Biomaterial Surface-Mediated Macrophages Exert Immunomodulatory Roles by Exosomal CCL2-Induced Membrane Integrin β1 Trafficking in Recipient Cells.

The interaction between biomaterials and immune system is a critical area of research, especially in tissue engineering and regenerative medicine. A fascinating and less explored aspect involves the immunomodulatory behaviors of macrophage (MΦ)-derived exosomes induced by biomaterial surfaces. Herein, untreated surface, nanostructured surface, and type I collagen (Col-I)-decorated nanostructured surface of titanium implants are chosen to culture MΦs, followed by extraction of MΦ-derived exosomes and investigation of their immunomodulatory functions and mechanisms.

Glut3 overexpression improves environmental glucose uptake and antitumor efficacy of CAR-T cells in solid tumors.

Background: Glucose deprivation inhibits T-cell metabolism and function. Glucose levels are low in the tumor microenvironment of solid tumors and insufficient glucose uptake limits the antitumor response of T cells. Furthermore, glucose restriction can contribute to the failure of chimeric antigen receptor T (CAR-T) cell therapy for solid tumors.

Construction and high-throughput screening of gradient nanowire coatings on titanium surface towards ameliorated osseointegration.

Surface nano-modification has emerged as an effective strategy to enhance osseointegration of titanium (Ti) implants. Despite its promise, rational optimization of surface nanomorphology for ameliorated osseointegration remains a significant challenge. Our research pioneering developed a one-step alkali etching technique to produce a gradient nanowire coating with continuously varied dimensions on Ti surfaces, which was subsequently served as a versatile platform for high-throughput screening of optimal dimensions to enhance osseointegration.

Relationship between thyroid-stimulating hormone and blood lipids in patients with first-episode depression.

Background: Previous studies demonstrated thyroid stimulating hormone (TSH) plays an important role in regulating lipid metabolism, but the relationship between the two is controversial. Meanwhile, it has not been reported in a population with major depressive disorder (MDD).

Methods: We divided 1718 first-episode and drug naïve patients with MDD into a TSH abnormal group (TSH-AB) and a TSH normal group (TSH-NOR).

CAR T Cells Engineered to Secrete IFNκ Induce Tumor Ferroptosis via an IFNAR/STAT1/ACSL4 Axis.

Ferroptosis is an iron-dependent form of cell death that influences cancer immunity. Therapeutic modulation of ferroptosis is considered a potential strategy to enhance the efficacy of other cancer therapies, including immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy. In this study, we demonstrated that IFNκ influenced the induction of ferroptosis.

Astroglial morphological changes in periaqueductal grey in different pain and itch mice models.

Background: The periaqueductal gray (PAG) plays a well-established pivotal role in the descending pain modulatory circuit. The objective of this study was to investigate morphological changes in the astroglia in models that are commonly used in pain and itch studies.

Methods: Five different mouse models of pain, as well as two models of chronic itch, were established using complete Freund's adjuvant (CFA), spared nerve injury (SNI), bone cancer pain (BCP), cisplatin (CIS), and paclitaxel (PTX) for pain, and diphenylcyclopropenone (DCP) and acetone and diethyl ether followed by water (AEW) for chronic itch.

Dynamic regulation of phosphorylation of NMDA receptor GluN2B subunit tyrosine residues mediates ketamine rapid antidepressant effects.

The rapid antidepressant effects of ketamine depend on the N-methyl-D-aspartate (NMDA) receptor containing 2B subunit (NR2B), whose function is influenced by its phosphorylated regulation and distribution within and outside synapses. It remains unclear if ketamine's rapid onset of antidepressant effects relies on the dynamic phosphorylated regulation of NR2B within and outside synapses. Here, we show that ketamine rapidlyalleviated depression-like behaviors and normalized abnormal expression of pTyrNR2B and striatal-enriched protein tyrosine phosphatase (STEP) 61 within and outside synapses in the medial prefrontal cortex (mPFC) induced by chronic unpredictable stress (CUS) and conditional knockdown of STEP 61, a key phosphatase of NR2B, within 1 hour after administration Together, our results delineate the rapid initiation of ketamine's antidepressant effects results from the restoration of NR2B phosphorylation homeostasis within and outside synapses.

Targeting metabolism to improve CAR-T cells therapeutic efficacy.

Chimeric antigen receptor T (CAR-T) cell therapy achieved advanced progress in the treatment of hematological tumors. However, the application of CAR-T cell therapy for solid tumors still faces many challenges. Competition with tumor cells for metabolic resources in an already nutrient-poor tumor microenvironment is a major contributing cause to CAR-T cell therapy's low effectiveness.

Effectiveness and safety of second-generation antipsychotics for psychiatric disorders apart from schizophrenia: A systematic review and meta-analysis.

Second-generation antipsychotics (SGAs) are widely used in treating schizophrenia and related disorders, also other mental disorders. However, the efficacy and safety of SGAs for treating other mental disorders is unclear. A systematic literature search for randomized, placebo-controlled trials of 11 SGAs for treating 18 mental disorders apart from schizophrenia were carried out from database inception to April 3, 2022.

Large-scale pathway reconstruction and colorimetric screening accelerate cellular metabolism engineering.

The capability to manipulate and analyze hard-wired metabolic pathways sets the pace at which we can engineer cellular metabolism. Here, we present a framework to extensively rewrite the central metabolic pathway for malonyl-CoA biosynthesis in yeast and readily assess malonyl-CoA output based on pathway-scale DNA reconstruction in combination with colorimetric screening (Pracs). We applied Pracs to generate and test millions of enzyme variants by introducing genetic mutations into the whole set of genes encoding the malonyl-CoA biosynthetic pathway and identified hundreds of beneficial enzyme mutants with increased malonyl-CoA output.

Budesonide-liposomes inclusion complex in thermosensitive gel alleviates DSS-induced ulcerative colitis in mice.

Purpose: A novel formulation for Ulcerative Colitis (UC) treatment by rectal administration with budesonide liposomes (Bud ) and thermosensitive gel (Gel) was developed for future clinical use. To evaluate the anti-inflammatory activity and colon mucosal protection of this novel formulation compared with the other three in mice.

Methods: Bud was prepared by reverse evaporation method and then dispersed in solutions with PL407 and PL188 by a cold method.

An EIT image reconstruction method based on DenseNet with multi-scale convolution.

Electrical impedance tomography (EIT) is an imaging technique that non-invasively acquires the electrical conductivity distribution within a field. The ill-posed and nonlinear nature of the image reconstruction process results in lower quality of the obtained images. To solve this problem, an EIT image reconstruction method based on DenseNet with multi-scale convolution named MS-DenseNet is proposed.

An Anisotropic Hydrogel by Programmable Ionic Crosslinking for Sequential Two-Stage Actuation under Single Stimulus.

As one of the most important anisotropic intelligent materials, bi-layer stimuli-responsive actuating hydrogels have proven their wide potential in soft robots, artificial muscles, biosensors, and drug delivery. However, they can commonly provide a simple one-actuating process under one external stimulus, which severely limits their further application. Herein, we have developed a new anisotropic hydrogel actuator by local ionic crosslinking on the poly(acrylic acid) (PAA) hydrogel layer of the bi-layer hydrogel for sequential two-stage bending under a single stimulus.

The role of nanopores constructed on the micropitted titanium surface in the immune responses of macrophages and the potential mechanisms.

The delayed transition of macrophages (MΦs) from pro-inflammatory M1 to the pro-healing M2 state on implant surfaces is one of the most important reasons for poor osseointegration. This work reports the construction of closely packed nanopores with a small diameter on the micropitted titanium (Ti) surface by two-step acid etching to promote the M1-to-M2 transition of MΦs and pays special attention to the potential mechanisms by which the nanopores decorating the micropits exert immunomodulatory effects. The results show that the structure composed of hybrid nanopores (10-25 nm) and micropits (5-15 μm) can be produced on the Ti surface by a two-step acid etching process.

Type I collagen decorated nanoporous network on titanium implant surface promotes osseointegration through mediating immunomodulation, angiogenesis, and osteogenesis.

Osseointegration of implants is a complex physiological process that requires temporal and spatial regulation of immune responses, angiogenesis, and osteogenesis. To achieve efficient and long-term osseointegration, type I collagen (COL1) decorated nanoporous network was developed on titanium substrates via alkali treatment, polydopamine coating, and layer-by-layer (LBL) self-assembly. It was noted that the simple physisorbed COL1 could be easily desorbed from the nanostructured surface, however, multilayer COL1 constructed by polydopamine and LBL self-assembly obscured the nanoporous network of the alkali-treated titanium surfaces.

Fabrication and characterization of biodegradable Zn scaffold by vacuum heating-press sintering for bone repair.

Bone repair materials with excellent mechanical properties are highly desirable, especially in load-bearing sits. However, the currently used ceramic- and polymer-based ones mainly show poor mechanical properties. Recently, biodegradable metals have attracted extensive attention due to their reliable mechanical strength and degradability.

Biocompatible silane adhesion layer on titanium implants improves angiogenesis and osteogenesis.

Silane adhesion layer strategy has been widely used to covalently graft biomolecules to the titanium implant surface, thereby conferring the implant bioactivity to ameliorate osseointegration. However, few researchers pay attention to the effects of silanization parameters on biocompatibility and biofunctionality of the silane adhesion layers. Accordingly, the present study successfully fabricated the silane adhesion layers with different thickness, intactness, and surface morphologies by introducing 3-aminopropyltriethoxysilane on the alkali-treated titanium surface in time-varied processing of silanization.

Resveratrol promotes osteogenesis and angiogenesis through mediating immunology of senescent macrophages.

Orthopedic implants have been used clinically to restore the functions of the compromised bone tissues, but there is still a relatively high risk of failure for elderly people. A critical reason is pro-inflammatory immune microenvironment created by senescent macrophages with homeostasis imbalance impairs osteogenesis and angiogenesis, two major processes involved in implant osseointegration. The present work proposes to use resveratrol as an autophagy inducing agent to upregulate the autophagy level of senescent macrophages to restore homeostasis, consequently generating a favorable immune microenvironment.

Exosomes derived from magnesium ion-stimulated macrophages inhibit angiogenesis.

Angiogenesis, an essential prerequisite to osteogenesis in bone repair and regeneration, can be mediated by immunoregulation of macrophages. Magnesium and its alloys are promising biodegradable bone implant materials and can affect immunoregulation of macrophages by the degradation products (magnesium ions). Nevertheless, the mechanism of macrophage-derived exosomes stimulated by Mg ions in immunoregulation is still not well understood.

Engineering and functional analysis of yeast with a monotypic 40S ribosome subunit.

Emerging evidence reveals that ribosomes are not monolithic but dynamic machines with heterogeneous protein compositions that can reshape ribosomal translational abilities and cellular adaptation to environmental changes. Duplications of ribosomal protein (RP) genes are ubiquitous among organisms and are believed to affect cell function through paralog-specific regulation (e.g.

Exosomes derived from macrophages upon Zn ion stimulation promote osteoblast and endothelial cell functions.

Osteogenesis and angiogenesis are both important for implant osseointegration, which can be tailored by immunomodulation of macrophages. Zn, a novel biodegradable material, can modulate macrophage functions in its ionic form. However, whether macrophage-derived exosomes, novel carriers of intracellular communication, participate in the process is still unclear.

Exosomes derived from macrophages upon cobalt ion stimulation promote angiogenesis.

Angiogenesis is critical for tissue repair and regeneration, including implant osseointegration. It is well known that macrophages exert immunomodulatory functions in angiogenesis. However, whether macrophage-derived exosomes participate in the process is still unclear.