Analysis of the Nonequilibrium Phase Change Behaviors of the Cryoprotectant Solutions for Cryopreservation of Human Red Blood Cells with Low-Concentration Glycerol.

Recently, we proposed a low-glycerol cryoprotectant formulation (consisting of 0.4 M trehalose and 5% glycerol) for cryopreservation of human red blood cells (RBCs), which greatly reduced the concentration of glycerol, minimized intracellular ice damage, and achieved high recovery. Although this study was successful in cellular experiments, the nonequilibrium phase transition behaviors of the cryoprotective agent solution have not been systematically analyzed. Therefore, it is essential to provide reliable thermodynamic data to substantiate the viability of this cryopreservation technique. In this study, the phase change behaviors and thermal properties of typical trehalose and/or glycerol solutions quenched in liquid nitrogen were investigated using differential scanning calorimetry and cryomicroscopy. It was found that the glass transition temperatures of both the trehalose aqueous solution (<1.0 M) and glycerol aqueous solution (<40% w/v) did not vary apparently with the concentration at low concentrations, while they increased significantly with increasing concentration at high concentrations. Moreover, it was revealed that the inhibitory effect of trehalose on ice growth was affected by glycerol. We further found that the addition of low concentrations of glycerol facilitates the partial glass transition of trehalose solutions at low concentrations. The results of this work provide reliable thermodynamic data to support the cryopreservation of human RBCs with unusually low concentrations of glycerol.

Chitosan-based food-grade Pickering emulsion loading with Rosa roxburghii extract against precancerous lesions of gastric carcinoma.

Precancerous lesions of gastric carcinoma (PLGC) are the most important stage in the development of gastric cancer, accompanied by significant oxidative stress and inflammatory response. Rosa roxburghii extract (RRE) has unique advantages in anti-PLGC due to its multi-component, high antioxidant and anti-inflammatory activities. However, the astringency and instability of RRE in the digestive tract seriously hinder its clinical application. Herein, we report a chitosan-based food-grade Pickering emulsion (PE) for loading RRE to block unpleasant taste, improve stability, and promote the entry of RRE into gastric epithelial cells through the gastric adhesion of chitosan, thereby enhancing preventive and therapeutic effects against PLGC. This Pickering emulsion is constructed as a water-in-oil (W/O) emulsion stabilized by the food-grade nanoparticles composed of soybean protein isolate (SPI) and chitosan (CS) through electrostatic interaction (defined as RRE@PE). The experimental results showed that RRE@PE performed better efficacy against PLGC than RRE by scavenging or inhibiting reactive oxygen species generation and reducing inflammatory cytokines. This Pickering emulsion enhances the application potential of RRE and is expected to be used for the treatment of clinical patients with PLGC.

Size-exclusion chromatography-based extracellular vesicle size subtyping and multiplex membrane protein profiling for differentiating gastrointestinal cancer prognosis.

Extracellular vesicles (EVs), as a type of subcellular structure, have been extensively researched for their potential for developing advanced diagnostic technologies for various diseases. However, the biomolecular and biophysical heterogeneity of EVs has restricted their application in clinical settings. In this article, we developed a size-exclusion chromatography-based technique for simultaneous EV size subtyping and protein profiling. By eluting fluorescent aptamer-treated patient plasma through a size-exclusion column, the mixture can be classified into 50 nm aptamer-bound EVs, 100 nm aptamer-bound EVs and free-floating aptamers, which could further enable multiplex EV membrane protein profiling by analyzing the fluorescence intensities of EV-bound aptamers. Using this technique, we successfully identified EV size subtypes for differentiating gastrointestinal cancer prognosis states. Overall, we developed a rapid, user-friendly and low-cost EV size subtyping and protein profiling technique, which holds great potential for identifying crucial EV size subtypes for disease diagnosis in the clinic.

Dual-Ligand Synergistic Targeting Anti-Tumor Nanoplatforms with Cascade-Responsive Drug Release.

Dual-ligand targeting drug delivery nanoplatforms are considered a promising tool for enhancing the specificity of chemotherapy. However, serious off-target delivery has been observed in current dual-ligand targeting nanoplatforms, as each ligand can independently recognize receptors on the cell membrane surface and guide drug nanocarriers to different cells. To overcome this barrier, a dual-ligand synergistic targeting (DLST) nanoplatform is developed, which can guide chemotherapy treatment specifically to cancer cells simultaneously overexpressing two receptors. This nanoplatform consists of a singlet oxygen (1O2) photosensitizer-loaded nanocarrier and a drug-loaded nanocarrier with 1O2 responsiveness, which were, respectively, decorated with a pair of complementary DNA sequences and two different ligands. For cancer cells overexpressing both receptors, two nanocarriers can be internalized in larger quantities to cause DNA hybridization-induced nanocarrier aggregation, which further activates 1O2-triggered drug release under light irradiation. For cells overexpressing a single receptor, only one type of nanocarrier can be internalized in a large quantity, leading to blocked drug release due to the ultrashort action radius of 1O2. In vivo evaluation showed this DLST nanoplatform displayed highly specific tumor treatment with minimized long-term toxicity. This is a highly efficient drug delivery system for DLST chemotherapy, holding great potential for clinical applications.

Metagenomic insights into genetic factors driving bacterial niche differentiation between bulk and rhizosphere soils.

Cellular motility is crucial for effective colonization of the rhizosphere, but it is not yet clear whether bacterial motility is particularly linked to other genetic traits. Here, we applied genome-resolved metagenomics and phylogenomics to investigate the ecological significance of cellular motility for niche differentiation and the links between the genetic makeup of motile bacteria and rhizosphere colonization within a four-decade maize field experiment. Indeed, highly diverse sets of genes encoding cellular motility, including chemotaxis, flagellar assembly and motility proteins, and utilization of polymeric carbon were the important predictors of bacterial niche differentiation between bulk and rhizosphere soils. This is well exemplified by metagenome-assembled genomes encoding high motility capacity (hmc_MAGs). Their collective abundance was, on average, sixfold higher in rhizosphere soil than in bulk soil. All bulk-soil-derived MAGs showed low motility capacities (lmc). The hmc_MAGs were highly enriched in beneficial traits involved in carbohydrate utilization, assimilatory (nasA) and dissimilatory (nirBD) nitrate reduction, inorganic phosphate solubilization (gcd), and organic phosphate mineralization (phoD). Belonging to the families Sphingomonadaceae, Burkholderiaceae and Steroidobacteraceae, the hmc_MAGs showed a ninefold greater enrichment in these traits than proteobacterial lmc_MAGs and a twofold greater enrichment than 264 genomes publicly available for the above three families, thereby substantiating that a specific rhizosphere effect acted on the microbes represented by the hmc_MAGs. The particular link between the genetic capacities for high cellular motility and increased carbohydrate depolymerization as the key determinant for plant-selected rhizosphere colonization was further substantiated by the analysis of public bulk-rhizosphere soil metagenomes retrieved from wheat and cucumber field sites.

MiR-126-Loaded Immunoliposomes against Vascular Endothelial Inflammation In Vitro and Vivo Evaluation.

Due to the accompaniment of vascular endothelial inflammation during the occurrence and development of cardiovascular diseases (CVD), treatment modalities against vascular endothelial inflammation have been intensively investigated for CVD prevention and/or treatment. Vascular cell adhesion molecule-1 (VCAM-1) is a typical transmembrane inflammatory protein specifically expressed by inflammatory vascular endothelial. By inhibiting VCAM-1 expression through the miR-126 mediated pathway, vascular endothelial inflammation can be efficiently relieved. Inspired by this, we developed a miR-126-loaded immunoliposome with VCAM-1 monoclonal antibody (VCAMab) decorated at its surface. This immunoliposome can be directly targeted to VCAM-1 at the inflammatory vascular endothelial membrane surface and achieve highly efficient treatment against inflammation response. The cellular experiment results showed the immunoliposome had a higher uptake rate towards inflammatory human vein endothelial cells (HUVECs) and can significantly downregulate the VCAM-1 expression level of inflammatory HUVECs. In vivo investigation further demonstrated that this immunoliposome displayed a higher accumulation rate at vascular inflammatory dysfunction sites than its non-VCAMab-modified counterpart. These results suggest that this novel nanoplatform can effectively deliver miR-126 to vascular inflammatory endothelium, opening a new avenue for the safe and effective delivery of miRNA for potential clinical application.

Utilizing endosomal capture for tumor therapy via membrane-lytic mechanism-based Pickering emulsion.

Nanocarriers are easily captured by endosomes, where the abundant hydrolases inevitably destroy the nanocarriers and the drugs they carry, ultimately resulting in a compromised or lost therapeutic efficacy. Herein, we report a membrane-lytic mechanism-based Pickering emulsion that can in turn utilize this seemingly unfavorable endosomal capture behavior for tumor therapy. This Pickering emulsion is constructed as an oil-in-water (O/W) emulsion stabilized by the hybrid nanoparticles (HNPs) composed of two molecules with opposite charges, cetyl trimethylamine bromide (CTAB) and linoleic acid (LA), through electrostatic interaction (defined as HNPs@PE). After HNPs@PE enters the lysosomes through macropinocytosis-mediated endocytosis, LA can be protonated in response to the acidic stimulus, and causing the swelling or disintegration of HNPs due to the disrupted electrostatic interaction. The released CTAB holds strong membrane-lytic activity and can directly damage the lysosomal membranes. Under the acidic condition and the participation of excessive iron ions (II) in lysosomes, LA induces lipid peroxidation and the resulting lipid peroxides (LPO) will oxidize the lysosomal membranes, collectively causing the leakage of lysosome membranes and the release of contents into cytoplasm. Subsequently, the diffused CTAB and LPO will continue to attack the mitochondrial membranes and cell membranes, resulting in the death of different types of tumor cells both in vitro and in vivo due to membrane damage. This Pickering emulsion with membrane-lytic ability represents a potential self-anticancer nanocarrier.

Boosting ROS-Mediated Lysosomal Membrane Permeabilization for Cancer Ferroptosis Therapy.

Due to the deficient catalase, abundant reduced iron and low acidic environment in lysosomes, inducing lysosomal membrane permeabilization (LMP) through Fenton reaction-based reactive oxygen species (ROS) generation recently attracts increasing attention in cancer therapy. However, the lysosomal membranes are protected by highly glycosylated membrane proteins and several endolysosomal damage-response mechanisms can rapidly repair the injured lysosomes. To produce sufficient ROS and cause complete lysosomal membranes rupture, a lysosome-targeted ROS inducer, N-(3-Aminopropyl) morpholine grafted cross-linked lipoic acid vesicles with vitamin C-loading (VC@N3AM cLAVs), is developed. VC@N3AM cLAVs efficiently accumulate in lysosomes and convert into two redox couples LA/DHLA (dihydrolipoic acid, reduced form of LA) and VC/DHA (dehydroascorbic acid, oxidized form of VC) by the lysosomal glutathione, which can not only produce a large amount of H2 O2 by pro-oxidant action but also accelerate iron transformation through the cyclic redox reactions between each other and cause the efficient conversion of the generated H2 O2 into highly toxic •OH. Both in vitro and in vivo experiments demonstrate that VC@N3AM cLAVs can effectively enhance ROS production and boost LMP, finally initiation irreversible death of tumor cells via ferroptosis pathway, thus representing a potential anticancer drug for cancer therapy.

A hydrogel-based mechanical metamaterial for the interferometric profiling of extracellular vesicles in patient samples.

The utility of mechanical metamaterials for biomedical applications has seldom been explored. Here we show that a metamaterial that is mechanically responsive to antibody-mediated biorecognition can serve as an optical interferometric mask to molecularly profile extracellular vesicles in ascites fluid from patients with cancer. The metamaterial consists of a hydrogel responsive to temperature and redox activity functionalized with antibodies to surface biomarkers on extracellular vesicles, and is patterned into micrometric squares on a gold-coated glass substrate. Through plasmonic heating, the metamaterial is maintained in a transition state between a relaxed form and a buckled state. Binding of extracellular vesicles from the patient samples to the antibodies on the hydrogel causes it to undergo crosslinking, induced by free radicals generated via the activity of horseradish peroxidase conjugated to the antibodies. Hydrogel crosslinking causes the metamaterial to undergo fast chiral re-organization, inducing amplified changes in its mechanical deformation and diffraction patterns, which are detectable by a smartphone camera. The mechanical metamaterial may find broad utility in the sensitive optical immunodetection of biomolecules.

Application and discoveries of metabolomics and proteomics in the study of female infertility.

Introduction: Female infertility is defined as the absence of clinical pregnancy after 12 months of regular unprotected sexual intercourse. Methods: This study employed metabolomics and proteomics approaches to investigate the relationship between metabolites and proteins and female infertility. The study used metabolomics and proteomics data from the UK Biobank to identify metabolites and proteins linked to infertility. Results: The results showed that GRAM domain-containing protein 1C and metabolites fibrinogen cleavage peptides ADpSGEGDFXAEGGGVR and 3-Hydroxybutyrate had a positive correlation with infertility, whereas proteins such as Interleukin-3 receptor subunit alpha, Thrombospondin type-1 domain-containing protein 1, Intestinal-type alkaline phosphatase, and platelet and endothelial cell adhesion molecule 1 exhibited a negative correlation. These findings provide new clues and targets for infertility diagnosis and treatment. However, further research is required to validate these results and gain a deeper understanding of the specific roles of these metabolites and proteins in infertility pathogenesis. Discussion: In conclusion, metabolomics and proteomics techniques have significant application value in the study of infertility, allowing for a better understanding of the biological mechanisms underlying infertility and providing new insights and strategies for its diagnosis and treatment. These research findings provide a crucial biological mechanistic basis for early infertility screening, prevention, and treatment.

A Computational Neural Network Model for College English Grammar Correction.

For the error correction of English grammar, if there are errors in the semantic units (words and sentences), it will inevitably affect the subsequent text analysis and semantic understanding, and ultimately reduce the overall performance of the practical application system. Therefore, intelligent error detection and correction of the word and grammatical errors in English texts is one of the key and difficult points of natural language processing. This exploration innovatively combines a computational neural model with college grammar error correction to improve the accuracy of college grammar error correction. It studies the computational neural model in English grammar error correction based on a neural network named Knowledge and Neural machine translation powered College English Grammar Typo Correction (KNGTC). First, the Recurrent Neural Network is introduced, and the overall structure of the English grammatical error correction neural model is constructed. Moreover, the supervised training of Attention is discussed, and the experimental environment and experimental data are given. The results show that KNGTC has high accuracy in college English grammar correction, and the accuracy of this model in CET-4 and CET-6 writing can reach 82.69%. The English grammar error correction model based on the computational neural network has perfect function and strong error correction ability. The optimization and perfection of the model can improve students' English grammar level, which has certain practical value. After years of continuous optimization and improvement, English grammar error correction technology has entered a performance bottleneck. This mode's construction can break the current technology's limitations and bring a better user experience. Therefore, it is very valuable to study the error correction model of English grammar in practical application.

Cyclodextrin-Based Nanoplatforms for Tumor Phototherapy: An Update.

Tumor phototherapies are light-mediated tumor treatment modalities, which usually refer to tumor photothermal therapy (PTT) and photodynamic therapy (PDT). Due to the outstanding spatial-temporal control over treatment through light irradiation, tumor phototherapies display extremely low side effects during treatment and are believed to be a tumor treatment method with a clinical translation potential. However, current tumor phototherapy nanoplatforms face obstacles, including light irradiation-induced skin burning, tumor hypoxia microenvironments, limited light penetration depth, et al. Therefore, one important research direction is developing a tumor phototherapy nanoplatform with multifunctionality and enhanced pharmacological effects to overcome the complexity of tumor treatment. On the other hand, cyclodextrins (CDs) are starch-originated circular oligosaccharides with negligible toxicity and have been used to form supermolecular nanostructures through a host-guest interaction between the inner cavity of CDs and functional biomolecules. In the past few years, numerous studies have focused on CD-based multifunctional tumor phototherapy nanoplatforms with an enhanced photoeffect, responsive morphological transformation, and elevated drug bioavailability. This review focuses on the preparation methods of CD-based tumor phototherapy nanoplatforms and their unique physiochemical properties for improving anti-tumor pharmacological efficacy.

Broader environmental adaptation of rare rather than abundant bacteria in reforestation succession soil.

Revealing the responses of rare and abundant bacteria to environmental change is crucial for understanding microbial community assembly and ecosystem function. However, both the environmental adaptability and the ecological assembly processes exhibited by rare and abundant soil bacteria remain poorly understood. Here we investigated the assembly processes of rare and abundant bacteria along a chronosequence of a 35-year reforestation succession (8, 17, and 35 years), particularly with regard to their environmental adaptations. Compared to the abundant taxa, the phylogenetic clustering of rare taxa was tighter but their environmental breadth wider. Homogeneous selection (65.8%) belonging to deterministic processes dominated the rare bacterial assembly, whereas homogenizing dispersal and undominated process (57.9%) belonging to stochastic processes governed the abundant taxa. Neutral processes had a significant impact on shaping the rare taxa compared to the abundant taxa. Rare taxa were environmentally less constrained than abundant taxa. Soil EC was the major determinant factor for the assembly processes of both rare and abundant taxa. Ecological assembly processes showed a significant negative correlation with rare bacterial functional redundancies, while they had a significant positive correlation with the abundant taxa. Microbial network modularity further demonstrated that rare taxa developed stronger environmental adaptation strategies than their abundant counterparts. Our study significantly advances the knowledge of the environmental adaptability of rare and abundant bacteria and emphasizes their key role in reforestation ecological succession soils.

Genome-Resolved Metagenomics Reveals Distinct Phosphorus Acquisition Strategies between Soil Microbiomes.

Enhancing soil phosphate solubilization is a promising strategy for agricultural sustainability, while little is known about the mechanisms of how microorganisms cope with differing phosphorus availability. Using a combination of genome-resolved metagenomics and amplicon sequencing, we investigated the microbial mechanisms involved in phosphorus cycling under three agricultural treatments in a wheat-maize rotation system and two natural reforestation treatments. Available soil phosphorus was the key factor shaping bacterial and fungal community composition and function across our agricultural and reforestation sites. Membrane-bound quinoprotein glucose dehydrogenase (PQQGDH) and exopolyphosphatases (PPX) governed microbial phosphate solubilization in agroecosystems. In contrast, genes encoding glycerol-3-phosphate transporters (ugpB, ugpC, and ugpQ) displayed a significantly greater abundance in the reforestation soils. The gcd gene encoding PQQGDH was found to be the best determinant for bioavailable soil phosphorus. Metagenome-assembled genomes (MAGs) affiliated with Cyclobacteriaceae and Vicinamibacterales were obtained from agricultural soils. Their MAGs harbored not only gcd but also the pit gene encoding low-affinity phosphate transporters. MAGs obtained from reforestation soils were affiliated with Microtrichales and Burkholderiales. These contain ugp genes but no gcd, and thereby are indicative of a phosphate transporter strategy. Our study demonstrates that knowledge of distinct microbial phosphorus acquisition strategies between agricultural and reforestation soils could help in linking microbial processes with phosphorus cycling. IMPORTANCE The soil microbiome is the key player regulating phosphorus cycling processes. Identifying phosphate-solubilizing bacteria and utilizing them for release of recalcitrant phosphate that is bound to rocks or minerals have implications for improving crop nutrient acquisition and crop productivity. In this study, we combined functional metagenomics and amplicon sequencing to analyze microbial phosphorus cycling processes in natural reforestation and agricultural soils. We found that the phosphorus acquisition strategies significantly differed between these two ecosystems. A microbial phosphorus solubilization strategy dominated in the agricultural soils, while a microbial phosphate transporter strategy was observed in the reforestation soils. We further identified microbial taxa that contributed to enhanced phosphate solubilization in the agroecosystem. These microbes are predicted to be beneficial for the increase in phosphate bioavailability through agricultural practices.

Genome-resolved metagenomics identifies the particular genetic traits of phosphate-solubilizing bacteria in agricultural soil.

Bacteria play a key role in phosphate solubilization, but related genome-centric research on agricultural microbiomes is scarce. Here, we reconstructed 472 metagenome-assembled genomes (MAGs) covering agricultural soils from six long-term field trials across China. A total of 79 MAGs contained gcd encoding quinoprotein glucose dehydrogenase (GCD), which is the key biomarker for phosphate solubilization. Our findings showed that all GCD-MAGs represent potentially novel species, with gcd copy numbers varying from 1 to 10 per genome. Large genome size, a high ratio of glycosyl hydrolase genes, and increased capacity for carbohydrate utilization were specific traits of GCD-MAGs. Notably, the gcd copy number showed a significant and positive correlation with genome size. Generated using a machine learning approach, our findings were validated in a dataset of 692 genotypes covering the 18 bacterial families to which the 79 GCD-MAGs belong. Our results improve the knowledge of both the diversity and the genetic composition of phosphate-solubilizing bacteria. In particular, they reveal a genomic link between phosphate solubilization capacity and increased potential for carbohydrate metabolism, which may accelerate targeted engineering and improve management practices for sustainable agriculture.

Deciphering microbial mechanisms underlying soil organic carbon storage in a wheat-maize rotation system.

A link between microbial life history strategies and soil organic carbon storage in agroecosystems is presumed, but largely unexplored at the gene level. We aimed to elucidate whether and how differential organic material amendments (manure versus peat-vermiculite) affect, relative to sole chemical fertilizer application, the link between microbial life history strategies and soil organic carbon storage in a wheat-maize rotation field experiment. To achieve this goal, we combined bacterial 16S rRNA gene and fungal ITS amplicon sequencing, metagenomics and the assembly of genomes. Fertilizer treatments had a significantly greater effect on microbial community composition than aggregate size, with soil available phosphorus and potassium being the most important community-shaping factors. Limitation in labile carbon was linked to a K-selected oligotrophic life history strategy (Gemmatimonadetes, Acidobacteria) under sole chemical fertilizer application; defined by a significant enrichment of genes involved in resource acquisition, polymer hydrolysis, and competition. By contrast, excess of labile carbon promoted an r-selected copiotrophic life history strategy (Cytophagales, Bacillales, Mortierellomycota) under manure treatment; defined by a significant enrichment of genes involved in cellular growth. A distinct life history strategy was not observed under peat-vermiculite treatment, but rather a mix of both K-selected (Acidobacteria) and r-selected (Actinobacteria, Mortierellomycota) microorganisms. Compared to sole chemical fertilizer application, soil organic carbon storage efficiency was significantly increased by 26.5% and 50.0% under manure and peat-vermiculite treatments, respectively. Taken together, our results highlight the importance of organic material amendments, but in particular a one-time peat-vermiculite application, to promote soil organic carbon storage as a potential management strategy for sustainable agriculture.

Metagenomic insights into nitrogen and phosphorus cycling at the soil aggregate scale driven by organic material amendments.

The soil microbiome, existing as interconnected communities closely associated with soil aggregates, is the key driver in nutrient cycling. However, the underlying genomic information encoding the machinery of the soil microbiome involved in nutrient cycling at the soil aggregate scale is barely known. Here comparative metagenomics and genome binning were applied to investigate microbial functional profiles at the soil aggregate scale under different organic material amendments in a long-term field experiment. Soil samples were sieved into large macroaggregates (>2 mm), macroaggregates (0.25-2 mm) and microaggregates (<0.25 mm). Microbial taxonomic and functional alpha diversity were significantly correlated to soil NO3- and SOC. The highest abundance of nasB, nirK, and amoA genes, which are responsible for denitrification and ammonia oxidizers driving nitrification, was observed in microaggregates. Both manure and peat treatments significantly decreased the abundance of napA and nrfA that encode enzymes involved in dissimilatory nitrate reduction to ammonium (DNRA). As a biomarker for soil inorganic P solubilization, the relative abundance of gcd was significantly increased in macroaggregates and large macroaggregates. Three nearly complete genomes of Nitrososphaeraceae (AOA) and seven bacterial genomes were shown to harbor a series of genes involved in nitrification and P solubilization, respectively. Our study provides comprehensive insights into the microbial genetic potential for DNRA and P-solubilizing activity across different soil aggregate fractions and fertilization regimes.

Polymeric photothermal agents for cancer therapy: recent progress and clinical potential.

Over the past decades, near infrared light (NIR)-sensitive photothermal agents (PTAs) that can efficiently absorb light and generate heat have been investigated worldwide for cancer photothermal therapy (PTT) and the combination treatments, which have some peculiar advantages including spatiotemporal targeting, the ability-to-reverse multidrug resistance, the immunity-stimulating function, and the synergistic effect in combination treatments. In this review, we first focus on emerging melanin-like polymers and coordination polyphenol polymer-based PTAs that hold transition potential because of their facile synthesis and good biocompatibility/biodegradability. We briefly introduce polymeric PTAs for emerging NIR-II (1000-1700 nm) PTT in deep tumors to overcome shallow penetration depth and threshold irradiation intensity of NIR-I (700-900 nm). Then we discuss polymeric PTAs for combination PTT treatments with photodynamic therapy (PDT), ferroptosis therapy (ferrotherapy), and immunotherapy, which are intensively studied for achieving anticancer synergistic effects. Finally, we discuss those polymeric PTAs for reversing cancer multidrug resistance and for mild/low-temperature PTT (43 °C ≤ T < 50 °C) in contrast to conventional high-temperature PTT (>50 °C). The polymeric PTA-based PTT and the combination treatments are still being developed in the early stage and need much more effort before potential clinical transitions and applications.

Exosome-templated nanoplasmonics for multiparametric molecular profiling.

Exosomes are nanoscale vesicles distinguished by characteristic biophysical and biomolecular features; current analytical approaches, however, remain univariate. Here, we develop a dedicated platform for multiparametric exosome analysis-through simultaneous biophysical and biomolecular evaluation of the same vesicles-directly in clinical biofluids. Termed templated plasmonics for exosomes, the technology leverages in situ growth of gold nanoshells on vesicles to achieve multiselectivity. For biophysical selectivity, the nanoshell formation is templated by and tuned to distinguish exosome dimensions. For biomolecular selectivity, the nanoshell plasmonics locally quenches fluorescent probes only if they are target-bound on the same vesicle. The technology thus achieves multiplexed analysis of diverse exosomal biomarkers (e.g., proteins and microRNAs) but remains unresponsive to nonvesicle biomarkers. When implemented on a microfluidic, smartphone-based sensor, the platform is rapid, sensitive, and wash-free. It not only distinguished biomarker organizational states in native clinical samples but also showed that the exosomal subpopulation could more accurately differentiate patient prognosis.

Therapeutic strategy of central vein perforation accompanied by a mediastinal lesion after catheterization.

Central vein perforation associated with a mediastinal lesion is a rare complication of catheterization. A 50-year-old woman was diagnosed with chronic kidney disease and required hemodialysis treatment. The patient developed central vein injury during attempted placement of a double-channel catheter. A computed tomographic scan and venography showed that the catheter had punctured the mediastinum from the central vein. After comprehensive assessment and multidisciplinary consultation, percutaneous catheter thrombin injection with follow-up balloon dilatation under fluoroscopy guidance successfully fixed the perforation. We summarize the therapeutic strategy of this complication and other treatment options, and discuss the related literature of central vein injury.