In vitro nanomaterial testing: unveiling biases through biomolecular corona influence.

This article highlights the recent work of Castagnola, Armirotti, et al. (Nanoscale Horiz., 2024, https://doi.org/10.1039/D3NH00510K) on demonstrating that the widespread use of 10% fetal bovine serum in an in vitro assay cannot recapitulate the complexity of in vivo systemic administration.

Homozygous variant of MLC1 results in megalencephalic leukoencephalopathy with subcortical cysts.

BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare, inherited disorder that causes epilepsy, intellectual disorders, and early onset macrocephaly. MLC1 has been identified as a main pathogenic gene. METHODS: Clinical data such as magnetic resonance imaging (MRI), routine blood tests, and physical examinations were collected from proband. Trio whole-exome sequencing (WES) of the family was performed, and all variants with a minor allele frequency (<0.01) in the exon and canonical splicing sites were selected for further pathogenic evaluation. Candidate variants were validated using Sanger sequencing. RESULTS: Here, we report a new homozygous variant identified in two children from the same family in the MLC1 gene [NM_015166.4: c.838_843delinsATTTTA, (p.Ser280_Phe281delinsIleLeu)]. This variant is classified as variant of uncertain significance (VUS) according to the ACMG guidelines. Further experiments demonstrate that the newly identified variant causes a decrease of MLC1 protein levels when expressed in a heterologous expression system. CONCLUSION: Our case expands on this genetic variation and provides new evidence for the clinical diagnosis of MLC1-related MLC.

Double-side 2D/3D heterojunctions for inverted perovskite solar cells.

Defects at the top and bottom interfaces of three-dimensional (3D) perovskite photoabsorbers diminish the performance and operational stability of perovskite solar cells owing to charge recombination, ion migration and electric-field inhomogeneities1-5. Here we demonstrate that long alkyl amine ligands can generate near-phase-pure 2D perovskites at the top and bottom 3D perovskite interfaces and effectively resolve these issues. At the rear-contact side, we find that the alkyl amine ligand strengthens the interactions with the substrate through acid-base reactions with the phosphonic acid group from the organic hole-transporting self-assembled monolayer molecule, thus regulating the 2D perovskite formation. With this, inverted perovskite solar cells with double-side 2D/3D heterojunctions achieved a power conversion efficiency of 25.6% (certified 25.0%), retaining 95% of their initial power conversion efficiency after 1,000 h of 1-sun illumination at 85 °C in air.

Understanding the Impact of Sheep Digestion on Seed Germination in the Cold Desert Annual Diptychocarpus strictus with Emphasis on Fruit and Seed Heteromorphism.

This study aimed to investigate the morphological characteristics of fruits and seeds from Diptychocarpus strictus, a plant species inhabiting the cold desert pastoral area of China. Furthermore, this study sought to evaluate the germination potential of these seeds following digestion by sheep. This study employed the sheep rumen fistula method to simulate rumen digestion at various time intervals. Subsequently, an in vitro simulation method was utilized to simulate true gastric and intestinal digestion after rumen digestion. Paper germination tests were then conducted to assess the impact of the digestive process on the heteromorphic seed morphology and germination. During rumen digestion, the seeds were protected by wide wings. The results revealed a highly significant negative correlation (p < 0.01) between seed wing length and digestion time. Post-rumen digestion, variations in the germination rate among seeds from fruits at different locations were observed. Indicators, such as germination rate, exhibited a highly significant negative correlation with rumen digestion time (p < 0.01). In vitro simulated digestion tests demonstrated that Diptychocarpus strictus seeds retained their ability to germinate even after complete digestion within the livestock's digestive tract. The polymorphic nature of Diptychocarpus strictus seeds, coupled with their capacity to survive and germinate through the digestive tract, facilitates the spread of these seeds. This finding has implications for mitigating desert grassland degradation and promoting sustainable ecological development.

Development and Applications of D-Amino Acid Derivatives-based Metabolic Labeling of Bacterial Peptidoglycan.

Peptidoglycan, an essential component within the cell walls of virtually all bacteria, is composed of glycan strands linked by stem peptides that contain D-amino acids. The peptidoglycan biosynthesis machinery exhibits high tolerance to various D-amino acid derivatives. D-amino acid derivatives with different functionalities can thus be specifically incorporated into and label the peptidoglycan of bacteria, but not the host mammalian cells. This metabolic labeling strategy is highly selective, highly biocompatible, and broadly applicable, which has been utilized in various fields. This review introduces the metabolic labeling strategies of peptidoglycan by using D-amino acid derivatives, including one-step and two-step strategies. In addition, we emphasize the various applications of D-amino acid derivative-based metabolic labeling, including bacterial peptidoglycan visualization (existence, biosynthesis, and dynamics, etc.), bacterial visualization (including bacterial imaging and visualization of growth and division, metabolic activity, antibiotic susceptibility, etc.), pathogenic bacteria-targeted diagnostics and treatment (positron emission tomography (PET) imaging, photodynamic therapy, photothermal therapy, gas therapy, immunotherapy, etc.), and live bacteria-based therapy. Finally, a summary of this metabolic labeling and an outlook is provided.

HSPB6 Deficiency Promotes the Development of Aortic Dissection and Rupture.

To better understand the pathogenesis of acute type A aortic dissection, high-sensitivity liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS)-based proteomics and phosphoproteomics approaches were used to identify differential proteins. Heat shock protein family B (small) member 6 (HSPB6) in aortic dissection was significantly reduced in human and mouse aortic dissection samples by real-time PCR, western blotting, and immunohistochemical staining techniques. Using an HSPB6-knockout mouse, we investigated the potential role of HSPB6 in ß-aminopropionitrile monofumarate-induced aortic dissection. We found increased mortality and increased probability of ascending aortic dissection after HSPB6 knockout compared with wild-type mice. Mechanistically, our data suggest that HSPB6 deletion promoted vascular smooth muscle cell apoptosis. More importantly, HSPB6 deletion attenuated cofilin activity, leading to excessive smooth muscle cell stiffness and eventually resulting in the development of aortic dissection and rupture. Our data suggest that excessive stiffness of vascular smooth muscle cells caused by HSPB6 deficiency is a new pathogenetic mechanism leading to aortic dissection.

pH/GSH dual responsive nanosystem for nitric oxide generation enhanced type I photodynamic therapy.

Tumor hypoxia diminishes the effectiveness of traditional type II photodynamic therapy (PDT) due to oxygen consumption. Type I PDT, which can operate independently of oxygen, is a viable option for treating hypoxic tumors. In this study, we have designed and synthesized JSK@PEG-IR820 NPs that are responsive to the tumor microenvironment (TME) to enhance type I PDT through glutathione (GSH) depletion. Our approach aims to expand the sources of therapeutic benefits by promoting the generation of superoxide radicals (O2-.) while minimizing their consumption. The diisopropyl group within PEG-IR820 serves a dual purpose: it functions as a pH sensor for the disassembly of the NPs to release JSK and enhances intermolecular electron transfer to IR820, facilitating efficient O2-. generation. Simultaneously, the release of JSK leads to GSH depletion, resulting in the generation of nitric oxide (NO). This, in turn, contributes to the formation of highly cytotoxic peroxynitrite (ONOO-.), thereby enhancing the therapeutic efficacy of these NPs. NIR-II fluorescence imaging guided therapy has achieved successful tumor eradication with the assistance of laser therapy.

Oxygen-Independent Synchronized ROS Generation and Hypoxia Prodrug Activation with Z-Scheme Heterostructure Sonosensitizer.

Combination therapy has emerged as a promising approach for effective tumor treatment. However, the combination of sonodynamic therapy (SDT) and hypoxia-activated prodrugs (HAPs) has not been explored due to the contradictory requirement of oxygen (O2 ) for reactive oxygen species (ROS) generation and the necessity to avoid O2 for the activation of HAPs. In this study, this challenge is addressed by developing BiOCl-Au-Ag2 S Z-scheme heterostructure nanoparticles loaded with tirapazamine (TPZ) to achieve O2 -independent therapy. These nanoparticles demonstrate efficient electron-hole separation under ultrasound irradiation while maintaining a high redox potential. The generated holes react with water to efficiently produce hydroxyl radicals, while the electrons autonomously activate TPZ, negating the need for O2 . In vitro and in vivo assessments validate the effective tumor elimination by these Z-scheme nanoparticles without disrupting the hypoxic environment. This innovative design overcomes the limitations associated with O2 requirement in SDT and introduces a novel strategy for HAP activation and synergistic therapy between ROS and HAPs-based therapy.

Engineering Clinically Relevant Probiotics with Switchable "Nano-Promoter" and "Nano-Effector" for Precision Tumor Therapy.

Probiotics have the potential as biotherapeutic agents for cancer management in preclinical models and human trials by secreting antineoplastic or immunoregulatory agents in the tumor microenvironment (TME). However, current probiotics lack the ability to dynamically respond to unique TME characteristics, leading to limited therapeutic accuracy and efficacy. Although progress has been made in customizing controllable probiotics through synthetic biology, the engineering process is complex and the predictability of production is relatively low. To address this, here, for the first time, this work adopts pH-dependent peroxidase-like (POD-like) artificial enzymes as both an inducible "nano-promoter" and "nano-effector" to engineer clinically relevant probiotics to achieve switchable control of probiotic therapy. The nanozyme initially serves as an inducible "nano-promoter," generating trace amounts of nonlethal reactive oxygen species (ROS) stress to upregulate acidic metabolites in probiotics. Once metabolites acidify the TME to a threshold, the nanozyme switches to a "nano-effector," producing a great deal of lethal ROS to fight cancer. This approach shows promise in subcutaneous, orthotopic, and colitis-associated colorectal cancer tumors, offering a new methodology for modulating probiotic metabolism in a pathological environment.

The Landscape of Biomimetic Nanovesicles in Brain Diseases.

Brain diseases, such as brain tumors, neurodegenerative diseases, cerebrovascular diseases, and brain injuries, are caused by various pathophysiological changes, which pose a serious health threat. Brain disorders are often difficult to treat due to the presence of the blood-brain barrier (BBB). Biomimetic nanovesicles (BNVs), including endogenous extracellular vesicles (EVs) derived from various cells and artificial nanovesicles, possess the ability to penetrate the BBB and thus can be utilized for drug delivery to the brain. BNVs, especially endogenous EVs, are widely distributed in body fluids and usually carry various disease-related signal molecules such as proteins, RNA, and DNA, and may also be analyzed to understand the etiology and pathogenesis of brain diseases. This review covers the exhaustive classification and characterization of BNVs and pathophysiological roles involved in various brain diseases, and emphatically focuses on nanotechnology-integrated BNVs for brain disease theranostics, including various diagnosis strategies and precise therapeutic regulations (e.g., immunity regulation, disordered protein clearance, anti-neuroinflammation, neuroregeneration, angiogenesis, and the gut-brain axis regulation). The remaining challenges and future perspectives regarding the nanotechnology-integrated BNVs for the diagnosis and treatment of brain diseases are also discussed and outlined.

Fabrication of An Immunostimulatory Supramolecular Nanomedicine for Potent Cancer Chemoimmunotherapy.

Chemoimmunotherapy can boost strong antitumor immune responses by triggering immunogenic cell death (ICD), which highlights a promising prospect in clinical applications. However, current chemoimmunotherapy shows limited efficacy due to the low delivery efficiency and insufficient immunogenicity of available chemotherapeutic drugs. A supramolecular polymeric nanomedicine (Pt-Tu@NP) is herein reported using cucurbit[7]uril-based host-guest recognition and noncovalent self-assembly. Pt-Tu@NPs have excellent biodistribution and strongly evoke the endoplasmic reticulum stress-mediated ICD of tumor cells, triggering potent antitumor immune responses by promoting dendritic cell (DC) maturation and cytotoxic T cell infiltration. The coordinated butyrate promotes a positive feedback regulation between DCs and CD8+ T cells. Pt-Tu@NPs stimulate immune cold tumors into hot ones, working in synergy with an immune checkpoint blockade to effectively suppress tumor growth and metastasis, which suggests a promising approach for cancer chemoimmunotherapy.

Enhanced optoelectronic coupling for perovskite/silicon tandem solar cells.

Monolithic perovskite/silicon tandem solar cells are of great appeal as they promise high power conversion efficiencies (PCEs) at affordable cost. In state-of-the-art tandems, the perovskite top cell is electrically coupled to a silicon heterojunction bottom cell by means of a self-assembled monolayer (SAM), anchored on a transparent conductive oxide (TCO), which enables efficient charge transfer between the subcells1-3. Yet reproducible, high-performance tandem solar cells require energetically homogeneous SAM coverage, which remains challenging, especially on textured silicon bottom cells. Here, we resolve this issue by using ultrathin (5-nm) amorphous indium zinc oxide (IZO) as the interconnecting TCO, exploiting its high surface-potential homogeneity resulting from the absence of crystal grains and higher density of SAM anchoring sites when compared with commonly used crystalline TCOs. Combined with optical enhancements through equally thin IZO rear electrodes and improved front contact stacks, an independently certified PCE of 32.5% was obtained, which ranks among the highest for perovskite/silicon tandems. Our ultrathin transparent contact approach reduces indium consumption by approximately 80%, which is of importance to sustainable photovoltaics manufacturing4.

Anti-phagocytosis-blocking repolarization-resistant membrane-fusogenic liposome (ARMFUL) for adoptive cell immunotherapy.

Equipping multiple functionalities on adoptive effector cells is essential to overcome the complex immunological barriers in solid tumors for superior antitumor efficacy. However, current cell engineering technologies cannot endow these functionalities to cells within a single step because of the different spatial distributions of targets in one cell. Here, we present a core-shell anti-phagocytosis-blocking repolarization-resistant membrane-fusogenic liposome (ARMFUL) to achieve one-step multiplexing cell engineering for multifunctional cell construction. Through fusing with the M1 macrophage membrane, ARMFUL inserts an anti-CD47 (aCD47)-modified lipid shell onto the surface and simultaneously delivers colony-stimulating factor 1 receptor inhibitor BLZ945-loaded core into the cytoplasm. The surface-presenting aCD47 boosts macrophage's phagocytosis against the tumor by blocking CD47. The cytoplasm-located BLZ945 prompts its polarization resistance to M2 phenotype in the immunosuppressive microenvironment via inactivating the intracellular M2 polarization signaling pathway. This ARMFUL provides a versatile cell engineering platform to customize multimodal cellular functions for enhanced adoptive cell therapy.

Microenvironment-Activated Nanozyme-Armed Bacteriophages Efficiently Combat Bacterial Infection.

Bacterial infection is one of the greatest challenges to public health, requiring new therapeutic methods. Herein, an innovative nanozyme-armed phage (phage@palladium (Pd)) system is fabricated for combating bacterial infection. The proposed phage@Pd preserves the function of the phages to achieve precise recognition and adhesion to the host Escherichia coli. In aid of the phages, the ultrasmall Pd nanozymes equipped with conspicuous pH-dependent peroxidase-like activity can generate toxic hydroxyl radical around the bacteria in acidic and hydrogen-peroxide-overexpressed infection microenvironment while remaining inert in physiological conditions, thus realizing the noteworthy elimination of bacteria at infected sites, and in the meantime ensuring the biological safety of phage@Pd in healthy tissues. In addition, the filamentous structure of phage@Pd can also enhance its bactericidal efficiency toward nonhost bacteria by randomly entangling on them, indicating possible broad-spectrum germicidal efficacy. Notably, phage@Pd can not only eradicate planktonic bacteria, but also kill the bacteria inside the biofilm in vitro. For both in vivo models of acute bacterial pneumonia or subcutaneous abscess, phage@Pd shows significant activity in eliminating infection and promoting tissue recovery. These results demonstrate that the phage@Pd nanohybrid is a safe and effective antimicrobial agent, providing a new insight into development of advanced antibacterial materials.

Artificial-enzymes-armed Bifidobacterium longum probiotics for alleviating intestinal inflammation and microbiota dysbiosis.

Inflammatory bowel disease can be caused by the dysfunction of the intestinal mucosal barrier and dysregulation of gut microbiota. Traditional treatments use drugs to manage inflammation with possible probiotic therapy as an adjuvant. However, current standard practices often suffer from metabolic instability, limited targeting and result in unsatisfactory therapeutic outcomes. Here we report on artificial-enzyme-modified Bifidobacterium longum probiotics for reshaping a healthy immune system in inflammatory bowel disease. Probiotics can promote the targeting and retention of the biocompatible artificial enzymes to persistently scavenge elevated reactive oxygen species and alleviate inflammatory factors. The reduced inflammation caused by artificial enzymes improves bacterial viability to rapidly reshape the intestinal barrier functions and restore the gut microbiota. The therapeutic effects are demonstrated in murine and canine models and show superior outcomes to traditional clinical drugs.

Mace-Like Plasmonic Au-Pd Heterostructures Boost Near-Infrared Photoimmunotherapy.

Photoimmunotherapy, with spatiotemporal precision and noninvasive property, has provided a novel targeted therapeutic strategy for highly malignant triple-negative breast cancer (TNBC). However, their therapeutic effect is severely restricted by the insufficient generation of tumor antigens and the weak activation of immune response, which is caused by the limited tissue penetration of light and complex immunosuppressive microenvironment. To improve the outcomes, herein, mace-like plasmonic AuPd heterostructures (Au Pd HSs) have been fabricated to boost near-infrared (NIR) photoimmunotherapy. The plasmonic Au Pd HSs exhibit strong photothermal and photodynamic effects under NIR light irradiation, effectively triggering immunogenic cell death (ICD) to activate the immune response. Meanwhile, the spiky surface of Au Pd HSs can also stimulate the maturation of DCs to present these antigens, amplifying the immune response. Ultimately, combining with anti-programmed death-ligand 1 (α-PD-L1) will further reverse the immunosuppressive microenvironment and enhance the infiltration of cytotoxic T lymphocytes (CTLs), not only eradicating primary TNBC but also completely inhibiting mimetic metastatic TNBC. Overall, the current study opens a new path for the treatment of TNBC through immunotherapy by integrating nanotopology and plasmonic performance.

Quantifying Concentrations and Emissions of Hexachlorobutadiene - A New Atmospheric Persistent Organic Pollutant in northern China.

Hexachlorobutadiene (HCBD) was listed as a new persistent organic pollutant for global regulation under Stockholm Convention in 2015, and there has been scarce information on its atmospheric concentrations, distributions, and emission sources. HCBD air samples were collected and analyzed to characterize concentrations and distributions at high elevation and urban sites as well as emission source locations in Northern China. We found ambient concentrations of HCBD in Northern China averaged at 34 ± 16 and 36 ± 28 pptv at urban sites in Jinan and Tai'an, respectively, and 31 ± 21 pptv at a high-elevation site Mount Tai. HCBD concentrations at the high elevation and urban sites were found to be affected by long-range transport under the influence of the East Asian monsoon climate. Over potential sources areas, we found concentrations of 76 ± 33 pptv in a mixed factory park, 59 ± 21 pptv in a rubber plant and 74 ± 8 pptv in a municipal solid waste (MSW) landfill area, which were all several times higher than in urban sites. The large concentration gradient across the various environments revealed strong emission sources of HCBD, especially over MSW landfill and Cl-compound production and application areas. An emission rate of 9.2 × 104 kg/yr and an oxidation rate of 32.9 kg/yr for HCBD were estimated for the mixed factory park. OH and Cl are much more active in reaction with HCBD than other oxidants in the atmosphere. Dry deposition and oxidation removed about 5.3% and 0.04%, respectively, of the emitted, suggesting that ∼95% of the emitted HCBD remaining in the atmosphere and could be transported for redistribution. Our findings revealed significant emission sources of HCBD in northern China, which was in turn affected by major sources in East-central China. The regional influence of HCBD pollution warrants serious concerns and points to the need to develop mitigation strategies.

Endoscopic Ischial Tuberosity Osteophyte Resection for Treatment of Ischiofemoral Impingement: A Case Report.

ABSTRACT: Ischiofemoral impingement is a distinct pathologic finding with abnormal osseous contact between the ischium and the lesser trochanter of the femur. Lesser trochanter excision has been recommended for recalcitrant ischiofemoral impingement through an open or endoscopic approach; however, no study has included ischial tuberosity osteophyte resection and refixation of the hamstring tendon. We report an endoscopic procedure involving ischial tuberosity osteophyte resection with refixation of the partially detached hamstring insertion through a posterior approach in the prone position. Using this technique, it is easier to reach the lesion and less likely to injure the sciatic nerve. The postoperative pain score (visual analogy score) was significantly decreased, the modified Harris hip score increased from 39 preoperatively to 86 postoperatively, and there was no adverse effect on the hamstring tendon.

Self-Adaptive Single-Atom Catalyst Boosting Selective Ferroptosis in Tumor Cells.

Ferroptosis, resulting from the catastrophic accumulation of lipid reactive oxygen species (ROS) and the inactivation of glutathione (GSH)-dependent peroxidase 4 (GPX4), has emerged as a form of regulated cell death for cancer therapy. Despite progress made with current ferroptosis inducers, efficient systems to trigger ferroptosis remain challenging, owing largely to their low activity, uncontrollable behavior, and even nonselective interactions. Here, we report a self-adaptive ferroptosis platform by engineering a DNA modulator onto the surface of single-atom nanozymes (SAzymes). The modulator could not only specifically intensify the ROS-generating activity but also endow the SAzymes with on-demand GSH-consuming ability in tumor cells, accelerating selective and safe ferroptosis. The self-adaptive antitumor response has been demonstrated in colon cancer and breast cancer, promoting the development of selective cancer therapy.