FusionPDB: a knowledgebase of human fusion proteins.

Tumorigenic functions due to the formation of fusion genes have been targeted for cancer therapeutics (i.e. kinase inhibitors). However, many fusion proteins involved in various cellular processes have not been studied for targeted therapeutics. This is because the lack of complete fusion protein sequences and their whole 3D structures has made it challenging to develop new therapeutic strategies. To fill these critical gaps, we developed a computational pipeline and a resource of human fusion proteins named FusionPDB, available at https://compbio.uth.edu/FusionPDB. FusionPDB is organized into four levels: 43K fusion protein sequences (14.7K in-frame fusion genes, Level 1), over 2300 + 1267 fusion protein 3D structures (from 2300 recurrent and 266 manually curated in-frame fusion genes, Level 2), pLDDT score analysis for the 1267 fusion proteins from 266 manually curated fusion genes (Level 3), and virtual screening outcomes for 68 selected fusion proteins from 266 manually curated fusion genes (Level 4). FusionPDB is the only resource providing whole 3D structures of fusion proteins and comprehensive knowledge of human fusion proteins. It will be regularly updated until it covers all human fusion proteins in the future.

Anthocyanin biosynthesis in goji berry is inactivated by deletion in a bHLH transcription factor LrLAN1b promoter.

Black goji berry (Lycium ruthenicum Murray) contains a rich source of health-promoting anthocyanins which are used in herbal medicine and nutraceutical foods in China. A natural variant producing white berries allowed us to identify two key genes involved in the regulation of anthocyanin biosynthesis in goji berries: one encoding a MYB transcription factor (LrAN2-like) and one encoding a basic helix-loop-helix (bHLH) transcription factor (LrAN1b). We previously found that LrAN1b expression was lost in the white berry variant, but the molecular basis for this phenotype was unknown. Here, we identified the molecular mechanism for loss of anthocyanins in white goji berries. In white goji, the LrAN1b promoter region has a 229 bp deletion that removes three MYB-binding elements and one bHLH-binding element, which are key to its expression. Complementation of the white goji berry LrAN1b allele with the LrAN1b promoter restored pigmentation. Virus-induced gene silencing of LrAN1b in black goji berry reduced fruit anthocyanin biosynthesis. Molecular analyses showed that LrAN2-like and another bHLH transcription factor LrJAF13 can activate LrAN1b by binding directly to the MYB-recognizing element and bHLH-recognizing element of its promoter-deletion region. LrAN1b expression is enhanced by the interaction of LrAN2-like with LrJAF13 and the WD40 protein LrAN11. LrAN2-like and LrAN11 interact with either LrJAF13 or LrAN1b to form two MYB-bHLH-WD40 complexes, which hierarchically regulate anthocyanin biosynthesis in black goji berry. This study on a natural variant builds a comprehensive anthocyanin regulatory network that may be manipulated to tailor goji berry traits.

α-d-Glucose-1,6-Biphosphate Induces Dendritic Cell Homing to Enhance the Antitumor Effect of Neoantigen Vaccines.

Neoantigen vaccines have achieved good therapeutic effects in animal experiments and early clinical trials on certain malignant tumors. However, their overall objective effectiveness in clinical trials still needs to be improved. Low-efficiency dendritic cell (DC) migration (<5%) to lymph nodes is one of the factors that limits vaccine effectiveness. For neoantigen vaccines, improving the homing efficiency of DCs is expected to further improve the immunotherapeutic effect. In this study, we used α-d-glucose-1,6-biphosphate (α-d-Glu), a metabolite that successfully enhanced C57BL/6J mouse bone marrow-derived DC homing induced by neoantigen peptide, mRNA, and DC vaccines during the administration process and improved the antitumor effects in the mouse C57BL/6J model with a neoantigen vaccine. We clarified that α-d-Glu activated MAPK8IP1 by inhibiting the expression of microRNA-10a-5p, thereby activating the MAPK signaling pathway to promote DC homing. Excitingly, the efficiency of α-d-Glu in promoting DC migration is not weaker than that of PGE2, which is the gold standard used to promote DC migration in clinical trials of DC vaccines. Thus, this study lays the foundation for further enhancing the objective clinical response rate of neoantigen vaccines and overcoming the limitation of an insufficient clinical response rate for neoantigen vaccines caused by low DC homing efficiency.

Multimodal optoacoustic imaging: methods and contrast materials.

Optoacoustic (OA) imaging offers powerful capabilities for interrogating biological tissues with rich optical absorption contrast while maintaining high spatial resolution for deep tissue observations. The spectrally distinct absorption of visible and near-infrared photons by endogenous tissue chromophores facilitates extraction of diverse anatomic, functional, molecular, and metabolic information from living tissues across various scales, from organelles and cells to whole organs and organisms. The primarily blood-related contrast and limited penetration depth of OA imaging have fostered the development of multimodal approaches to fully exploit the unique advantages and complementarity of the method. We review the recent hybridization efforts, including multimodal combinations of OA with ultrasound, fluorescence, optical coherence tomography, Raman scattering microscopy and magnetic resonance imaging as well as ionizing methods, such as X-ray computed tomography, single-photon-emission computed tomography and positron emission tomography. Considering that most molecules absorb light across a broad range of the electromagnetic spectrum, the OA interrogations can be extended to a large number of exogenously administered small molecules, particulate agents, and genetically encoded labels. This unique property further makes contrast moieties used in other imaging modalities amenable for OA sensing.

Reconfigurable Ag/HfO2/NiO/Pt Memristors with Stable Synchronous Synaptic and Neuronal Functions for Renewable Homogeneous Neuromorphic Computing System.

Artificial synapses and bionic neurons offer great potential in highly efficient computing paradigms. However, complex requirements for specific electronic devices in neuromorphic computing have made memristors face the challenge of process simplification and universality. Herein, reconfigurable Ag/HfO2/NiO/Pt memristors are designed for feasible switching between volatile and nonvolatile modes by compliance current controlled Ag filaments, which enables stable and reconfigurable synaptic and neuronal functions. A neuromorphic computing system effectively replicates the biological synaptic weight alteration and continuously accomplishes excitation and reset of artificial neurons, which consist of bionic synapses and artificial neurons based on isotype Ag/HfO2/NiO/Pt memristors. This reconfigurable electrical performance of the Ag/HfO2/NiO/Pt memristors takes advantage of simplified hardware design and delivers integrated circuits with high density, which exhibits great potency for future neural networks.

An Observational Prospective Cohort Study of Vaccine Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection of an Aerosolized, Inhaled Adenovirus Type 5-Vectored Coronavirus Disease 2019 Vaccine Given as a Second Booster Dose in Guangzhou City, China.

Using a prospective, observational cohort study during the post-"dynamic COVID-zero" wave in China, we estimated short-term relative effectiveness against Omicron BA.5 infection of inhaled aerosolized adenovirus type 5-vectored ancestral strain coronavirus disease 2019 (COVID-19) vaccine as a second booster dose approximately 1 year after homologous boosted primary series of inactivated COVID-19 vaccine compared with no second booster. Participants reported nucleic acid or antigen test results weekly until they tested positive or completed predesignated follow-up. After excluding participants infected <14 days after study entry, relative effectiveness among the 6576 participants was 61% in 18- to 59-year-olds and 38% in ≥60-year-olds and was sustained for 12 weeks.

AStruct: detection of allele-specific RNA secondary structure in structuromic probing data.

BACKGROUND: Uncovering functional genetic variants from an allele-specific perspective is of paramount importance in advancing our understanding of gene regulation and genetic diseases. Recently, various allele-specific events, such as allele-specific gene expression, allele-specific methylation, and allele-specific binding, have been explored on a genome-wide scale due to the development of high-throughput sequencing methods. RNA secondary structure, which plays a crucial role in multiple RNA-associated processes like RNA modification, translation and splicing, has emerged as an essential focus of relevant research. However, tools to identify genetic variants associated with allele-specific RNA secondary structures are still lacking. RESULTS: Here, we develop a computational tool called 'AStruct' that enables us to detect allele-specific RNA secondary structure (ASRS) from RT-stop based structuromic probing data. AStruct shows robust performance in both simulated datasets and public icSHAPE datasets. We reveal that single nucleotide polymorphisms (SNPs) with higher AStruct scores are enriched in coding regions and tend to be functional. These SNPs are highly conservative, have the potential to disrupt sites involved in m6A modification or protein binding, and are frequently associated with disease. CONCLUSIONS: AStruct is a tool dedicated to invoke allele-specific RNA secondary structure events at heterozygous SNPs in RT-stop based structuromic probing data. It utilizes allelic variants, base pairing and RT-stop information under different cell conditions to detect dynamic and functional ASRS. Compared to sequence-based tools, AStruct considers dynamic cell conditions and outperforms in detecting functional variants. AStruct is implemented in JAVA and is freely accessible at: https://github.com/canceromics/AStruct .

A Type of Chiral C2-Symmetric Arylthiol Catalyst for Highly Enantioselective Anti-Markovnikov Hydroamination.

The development of chiral hydrogen donor catalysts is fundamental in the expansion and innovation of asymmetric organocatalyzed reactions via an enantioselective hydrogen atom transfer (HAT) process. Herein, an unprecedented type of chiral C2-symmetric arylthiol catalysts derived from readily available enantiomeric lactate ester was developed. With these catalysts, an asymmetric anti-Markovnikov alkene hydroamination-cyclization reaction was established, affording a variety of pharmaceutically interesting 3-substituted piperidines with moderate to high enantioselectivity. Results of the designed control experiments and theoretical computation rationalized the origin of stereocontrol and disclosed the spatial effect of the moiety of chiral thiols on the enantioselectivity. We believed the facile synthesis, flexible tunability, and effective enantioselectivity-controlling capability of these catalysts would shed light on the development of versatile chiral HAT catalysts and related asymmetric reactions.

Selective Capacitive Removal of Pb2+ from Wastewater over Biochar Electrodes by Zinc Regulation.

Biochar materials have shown great potential for broad catalytic application. However, using these materials in the capacitive deionization technology (CDI) system for heavy metal removal still faces a significant challenge due to their low specific capacity and removal capability. Here, a comprehensive regulation on the interfacial/bulk electrochemistry of biochar by Zn doping is reported, which suggests a high renewable capacity (20 mg g-1) and outstanding selective capacitive removal ability (SCR) of Pb2+ from leachate. The SCR efficiency of Pb2+ is as high as 99% compared to K+ (8%), Na+ (13%), and Cd2+ (37%). This work proves that the doped Zn on the biochar can combine with OH- generated by water splitting to form M─OH bonds, which is beneficial for improving the specific capacity. Significantly, the relationship between double-layer capacitance and pseudo-capacitance can also be optimized by regulating the content of Zn, leading to different removal abilities of heavy metals. Therefore, this work offers insights into charge-storage kinetics, which provide valuable guidelines for designing and optimizing the biochar electrode for broader environmental applications.

Platelet-Derived Growth Factor Nanocapsules with Tunable Controlled Release for Chronic Wound Healing.

Chronic wounds have emerged as an increasingly critical clinical challenge over the past few decades, due to their increasing incidence and socioeconomic burdens. Platelet-derived growth factor (PDGF) plays a pivotal role in regulating processes such as fibroblast migration, proliferation, and vascular formation during the wound healing process. The delivery of PDGF offers great potential for expediting the healing of chronic wounds. However, the clinical effectiveness of PDGF in chronic wound healing is significantly hampered by its inability to maintain a stable concentration at the wound site over an extended period. In this study, a controlled PDGF delivery system based on nanocapsules is proposed. In this system, PDGF is encapsulated within a degradable polymer shell. The release rate of PDGF from these nanocapsules can be precisely adjusted by controlling the ratios of two crosslinkers with different degradation rates within the shells. As demonstrated in a diabetic wound model, improved therapeutic outcomes with PDGF nanocapsules (nPDGF) treatment are observed. This research introduces a novel PDGF delivery platform that holds promise for enhancing the effectiveness of chronic wound healing.