Discovery and preclinical evaluation of BPB-101: a novel triple functional bispecific antibody targeting GARP-TGF-β complex/SLC, free TGF-β and PD-L1.

Background: In the tumor microenvironment (TME), the transforming growth factor-β (TGF-β) and programmed cell death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling axes are complementary, nonredundant immunosuppressive signaling pathways. Studies have revealed that active TGF-β is mainly released from the glycoprotein A repetitions predominant (GARP)-TGF-β complex on the surface of activated regulatory T cells (Tregs), B cells, natural killer (NK) cells, and tumor cells. The currently available antibodies or fusion proteins that target TGF-β are limited in their abilities to simultaneously block TGF-β release and neutralize active TGF-β in the TME, thus limiting their antitumor effects.

Signal peptidase SpsB coordinates staphylococcal cell cycle, surface protein septal trafficking and LTA synthesis.

Many cell wall anchored surface proteins of Gram-positive bacteria harbor a highly conserved YSIRK/G-S signal peptide (SP), which deposits surface protein precursors at the cell division septum where they are subsequently anchored to septal peptidoglycan. Previously we identified that LtaS-mediated lipoteichoic acid (LTA) synthesis regulates septal trafficking of YSIRK+ proteins in . Interestingly, both LtaS and SP are cleaved by the signal peptidase SpsB, but the biological implications remain unclear.

Compact polarization transceiver module for fiber optic gyroscopes.

This paper reports a transceiver module with a high polarization extinction ratio (PER) for the polarization-maintaining interferometric fiber optic gyroscope (PM-IFOG). This transceiver utilizes a graded-index lens featuring a slanted face coated with a multilayer film, enabling simultaneous collimation and beam splitting. Configurations of the graded-index splitter lens and the corresponding transceiver module are simulated and designed using the ray matrix method and physical optical propagation.

Dynamic Nature of Type I Signal Peptidases.

Molecular dynamics simulations are used to interrogate the dynamic nature of Type I signal peptidases, SpsA and SpsB, including the impact of the P29S mutation of SpsB. Fluctuations and plasticity- rigidity characteristics vary among the proteins, particularly in the extracellular domain. Intriguingly, the P29S mutation, which influences susceptibility to arylomycin antibiotics, affect the mechanically coupled motions in SpsB.

The inaugural Junior Editorial Board-lessons learned and the path forward toward improving the peer review process.

The inaugural Junior Editorial Board (JEB) of consisted of 64 early-career researchers active from 2022 to 2023. The goal of the JEB was to train early-career researchers in the art of peer review under the guidance of experienced editors. JEB members gained hands-on experience in peer review by participating in modules detailing the publishing process through the lenses of the journal, editor, and reviewer.

Why should early-career scientists publish in society journals.

In this editorial, written by early-career scientists, we advocate for the invaluable role of society journals in our scientific community. By choosing to support these journals as authors, peer reviewers, and as editors, we can reinforce our academic growth and benefit from their re-investment back into the scientific ecosystem. Considering the numerous clear merits of this system for future generations of microbiologists and more broadly, society, we argue that early-career researchers should publish our high-quality research in society journals to shape the future of science and scientific publishing landscape.

Intercellular Molecular Crosstalk Networks within Invasive and Immunosuppressive Tumor Microenvironment Subtypes Associated with Clinical Outcomes in Four Cancer Types.

Heterogeneity is a critical basis for understanding how the tumor microenvironment (TME) contributes to tumor progression. However, an understanding of the specific characteristics and functions of TME subtypes (subTMEs) in the progression of cancer is required for further investigations into single-cell resolutions. Here, we analyzed single-cell RNA sequencing data of 250 clinical samples with more than 200,000 cells analyzed in each cancer datum.

Tracking Cell Wall-Anchored Proteins in Gram-Positive Bacteria.

Cell wall-anchored surface proteins are integral components of Gram-positive bacterial cell envelope and vital for bacterial survival in different environmental niches. To fulfill their functions, surface protein precursors translocate from cytoplasm to bacterial cell surface in three sequential steps: secretion across the cytoplasmic membrane, covalently anchoring to the cell wall precursor lipid II by sortase A, and incorporation of the lipid II-linked precursors into mature cell wall peptidoglycan. Here, we describe a series of immunofluorescence microscopy methods to track the subcellular localization of cell wall-anchored proteins along the sorting pathway.

The identification of two M20B family peptidases required for full virulence in .

We have previously demonstrated that deletion of an intracellular leucine aminopeptidase results in attenuated virulence of . Herein we explore the role of 10 other aminopeptidases in pathogenesis. Using a human blood survival assay we identified mutations in two enzymes from the M20B family (PepT1 and PepT2) as having markedly decreased survival compared to the parent.

Bilateral insufficiency fracture of coracoid process: A rare case report.

A 69-year-old man was admitted to the hospital for a left femoral neck fracture. A preliminary chest computed tomography scan showed no coracoid process fracture. The patient had no history of trauma during his hospitalization.

Single-cell and spatial analyses reveal the association between gene expression of glutamine synthetase with the immunosuppressive phenotype of APOE+CTSZ+TAM in cancers.

An immunosuppressive state is regulated by various factors in the tumor microenvironment (TME), including, but not limited to, metabolic plasticity of immunosuppressive cells and cytokines secreted by these cells. We used single-cell RNA-sequencing (scRNA-seq) data and applied single-cell flux estimation analysis to characterize the link between metabolism and cellular function within the hypoxic TME of colorectal (CRC) and lung cancer. In terms of metabolic heterogeneity, we found myeloid cells potentially inclined to accumulate glutamine but tumor cells inclined to accumulate glutamate.

Dual function of anti-biofilm and modulating biofilm equilibrium of orthodontic cement containing quaternary ammonium salt.

The objectives of this study were to incorporate dimethylaminohexadecyl methacrylate (DMAHDM) into resin-modified glass ionomer cement (RMGI) to develop a novel orthodontic cement which endowed RMGI with strong antibacterial ability and investigated its modulation biofilm equilibrium from cariogenic state to non-cariogenic state for the first time. Cariogenic Streptococcus mutans (S. mutans), and non-cariogenic Streptococcus sanguinis (S.

Novel protein-repellent and antibacterial polymethyl methacrylate dental resin in water-aging for 6 months.

Background: The present study aimed to develop a novel protein-repellent and antibacterial polymethyl methacrylate (PMMA) dental resin with 2-methacryloyloxyethyl phosphorylcholine (MPC) and quaternary ammonium dimethylaminohexadecyl methacrylate (DMAHDM), and to investigate the effects of water-aging for 6 months on the mechanical properties, protein adsorption, and antibacterial activity of the dental resin.

Methods: Four groups were tested: PMMA control; PMMA + 3% MPC; PMMA + 1.5% DMAHDM; and PMMA + 3% MPC + 1.

Directly modulated azimuthally polarized vector beam laser design.

Directly modulated vector beam lasers are increasingly desirable for wide applications ranging from optical manipulation to optical communications. We report the first, to our knowledge, high-speed directly modulated vector beam laser with azimuthally polarized emission. It is a microcylinder cavity interacted with a proper second-order grating on top, which enables single mode lasing and efficient surface emission.

Dual-responsive nanoparticles with transformable shape and reversible charge for amplified chemo-photodynamic therapy of breast cancer.

Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention, which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6 (Ce6), hydrophilic chemotherapeutic drug berberrubine (BBR) and matrix metalloproteinase-2 (MMP-2) response peptide (PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6 (BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine (PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time.

Intelligent lesion blood-brain barrier targeting nano-missiles for Alzheimer's disease treatment by anti-neuroinflammation and neuroprotection.

The treatment of Alzheimer's disease (AD) is one of the most difficult challenges in neurodegenerative diseases due to the insufficient blood‒brain barrier (BBB) permeability and unsatisfactory intra-brain distribution of drugs. Therefore, we established an ibuprofen and FK506 encapsulated drug co-delivery system (Ibu&FK@RNPs), which can target the receptor of advanced glycation endproducts (RAGE) and response to the high level of reactive oxygen species (ROS) in AD. RAGE is highly and specifically expressed on the lesion neurovascular unit of AD, this property helps to improve targeting specificity of the system and reduce unselective distribution in normal brain.

Glymphatic System and Subsidiary Pathways Drive Nanoparticles Away from the Brain.

Although drug delivery systems (DDS) are efficient in brain delivery, they face failure in clinical settings due to their potential toxicity to the central nervous system. Little is known about where the DDS will go after brain delivery, and no specific elimination route that shares a passage with DDS has been verified. Hence, identifying harmless DDS for brain delivery and determining their fate there would strongly contribute to their clinical translation.

Acid-Responsive Dual-Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder.

The treatment of autism spectrum disorder (ASD) is one of the most difficult challenges in neurodevelopmental diseases, because of the unclear pathogenesis research and low brain-lesion targeting efficiency. Besides, maternal immune activation has been reported as the most mature and widely used model of ASD and aspirin-triggered lipoxin A4 is a potent anti-inflammatory mediator being involved in the resolution of neuroinflammation in ASD. Therefore, an aspirin encapsulated cascade drug delivery system (Asp@TMNPs) is established, which can successively target the blood-brain barrier (BBB) and microglial cells and response to the acid microenvironment in lysosome.

Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis.

Solid tumors always exhibit local hypoxia, resulting in the high metastasis and inertness to chemotherapy. Reconstruction of hypoxic tumor microenvironment (TME) is considered a potential therapy compared to directly killing tumor cells. However, the insufficient oxygen delivery to deep tumor and the confronting "Warburg effect" compromise the efficacy of hypoxia alleviation.

Advances of nanomedicines in breast cancer metastasis treatment targeting different metastatic stages.

Breast cancer is the most common tumor in women, and the metastasis further increases the malignancy with extremely high mortality. However, there is almost no effective method in the clinic to completely inhibit breast cancer metastasis due to the dynamic multistep process with complex pathways and scattered occurring site. Nowadays, nanomedicines have been evidenced with great potential in treating cancer metastasis.

Tracking the Subcellular Localization of Surface Proteins in by Immunofluorescence Microscopy.

Surface proteins of and other Gram-positive bacteria play essential roles in bacterial colonization and host-microbe interactions. Surface protein precursors containing a YSIRK/GXXS signal peptide are translocated across the septal membrane at mid-cell, anchored to the cell wall peptidoglycan at the cross-wall compartment, and presented on the new hemispheres of the daughter cells following cell division. After several generations of cell division, these surface proteins will eventually cover the entire cell surface.

Spatial regulation of protein A in Staphylococcus aureus.

Surface proteins of Staphylococcus aureus play vital roles in bacterial physiology and pathogenesis. Recent work suggests that surface proteins are spatially regulated by a YSIRK/GXXS signal peptide that promotes cross-wall targeting at the mid-cell, though the mechanisms remain unclear. We previously showed that protein A (SpA), a YSIRK/GXXS protein and key staphylococcal virulence factor, mis-localizes in a ltaS mutant deficient in lipoteichoic acid (LTA) production.

The effect of remote ischemic postconditioning on autonomic function in patients with acute ischemic stroke: A Randomized Controlled Trail.

Objective: The evidence for the effect of remote ischemic postconditioning(RIpostC) on autonomic function in patients with acute ischemic stroke(AIS) is lacking and the neural mechanism underlying the protection of RIpostC remains speculative. This trial was aimed to evaluated the efficiency of RIpostC on autonomic function in AIS patients.

Design: One hundred and six AIS patients were included in this prospective, randomized, placebo-controlled trial.

Ultra-Wideband RCS Reduction Based on Non-Planar Coding Diffusive Metasurface.

A novel non-planar coding metasurface optimized by discrete particle swarm algorithm (DPSO) is proposed in terms of the property of wideband radar cross-section (RCS) and diffuse scattering. The design consists of two unit cells, "0" and "1", which have a 180° ± 37° phase difference for phase interference cancellation. The 10 dB monostatic RCS reduction frequency range of the metasurface is from 6.