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.

Standard: human intestine-on-a-chip.

Organs-on-chips are microphysiological systems that allow to replicate the key functions of human organs and accelerate the innovation in life sciences including disease modeling, drug development, and precision medicine. However, due to the lack of standards in their definition, structural design, cell source, model construction, and functional validation, a wide range of translational application of organs-on-chips remains a challenging. "Organs-on-chips: Intestine" is the first group standard on human intestine-on-a-chip in China, jointly agreed and released by the experts from the Chinese Society of Biotechnology on 29th April 2024.

A review on separation and application of plant-derived exosome-like nanoparticles.

Exosomes-like nanoparticles (ELNs) (exosomes or extracellular vesicles) are vesicle-like bodies secreted by cells. Plant ELNs (PENs) are membrane vesicles secreted by plant cells, with a lipid bilayer as the basic skeleton, enclosing various active substances such as proteins and nucleic acids, which have many physiological and pathological functions. Recent studies have found that the PENs are widespread within different plant species and their biological functions are increasingly recognized.

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.

A genetically encoded fluorescent protein sensor for mitochondrial membrane damage detection.

Mitochondria are essential cellular organelles; detecting mitochondrial damage is crucial in cellular biology and toxicology. Compared with existing chemical probe detection methods, genetically encoded fluorescent protein sensors can directly indicate cellular and molecular events without involving exogenous reagents. In this study, we introduced a molecular sensor system, MMD-Sensor, for monitoring mitochondrial membrane damage.

Detection of continuous hierarchical heterogeneity by single-cell surface antigen analysis in the prognosis evaluation of acute myeloid leukaemia.

Background: Acute myeloid leukaemia (AML) is characterised by the malignant accumulation of myeloid progenitors with a high recurrence rate after chemotherapy. Blasts (leukaemia cells) exhibit a complete myeloid differentiation hierarchy hiding a wide range of temporal information from initial to mature clones, including genesis, phenotypic transformation, and cell fate decisions, which might contribute to relapse in AML patients.

Methods: Based on the landscape of AML surface antigens generated by mass cytometry (CyTOF), we combined manifold analysis and principal curve-based trajectory inference algorithm to align myelocytes on a single-linear evolution axis by considering their phenotype continuum that correlated with differentiation order.

Altered hACE2 binding affinity and S1/S2 cleavage efficiency of SARS-CoV-2 spike protein mutants affect viral cell entry.

SARS-CoV-2 variants are constantly emerging, hampering public health measures in controlling the number of infections. While it is well established that mutations in spike proteins observed for the different variants directly affect virus entry into host cells, there remains a need for further expansion of systematic and multifaceted comparisons. Here, we comprehensively studied the effect of spike protein mutations on spike expression and proteolytic activation, binding affinity, viral entry efficiency and host cell tropism of eight variants of concern (VOC) and variants of interest (VOI).

The main protease of SARS-CoV-2 cleaves histone deacetylases and DCP1A, attenuating the immune defense of the interferon-stimulated genes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019, constitutes an emerging human pathogen of zoonotic origin. A critical role in protecting the host against invading pathogens is carried out by interferon-stimulated genes (ISGs), the primary effectors of the type I interferon (IFN) response. All coronaviruses studied thus far have to first overcome the inhibitory effects of the IFN/ISG system before establishing efficient viral replication.

Diagnosis of nasopharyngeal carcinoma using an ultrasensitive immunoassay method based on nanoparticles.

The detection of the antibody of Epstein-Barr virus (EBV) is critical for the diagnosis of nasopharyngeal carcinoma (NPC). An accurate and scalable point-of-care detection method would support the screening, diagnosis, and monitoring of NPC patients. In this study, firstly, we made an antibody enrichment element, antigen-MNPs, which can screen out specific antibodies in a complex sample.

Construction of Genetically Encoded Biosensors to Monitor Subcellular Compartment-Specific Glutathione Response to Chemotherapeutic Drugs in Acute Myeloid Leukemia Cells.

Glutathione (GSH), the constituent of the redox buffer system, is a scavenger of reactive oxygen species (ROS), and its ratio to oxidized glutathione (GSSG) is a key indicator of oxidative stress in the cell. Acute myeloid leukemia (AML) is a highly aggressive hematopoietic malignancy characterized by aberrant levels of reduced and oxidized GSH due to oxidative stress. Therefore, the real-time, dynamic, and highly sensitive detection of GSH/GSSG in AML cells is of great interest for the clinical diagnosis and treatment of leukemia.

Dysregulation of Innate and Adaptive Immune Responses in Asymptomatic SARS-CoV-2 Infection with Delayed Viral Clearance.

Asymptomatic infection with SARS-CoV-2 is a major concern in the control of the COVID-19 pandemic. Many questions concerning asymptomatic infection remain to be answered, for example, what are the differences in infectivity and the immune response between asymptomatic and symptomatic infections? In this study, based on a cohort established by the Wuchang District Health Bureau of Wuhan in the early stage of the COVID-19 pandemic in Wuhan in 2019, we conducted a comprehensive analysis of the clinical, virological, immunological, and epidemiological data of asymptomatic infections. The major findings of this study included: 1) the asymptomatic cohort enrolled this study exhibited low-grade but recurrent activity of viral replication; 2) despite a lack of overt clinical symptoms, asymptomatic infections exhibited ongoing innate and adaptive immune responses; 3) however, the immune response from asymptomatic infections was not activated adequately, which may lead to delayed viral clearance.

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).

Optogenetic Control of Background Fluorescence Reduction for CRISPR-Based Genome Imaging.

The CRISPR/dCas9 system has become an essential tool for live-cell imaging of genomic loci, but it has limited applications in imaging low-/non-repetitive genomic loci due to the strong nuclear background noise emerging from many untargeted fluorescent modules. Here, we propose an optogenetically controlled background fluorescence reduction strategy that combines the CRISPR-SunTag system with a light-inducible nuclear export tag (LEXY). Utilizing the SunTag system, multiple copies of LEXY-tagged sfGFP were recruited to the C-terminal dCas9, recognizing the target genomic loci.

Tracking the Replication-Competent Zika Virus with Tetracysteine-Tagged Capsid Protein in Living Cells.

Real-time imaging of viruses in living cells considerably facilitates the study of virus-host interactions. However, generating a fluorescently labeled recombinant virus is challenging, especially for Zika virus (ZIKV), which causes microcephaly in neonates. The monocistronic nature of the ZIKV genome represents a major challenge for generating a replication-competent genetically engineered ZIKV suitable for real-time imaging.

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.

A switch-on molecular biosensor for detection of caspase-3 and imaging of apoptosis of cells.

Apoptosis is a form of programmed cell death that is essential for maintaining internal environmental stability. Disordered apoptosis can cause a variety of diseases; therefore, sensing apoptosis can provide help in study of mechanism of the relevant diseases and drug development. It is known that caspase-3 is a key enzyme involved in apoptosis and the expression of its activity is an indication of apoptosis.

Sustainability of SARS-CoV-2 Induced Humoral Immune Responses in COVID-19 Patients from Hospitalization to Convalescence Over Six Months.

Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection, the protection period of vaccination and the possibility of building an active herd immunity. This retrospective cohort study included 172 COVID-19 patients who were hospitalized in Wuhan. A total of 404 serum samples were obtained over six months from hospitalization to convalescence.

Illuminating single genomic loci in live cells by reducing nuclear background fluorescence.

The tagging of genomic loci in living cells provides visual evidence for the study of genomic spatial organization and gene interaction. CRISPR/dCas9 (clustered regularly interspaced short palindromic repeats/deactivated Cas9) labeling system labels genes through binding of the dCas9/sgRNA/fluorescent protein complex to repeat sequences in the target genomic loci. However, the existence of numerous fluorescent proteins in the nucleus usually causes a high background fluorescent readout.

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.

HIV-1 viral cores enter the nucleus collectively through the nuclear endocytosis-like pathway.

It is recognized that HIV-1 capsid cores are disassembled in the cytoplasm, releasing their genomes into the nucleus through nuclear pores, but there is also evidence showing the capsid (CA) exists in the nucleus. Whether HIV-1 enters the nucleus and how it enters the nucleus through the undersized nuclear pore remains mysterious. Based on multicolor labeling and real-time imaging of the viral and cellular components, our observations via light and electron microscopy suggest that HIV-1 selectively gathered at the microtubule organization center (MTOC), leading the nearby nuclear envelope (NE) to undergo deformation, invagination and restoration to form a nuclear vesicle in which the viral particles were wrapped; then, the inner membrane of the nuclear vesicle ruptured to release HIV-1 into the nucleus.

Enhanced Electrochemical Impedance Spectroscopy Analysis of Microbial Biofilms on an Electrochemically Generated Graphene Interface.

Biofilms can cause many bacterial diseases, such as dental disease. An detection of biofilms may help to screen antibiofilm drugs. An impedance measurement based on an Au electrode has been successfully used for real-time monitoring of animal and human cell growth.

Design and biosynthesis of functional protein nanostructures.

Proteins are one of the major classes of biomolecules that execute biological functions for maintenance of life. Various kinds of nanostructures self-assembled from proteins have been created in nature over millions of years of evolution, including protein nanowires, layers and nanocages. These protein nanostructures can be reconstructed and equipped with desired new functions.