Metagenomic sequencing combined with flow cytometry facilitated a novel microbial risk assessment framework for bacterial pathogens in municipal wastewater without cultivation.

A workflow that combined metagenomic sequencing with flow cytometry was developed. The absolute abundance of pathogens was accurately estimated in mock communities and real samples. Metagenome-assembled genomes binned from metagenomic data set is robust in phylogenetic analysis and virulence profiling.

Fe-Doped Carbon Dots as NIR-II Fluorescence Probe for In Vivo Gastric Imaging and pH Detection.

Carbon dots (CDs) with excellent cytocompatibility, tunable optical properties, and simple synthesis routes are highly desirable for use in optical bioimaging. However, the majority of existing CDs are triggered by ultraviolet/blue light, presenting emissions in the visible/first near-infrared (NIR-I) regions, which do not allow deep tissue penetration. Emerging research into CDs with NIR-II emission in the red region has generated limited designs with poor quantum yield, restricting their in vivo imaging applications due to low penetration depth.

Remote ischemic conditioning attenuates blood-brain barrier disruption after recombinant tissue plasminogen activator treatment via reducing PDGF-CC.

Treatment of acute ischemic stroke with the recombinant tissue plasminogen activator (rtPA) is associated with increased blood-brain barrier (BBB) disruption and hemorrhagic transformation. Remote ischemic conditioning (RIC) has demonstrated neuroprotective effects against acute ischemic stroke. However, whether and how RIC regulates rtPA-associated BBB disruption remains unclear.

Biomimetic Nanosonosensitizers Combined with Noninvasive Ultrasound Actuation to Reverse Drug Resistance and Sonodynamic-Enhanced Chemotherapy against Orthotopic Glioblastoma.

Glioblastoma (GBM) is the most devastating brain tumor and highly resistant to conventional chemotherapy. Herein, we introduce biomimetic nanosonosensitizer systems (MDNPs) combined with noninvasive ultrasound (US) actuation for orthotopic GBM-targeted delivery and sonodynamic-enhanced chemotherapy. MDNPs were fabricated with biodegradable and pH-sensitive polyglutamic acid (PGA) and the chemotherapeutic agent and sonosensitizer doxorubicin (DOX), camouflaged with human GBM U87 cell membranes.

Endplate volumetric bone mineral density biomechanically matched interbody cage.

Disc degenerative problems affect the aging population, globally, and interbody fusion is a crucial surgical treatment. The interbody cage is the critical implant in interbody fusion surgery; however, its subsidence risk becomes a remarkable clinical complication. Cage subsidence is caused due to a mismatch of material properties between the bone and implant, specifically, the higher elastic modulus of the cage relative to that of the spinal segments, inducing subsidence.

Histone Deacetylase Inhibitor Panobinostat Benefits the Therapeutic Efficacy of Oncolytic Herpes Simplex Virus Combined with PD-1/PD-L1 Blocking in Glioma and Squamous Cell Carcinoma Models.

Background: Combination therapy has been widely explored for oncolytic virus (OV), as it can be met with tumor resistance. The HDAC inhibitor (HDACi) panobinostat is a potent pan-deacetylase inhibitor which blocks multiple cancer-related pathways and reverses epigenetic events in cancer progression.

Methods: In this study, oncolytic activity in vitro and antitumor therapeutic efficacy in vivo when combined with oHSV and panobinostat were investigated.

Bioassay-Guided Isolation of Anthelmintic Components from , and the Mechanism of Action of Pharbitin.

Parasitic helminths continue to pose problems in human and veterinary medicine, as well as in agriculture. , the seeds of (Linn.) Choisy (Convolvulaceae), is a well-known traditional Chinese medicinal botanical preparation widely used for treating intestinal parasites in China owing to its desirable efficacy.

Radiotherapy Side Effects: Comprehensive Proteomic Study Unraveled Neural Stem Cell Degenerative Differentiation upon Ionizing Radiation.

Cranial radiation therapy is one of the most effective treatments for childhood brain cancers. Despite the ameliorated survival rate of juvenile patients, radiation exposure-induced brain neurogenic region injury could markedly impair patients' cognitive functions and even their quality of life. Determining the mechanism underlying neural stem cells (NSCs) response to irradiation stress is a crucial therapeutic strategy for cognitive impairment.

Tuning the arrangement of lamellar nanostructures: achieving the dual function of physically killing bacteria and promoting osteogenesis.

Bacteria killing behavior based on physical effects is preferred for biomedical implants because of the negligible associated side effects. However, our current understanding of the antibacterial activity of nanostructures remains limited and, in practice, nanoarchitectures that are created on orthopedics should also promote osteogenesis simultaneously. In this study, tilted and vertical nanolamellar structures are fabricated on semi-crystalline polyether-ether-ketone (PEEK) argon plasma treatment with or without pre-annealing.

Chondroitin Sulfate Targeting Nanodrug Achieves Near-Infrared Fluorescence-Guided Chemotherapy Against Triple-Negative Breast Primary and Lung Metastatic Cancer.

Introduction: Lack of highly expressed tumor target and ligands limits application of nano-medicine against triple-negative breast cancer (TNBC). Previous study reported that placenta-derived oncofetal chondroitin sulfate glycosaminoglycan chain (CSA) expressed on 90% of stage I-III invasive ductal breast carcinomas. Our study found the CSA anchor protein VAR2CSA derived small peptide plCSA had strong binding activity with TNBC cell lines and tumor tissue.

CAR-Macrophages and CAR-T Cells Synergistically Kill Tumor Cells In Vitro.

Chimeric antigen receptor (CAR)-expressing macrophages (CAR-M) have a great potential to improve cancer therapy, as shown from several recent preclinical studies. However, unlike CAR-T cell therapy, which has been widely studied, the efficacy and limitations of CAR-M cells remain to be established. To address this issue, in the present study, we compared three intracellular signaling domains (derived from common γ subunit of Fc receptors (FcRγ), multiple EGF-like-domains protein 10 (Megf10), and the CD19 cytoplasmic domain that recruits the p85 subunit of phosphoinositide-3 kinase (PI3K), respectively) for their ability to promote primary CAR-M functions, and investigated the potential synergistic effect between CAR-M and CAR-T cells in their ability to kill tumor cells.

Network Pharmacology and Molecular Docking Analysis Reveal Insights into the Molecular Mechanism of Shengma-Gegen Decoction on Monkeypox.

Background: A new viral outbreak caused by monkeypox has appeared after COVID-19. As of yet, no specific drug has been found for its treatment. Shengma-Gegen decoction (SMGGD), a pathogen-eliminating and detoxifying agent composed of four kinds of Chinese herbs, has been demonstrated to be effective against several viruses in China, suggesting that it may be effective in treating monkeypox, however, the precise role and mechanisms are still unknown.

Bifunctional Compounds as Molecular Degraders for Integrin-Facilitated Targeted Protein Degradation.

As effective ways to regulate protein levels, targeted protein degradation technologies have attracted great attention in recent years. Here, we established a novel integrin-facilitated lysosomal degradation (IFLD) strategy to degrade extracellular and cell membrane proteins using bifunctional compounds as molecular degraders. By conjugation of a target protein-binding ligand with an integrin-recognition ligand, the resulting molecular degrader proved to be highly efficient to induce the internalization and subsequent degradation of extracellular or cell membrane proteins in an integrin- and lysosome-dependent manner.

Role of small RNAs harbored by sperm in embryonic development and offspring phenotype.

Background: RNA harbored by mammalian sperm is increasingly considered to be an additional source of paternal hereditary information, beyond DNA. Recent studies have demonstrated the role of sperm small noncoding RNAs (sncRNAs) in modulating early embryonic development and offspring phenotype. The biogenesis of the sperm sRNA payload of mammalian sperm has been explored in many studies.

Extracellular vesicles from pristane-treated CD38-deficient mice express an anti-inflammatory neutrophil protein signature, which reflects the mild lupus severity elicited in these mice.

In CD38-deficient ( mice intraperitoneal injection of pristane induces a lupus-like disease, which is milder than that induced in WT mice, showing significant differences in the inflammatory and autoimmune processes triggered by pristane. Extracellular vesicles (EV) are present in all body fluids. Shed by cells, their molecular make-up reflects that of their cell of origin and/or tissue pathological situation.

Epigenetic mechanisms of Strip2 in differentiation of pluripotent stem cells.

Significant evidence points to Strip2 being a key regulator of the differentiation processes of pluripotent embryonic stem cells. However, Strip2 mediated epigenetic regulation of embryonic differentiation and development is quite unknown. Here, we identified several interaction partners of Strip2, importantly the co-repressor molecular protein complex nucleosome remodeling deacetylase/Tripartite motif-containing 28/Histone deacetylases/Histone-lysine N-methyltransferase SETDB1 (NuRD/TRIM28/HDACs/SETDB1) histone methyltransferase, which is primarily involved in regulation of the pluripotency of embryonic stem cells and its differentiation.

TRIM59 guards ER proteostasis and prevents Bortezomib-mediated colorectal cancer (CRC) cells' killing.

The endoplasmic reticulum (ER) is a critical organelle that preserves the protein homeostasis of cells. Under various stress conditions, cells evolve a degree of capacity to maintain ER proteostasis, which is usually augmented in tumor cells, including colorectal cancer (CRC) cells, to bolster their survival and resistance to apoptosis. Bortezomib (BTZ) is a promising drug used in CRC treatment; however, its main limitation result from drug resistance.

Evaluating Bacterial Pathogenesis Using a Model of Human Airway Organoids Infected with Pseudomonas aeruginosa Biofilms.

Pseudomonas aeruginosa is one of the leading invasive agents of human pulmonary infection, especially in patients with compromised immunity. Prior studies have used various models to establish P. aeruginosa infection and to analyze transcriptomic profiles of either the host or pathogen, and yet how much those works are relevant to the genuine human airway still raises doubts.

Fluorination Enhances NIR-II Emission and Photothermal Conversion Efficiency of Phototheranostic Agents for Imaging-Guided Cancer Therapy.

Phototheranostics with second near-infrared (NIR-II) imaging and photothermal effect have become a burgeoning biotechnology for tumor diagnosis and precise treatment. As important parameters of phototheranostic agents (PTAs), fluorescence quantum yield (QY) and photothermal conversion efficiency (PCE) are usually considered as a pair of contradictions that is difficult to be simultaneously enhanced. Herein, a fluorination strategy for designing A-D-A type PTAs with synchronously improved QY and PCE is proposed.

Reversibly Migratable Fluorescent Probe for Precise and Dynamic Evaluation of Cell Mitochondrial Membrane Potentials.

The mitochondrial membrane potential (MMP, ΔΨ) provides the charge gradient required for mitochondrial functions and is a key indicator of cellular health. The changes in MMP are closely related to diseases and the monitoring of MMP is thus vital for pathological study and drug development. However, most of the current fluorescent probes for MMP rely solely on the cell fluorescence intensity and are thus restricted by poor photostability, rendering them not suitable for long-term dynamic monitoring of MMP.

Oligostilbenes from the seeds of Paeonia lactiflora as potent GLP-1 secretagogues targeting TGR5 receptor.

One unusual stilbene trimer-flavonoid hybrid, paeonilactiflobenoid (1), together with six known stilbenes (2-7) were isolated from the seeds of Paeonia lactiflora. The structure of 1 was elucidated with the aid of HRESIMS, 1D and 2D NMR, [α] spectroscopic data and ECD calculation. Compounds 2-7 showed stimulative effects on GLP-1 secretion with promoting rates of 79.

Aggregation-Induced-Emission Photosensitizer-Loaded Nano-Superartificial Dendritic Cells with Directly Presenting Tumor Antigens and Reversed Immunosuppression for Photodynamically Boosted Immunotherapy.

The success of tumor immunotherapy highlights the potential of harnessing immune system to fight cancer. Activating both native T cells and exhausted T cells is a critical step for generating effective antitumor immunity, which is determined based on the efficient presentation of tumor antigens and co-stimulatory signals by antigen-presenting cells, as well as immunosuppressive reversal. However, strategies for achieving an efficient antigen presentation process and improving the immunosuppressive microenvironment remain unresolved.

A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants.

Population-based studies to identify disease-associated risk alleles typically require samples from a large number of individuals. Here, we report a human-induced pluripotent stem cell (hiPSC)-based screening strategy to link human genetics with viral infectivity. A genome-wide association study (GWAS) identified a cluster of single-nucleotide polymorphisms (SNPs) in a cis-regulatory region of the NDUFA4 gene, which was associated with susceptibility to Zika virus (ZIKV) infection.