ProT-Diff: A Modularized and Efficient Strategy for De Novo Generation of Antimicrobial Peptide Sequences by Integrating Protein Language and Diffusion Models.

Antimicrobial peptides (AMPs) are a promising solution for treating antibiotic-resistant pathogens. However, efficient generation of diverse AMPs without prior knowledge of peptide structures or sequence alignments remains a challenge. Here, ProT-Diff is introduced, a modularized deep generative approach that combines a pretrained protein language model with a diffusion model for the de novo generation of AMPs sequences.

Construction of AlGaN/GaN high-electron-mobility transistor-based biosensor for ultrasensitive detection of SARS-CoV-2 spike proteins and virions.

The COVID-19 pandemic has highlighted the need for rapid and sensitive detection of SARS-CoV-2. Here, we report an ultrasensitive SARS-CoV-2 immunosensor by integration of an AlGaN/GaN high-electron-mobility transistor (HEMT) and anti-SARS-CoV-2 spike protein antibody. The AlGaN/GaN HEMT immunosensor has demonstrated the capability to detect SARS-CoV-2 spike proteins at an impressively low concentration of 10 M.

Two-Dimensional Protein Nanoarray as a Carrier of Sensing Elements for Gold-Based Immunosensing Systems.

Homogeneous and high-density immobilization of proteins on gold-based sensing surface without the loss of protein activity is of great significance for high-performance immunosensing but remains challenging. To realize more sensitive immunosensing, an improved method for protein immobilization on the gold surface is urgently required. Here, we propose a biological and mild approach by combining a genetically encoded SpyTag-SpyCatcher interaction system with a redesigned S-layer of bacteria.

A Cancer Cell Membrane-Derived Biomimetic Nanocarrier for Synergistic Photothermal/Gene Therapy by Efficient Delivery of CRISPR/Cas9 and Gold Nanorods.

Bimodal synergistic therapy produces superadditive effect for enhanced therapeutic efficacy. However, how to efficiently and simultaneously deliver several kinds of therapeutic agents is still challenging. A cancer cell membrane-derived nanocarrier (mCas9-sGNRs) is proposed for synergistic photothermal/gene therapy (PTT/GT) by efficient delivery of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) and gold nanorods (GNRs).

Biosensors for the Detection of .

, present in two forms of vegetative cells and spores, is a pathogen that infects humans through contact with infected animals or contaminated animal products and is also maliciously used in terrorist acts. Therefore, a rapid and sensitive test for is necessary but challenging. The challenge comes from the following aspects: an accurate distinction of from other species due to their high genomic similarity and the horizontal gene transfer between members; direct detection of the spores without damaging them for component extraction to avoid the risk of spore atomization; and the rapid detections of in complex samples, such as soil and suspicious powders, without sample pretreatments and expensive large-scale equipment.

Simultaneous Detection of a Cluster of Differentiation Markers on Leukemia-Derived Exosomes by Multiplex Immuno-Polymerase Chain Reaction via Capillary Electrophoresis Analysis.

Acute myeloid leukemia (AML) is a heterogeneous disease, and there are critical interests in detecting multiple biomarkers as a single biomarker detection cannot reflect the exact phase of the disease. Exosomes derived from different types of AML cells contain respective combinations of cluster of differentiation (CD) markers that may be used to guide the molecular typing of AML in the clinic. Here, aiming to build more precise molecular typing of AML, we demonstrate multiplex immuno-PCR (mI-PCR) assay for simultaneous detection of multiple surface CDs on exosomes of AML via capillary electrophoresis with laser-induced fluorescence (CE-LIF).

Molecular Diagnosis of COVID-19: Challenges and Research Needs.

Molecular diagnosis of COVID-19 primarily relies on the detection of RNA of the SARS-CoV-2 virus, the causative infectious agent of the pandemic. Reverse transcription polymerase chain reaction (RT-PCR) enables sensitive detection of specific sequences of genes that encode the RNA dependent RNA polymerase (RdRP), nucleocapsid (N), envelope (E), and spike (S) proteins of the virus. Although RT-PCR tests have been widely used and many alternative assays have been developed, the current testing capacity and availability cannot meet the unprecedented global demands for rapid, reliable, and widely accessible molecular diagnosis.

CRISPR-based genomic loci labeling revealed ordered spatial organization of chromatin in living diploid human cells.

The eukaryotic genome is compacted in the form of chromatin within the nucleus. Whether the spatial distribution of the genome is ordered or not has been a longstanding question. Answering this question would enable us to understand nuclear organization and cellular processes more deeply.

A dual-signal amplification platform for sensitive fluorescence biosensing of leukemia-derived exosomes.

Exosomes as nanosized biomarkers hold great potential for the diagnosis of cancer. However, the low concentration of cancer-derived exosomes present in biofluids makes early diagnosis strenuous. Here, we developed a fluorescent biosensing platform, namely a dual signal amplification, for the ultrasensitive detection of leukemia cell-derived exosomes.

Mutagenesis of mNeptune Red-Shifts Emission Spectrum to 681-685 nm.

GFP-like fluorescent proteins with diverse emission wavelengths have been developed through mutagenesis, offering many possible choices in cellular and tissue imaging, such as multi-targets imaging, deep tissue imaging that require longer emission wavelength. Here, we utilized a combined approach of random mutation and structure-based rational design to develop new NIR fluorescent proteins on the basis of a far-red fluorescent protein, mNeptune (Ex/Em: 600/650 nm). We created a number of new monomeric NIR fluorescent proteins with the emission range of 681-685 nm, which exhibit the largest Stocks shifts (77-80 nm) compared to other fluorescent proteins.

Self-Assembly of Ferritin Nanoparticles into an Enzyme Nanocomposite with Tunable Size for Ultrasensitive Immunoassay.

The self-assembly of nanoparticles into larger superstructures is a powerful strategy to develop novel functional nanomaterials, as these superstructures display collective properties that are different to those displayed by individual nanoparticles or bulk samples. However, there are increasing bottlenecks in terms of size control and multifunctionalization of nanoparticle assemblies. In this study, we developed a self-assembly strategy for construction of multifunctional nanoparticle assemblies of tunable size, through rational regulation of the number of self-assembling interaction sites on each nanoparticle.

A S-Layer Protein of Bacillus anthracis as a Building Block for Functional Protein Arrays by In Vitro Self-Assembly.

S-layer proteins create a cell-surface layer architecture in both bacteria and archaea. Because S-layer proteins self-assemble into a native-like S-layer crystalline structure in vitro, they are attractive building blocks in nanotechnology. Here, the potential use of the S-layer protein EA1 from Bacillus anthracis in constructing a functional nanostructure is investigated, and apply this nanostructure in a proof-of-principle study for serological diagnosis of anthrax.

Detection of Bacillus anthracis spores by super-paramagnetic lateral-flow immunoassays based on "Road Closure".

Detection of Bacillus anthracis in the field, whether as a natural infection or as a biothreat remains challenging. Here we have developed a new lateral-flow immunochromatographic assay (LFIA) for B. anthracis spore detection based on the fact that conjugates of B.

The S28H mutation on mNeptune generates a brighter near-infrared monomeric fluorescent protein with improved quantum yield and pH-stability.

For living deep-tissue imaging, the optical window favorable for light penetration is in near-infrared wavelengths, which requires fluorescent proteins with emission spectra in the near-infrared region. Here, we report that a single mutant Ser28His of mNeptune with a near-infrared (≥650 nm) emission maxima of 652 nm is found to improve the brightness, photostability, and pH stability when compared with its parental protein mNeptune, while it remains as a monomer, demonstrating that there is still plenty of room to improve the performance of the existing near infrared fluorescence proteins by directed evolution.

Phosphoproteomic analysis provides novel insights into stress responses in Phaeodactylum tricornutum, a model diatom.

Protein phosphorylation on serine, threonine, and tyrosine (Ser/Thr/Tyr) is well established as a key regulatory posttranslational modification used in signal transduction to control cell growth, proliferation, and stress responses. However, little is known about its extent and function in diatoms. Phaeodactylum tricornutum is a unicellular marine diatom that has been used as a model organism for research on diatom molecular biology.

Rapid detection of Bacillus anthracis spores using a super-paramagnetic lateral-flow immunological detection system.

There is an urgent need for convenient, sensitive, and specific methods to detect the spores of Bacillus anthracis, the causative agent of anthrax, because of the bioterrorism threat posed by this bacterium. In this study, we firstly develop a super-paramagnetic lateral-flow immunological detection system for B. anthracis spores.

Existence of separate domains in lysin PlyG for recognizing Bacillus anthracis spores and vegetative cells.

As a potential antimicrobial, the bacteriophage lysin PlyG has been reported to specifically recognize Bacillus anthracis vegetative cells only and to kill B. anthracis vegetative cells and its germinating spores. However, how PlyG interacts with B.

DNA probe functionalized QCM biosensor based on gold nanoparticle amplification for Bacillus anthracis detection.

The rapid detection of Bacillus anthracis, the causative agent of anthrax disease, has gained much attention since the anthrax spore bioterrorism attacks in the United States in 2001. In this work, a DNA probe functionalized quartz crystal microbalance (QCM) biosensor was developed to detect B. anthracis based on the recognition of its specific DNA sequences, i.

Detection of B. anthracis spores and vegetative cells with the same monoclonal antibodies.

Bacillus anthracis, the causative agent of anthrax disease, could be used as a biothreat reagent. It is vital to develop a rapid, convenient method to detect B. anthracis.

Label-free detection of B. anthracis spores using a surface plasmon resonance biosensor.

This study demonstrates the first use of surface plasmon resonance (SPR) technology for the rapid, sensitive and label-free detection of whole B. anthracis spores. The approach involves the use of an SPR biosensor (Biacore 3000), and a monoclonal antibody which was raised against the B.

Loop-mediated isothermal amplification for rapid detection of Bacillus anthracis spores.

A loop-mediated isothermal amplification (LAMP) assay system was employed for detecting Bacillus anthracis spores in pure cultures as well as in various simulated powder samples. The specificity of the designed LAMP primer sets was validated by assaying 13 B. anthracis strains and 33 non-B.