcription factors play a crucial role in plant growth, development and stress responses. Although genes have been characterized in many plant species, genome-wide identification of the gene family has not yet been reported in pineapple ( (L.) Merr.

Author Correction: Bis-biguanide dihydrochloride inhibits intracellular replication of M. tuberculosis and controls infection in mice.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Bacterial community composition in soils covered by different vegetation types in the Yancheng tidal marsh.

Coastal wetland vegetation plays an important role in maintaining ecological function and is a key factor affecting the soil bacterial community. Spartina alterniflora was introduced to the Yancheng tidal marsh to stabilize the sediments and gradually replaced the native plants. However, the changes in the soil bacterial community profile caused by S.

Effective Gene Knockout by AdV-Delivered CRISPR/Cas9 in Postnatal Chick Leg Muscle.

Muscle growth and development are important aspects of chicken meat production, but the underlying regulatory mechanisms remain unclear and need further exploration. CRISPR has been used for gene editing to study gene function in mice, but less has been done in chick muscles. To verify whether postnatal gene editing could be achieved in chick muscles and determine the transcriptomic changes, we knocked out (), a potential inhibitor of muscle growth and development, in chicks and performed transcriptome analysis on knock-out (KO) muscles and wild-type (WT) muscles at two post-natal days: 3d (3-day-old) and 14d (14-day-old).

Transcriptome analysis of the response provided by to severe hypoxia includes enhancing DNA repair and damage prevention.

Background: Severe hypoxia induces a series of stress responses in mammals; however, subterranean rodents have evolved several adaptation mechanisms of energy metabolisms and O utilization for hypoxia. Mammalian brains show extreme aerobic metabolism. Following hypoxia exposure, mammals usually experience irreversible brain damage and can even develop serious diseases, such as hypoxic ischemic encephalopathy and brain edema.

Bottom-up preparation of hierarchically porous MOF-modified carbon sphere derivatives for efficient oxygen reduction.

The rational design and controllable preparation of carbon-based catalysts for oxygen reduction reactions (ORRs) are at the core of key technologies for fuel cells and chargeable batteries in the field of advanced energy conversion and storage. In the present study, a Co species was synthesized by tuning the Zn dopant content in a bimetallic zeolitic-imidazolate framework functionalized with carbon spheres (CoZn-ZIF/CS). Using CoZn-ZIF/CS as the precursor, Co nanoparticles on N-doped carbon spheres were generated at 1000 °C (CoZn-ZIF/CS-1000).

Deep learning based prediction of species-specific protein S-glutathionylation sites.

As a widespread and reversible post-translational modification of proteins, S-glutathionylation specifically generates the mixed disulfides between cysteine residues and glutathione, which regulates various biological processes including oxidative stress, nitrosative stress and signal transduction. The identification of proteins and specific sites that undergo S-glutathionylation is crucial for understanding the underlying mechanisms and regulatory effects of S-glutathionylation. Experimental identification of S-glutathionylation sites is laborious and time-consuming, whereas computational predictions are more attractive due to their high speed and convenience.

Identification of entry inhibitors with 4-aminopiperidine scaffold targeting group 1 influenza A virus.

Influenza A viruses (IAVs) cause seasonal flu and occasionally pandemics. The current therapeutics against IAVs target two viral proteins - neuraminidase (NA) and M2 ion-channel protein. However, M2 ion channel inhibitors (amantadine and rimantadine) are no longer recommended by CDC for use due to the emergence of high level of antiviral resistance among the circulating influenza viruses, and resistant strains to NA inhibitors (oseltamivir and zanamivir) have also been reported.

Spatial econometric analysis of environmental total factor productivity of ranimal husbandry and its influencing factors in China during 2001-2017.

Pollution discharge from animal husbandry deteriorates the environment and is of global concern. In this study, data envelopment analysis (DEA) was used to indirectly estimate the pollution discharge of livestock and poultry breeding in terms of sustainable development in China. Land, biogas, and grassland were included as input indexes, and the inverted values of indexes of organic matter, nitrogen, and phosphorus produced by pigs, dairy cattle, beef cattle, poultry, and sheep were included as output indexes.