Repurposing indocyanine green: exploring the potential of an old drug in modern medicine.

The repurposing of existing drugs, referred to as theranostics, has made profound impacts on precision medicine. Indocyanine green (ICG), a well-established and clinical dye, has continued to be a star agent, described as a multifunctional molecule with concurrent photo- or sono-sensitiveness capabilities and co-delivery accessibility, showing remarkable potential in the area of unimodal or multimodal imaging-guided therapy of various diseases, leading to the extensive consideration of immediate clinical translations. In this review, we strive to bring the understanding of repurposing performance assessment for ICG into practice by clarifying the relationships between its features and applicability. Specifically, we address the obstacles encountered in the process of developing an ICG repurposing strategy, as well as the noteworthy advancements made in the field of ICG repurposing. We also go into detail about the structure-function correlations of drugs containing ICG and how different structural groups significantly affect the physicochemical properties.

Therapeutic Drug Monitoring of Linezolid in Drug-Resistant Tuberculosis Patients: Clinical Factors and Hematological Toxicities.

Purpose: Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (Cmax), but the factors affecting linezolid Cmax and evidences on therapeutic drug monitoring to anticipate toxicity in drug-resistant tuberculosis (DR-TB) patients have not been clarified clearly. This study aimed to explore the factors influencing linezolid Cmax and investigate the association between linezolid concentration and hematological toxicity. Patients and Methods: This study included patients with drug-resistant tuberculosis treated with linezolid from January 2022 to September 2023. We analyzed the factors affecting linezolid Cmax using chi-squared and binary logistic regression. The diagnostic utility of linezolid Cmax in predicting hematological toxicity was evaluated using receiver operating characteristic (ROC) analysis. Results: A total of 76 patients were enrolled in the study. 63.20% met the standard rates for linezolid Cmax. Age (P=0.036), weight (P=0.0016), and creatinine clearance (P=0.0223) significantly correlated with the Cmax. Hematological toxicity was observed in 46.05% (35/76) of patients, characterized by thrombocytopenia (31.58%, 24/76), anemia (6.58%, 5/76), and leukopenia (21.05%, 16/76). ROC curve analysis confirmed the predictive value of linezolid Cmax for thrombocytopenia with an area under curve of 0.728. Conclusion: Suboptimal linezolid Cmax was prevalent among patients with DR-TB, with age, weight, and renal function emerging as influential factors. Elevated linezolid Cmax increases the risk of thrombocytopenia. Meticulous monitoring of linezolid Cmax is imperative during anti-DR-TB therapy to tailor treatment and mitigate hematological toxicity.

Oyster shell for drinking water filtration compared with granular activated carbon: advantages and limitations.

Deliberate media selection can be conducted to achieve targeted objective in filters. In this study, three biofilters (BFs) packed with calcinated oyster shell (COS), granular activated carbon (GAC), and COS + GAC (Mix) were set up in parallel following a rough filter packed with natural oyster shell to compare the performance for treating micro-polluted source water. Different media showed selective removal effects for different pollutants. GAC outperformed COS in terms of TOC and UV254. COS achieved higher reduction in turbidity than GAC. Due to the removal of total bacteria, the absolute and relative abundance of antibiotic resistance genes (ARGs) both decreased much in rough filter treated water (1.16 × 1014 to 1.40 × 1013 copies L-1 and 81.6 to 36.9%, respectively). The highest diverse and rich bacterial community was found in the biofilms on the COS filler, so microbial leakage gave rise to high bacterial content, leading to the highest absolute abundance of ARGs in COS BF effluent (2.11 × 1013 copies L-1). The highest relative abundance of ARGs (41.2%) was found in GAC BF effluent. SourceTracker and biomarker analysis both suggested that treatment process played a more important role in shaping the bacterial community structure in Mix BF effluent than single media BFs, which contributed to the lowest absolute (8.69 × 1012 copies L-1) and relative abundance (25.2%) of ARGs in Mix BF effluent among the three BFs. Our results suggested that mix COS + GAC can not only give full play to their respective advantages for traditional pollutants, but also achieve highest reduction in ARGs.

Occurrence, distribution, and characteristics of microplastics in agricultural soil around a solid waste treatment center in southeast China.

Purpose: In recent years, microplastic (MP) contamination has raised enormous concern. However, data on the influence of solid waste treatment systems on MP pollution around agricultural soil are lacking. This study investigated the distribution and characteristics of MPs in agricultural soil surrounding a solid waste treatment center in southeastern China. Materials and methods: Fifty-seven agricultural topsoil samples around the solid waste treatment center were collected. The samples were pretreated by drying, flotation separation using NaCl solution, and digestion by H2O2. The abundance and morphological characteristics of MPs were determined by a microscope, followed by Raman spectroscopy analysis identified polymer types and SEM-EDS analysis observed surface morphology and the type of metals accumulated on the MPs. Results and discussion: Soil MPs' abundance ranged from 280 to 2360 items/kg, while a higher abundance of MPs was distributed in the downwind area. The < 1-mm MPs were dominant, and white fragment MPs were widely found. Polyethylene (52.86%) and polypropylene (27.14%) were the most common. Moreover, SEM-EDS images illustrated that MPs were significantly weathered and showed the uneven distribution of metal(loid) elements on the surface, implying that MPs may migrate as heavy metal vectors to threaten agroecosystem safety. Conclusions: This study reveals the distribution and characteristics of MPs in agricultural soil surrounding a solid waste treatment center in southeastern China, as well as the potential source of soil MPs, and provides systematic data for further research on MP pollution in agricultural soil. Supplementary Information: The online version contains supplementary material available at 10.1007/s11368-022-03341-6.

Efficiency Assessment of Hazardous Waste Disposal in EU Countries: A Three-Stage Super-Efficiency Data Envelopment Analysis Model.

Hazardous waste pollutes the air, soil, and water and adversely affects human health if not disposed of safely. Analysis of the efficiency of hazardous waste disposal is essential to sustainable development. This paper uses the three-stage super-efficiency Data Envelopment Analysis model to measure the efficiency of 28 EU countries from 2004 to 2016. To ensure the reliability of the results, the article utilizes a one-way ANOVA statistical test to verify whether DEA results vary significantly across various EU countries. This article discusses "how inputs and outputs can be adjusted to eliminate inefficiencies" to suggest a targeted improvement. The third stage supper efficiency DEA results shows that the efficiency varies significantly across different EU countries. The main reasons for the low efficiency are high generated hazardous waste, management expenditure, greenhouse gas emissions, and inadequate waste disposal volume. Targeted proposals from three aspects are given for policymakers in EU countries: Build a resource recycling system to reduce hazardous waste. Establish a sound fee management system to reduce expenses. Optimization of disposal technology to improve incineration efficiency.

Metal Ion-Based Supramolecular Self-Assembly for Cancer Theranostics.

Metal-ion-based self-assembly supramolecular theranostics exhibit excellent performance in biomedical applications owing to their potential superiorities for simultaneous precise diagnosis, targeted drug delivery, and monitoring the response to therapy in real-time. Specially, the rational designed systems could achieve specific in vivo self-assembly through complexation or ionic interaction to improve tissue-specific accumulation, penetration, and cell internalization, thereby reducing toxicities of drugs in diagnostics and therapy. Furthermore, such imaging traceable nanosystems could provide real-timely information of drug accumulation and therapeutic effects in a non-invasive and safe manner. Herein, the article highlights the recent prominent applications based on the metal ions self-assembly in cancer treatment. This strategy may open up new research directions to develop novel drug delivery systems for cancer theranostics.

Superior Fluorescent Nanoemulsion Illuminates Hepatocellular Carcinoma for Surgical Navigation.

Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, poses a severe threat to public health. Intraoperative fluorescence imaging provides a golden opportunity for surgeons to visualize tumor-involved margins, thereby implementing precise HCC resection with minimal damage to normal tissues. Here, a novel-acting contrast agent, which facilely bridges indocyanine green (ICG) and lipiodol using self-emulsifying nanotechnology, was developed for optical surgical navigation. Compared to clinically available ICG probe, our prepared nanoemulsion showed obviously red-shifted optical absorption and enhanced fluorescence intensity. Further benefiting from the shielding effect of lipiodol, the fluorescence stability and anti-photobleaching ability of nanoemulsion were highly improved, indicating a great capacity for long-lasting in vivo intraoperative imaging. Under the fluorescence guidance of nanoemulsion, the tumor tissues were clearly delineated with a signal-to-noise ratio above 5-fold, and then underwent a complete surgical resection from orthotopic HCC-bearing mice. Such superior fluorescence performances, ultrahigh tumor-to-liver contrast, as well as great bio-safety, warrants the great translational potential of nanoemulsion in precise HCC imaging and intraoperative navigation.

Reutilization of waste oyster shell as filler for filter for drinking water pretreatment: Feasibility and implication.

Oyster shell (OS) is a kind of reusable resource that can serve as carbon source, biofilms carrier and basifying agent, suggesting it is an attractive filler option for biofiltration, but studies on its application in drinking water treatment are limited. In this study, one pilot-scale up-flow filter filled with OS media were designed to pretreat surface source water. Filter performance and biological functions were investigated to determine its application scope. The results showed that effluent pH increased and was stable around 7.5 due to the alkalinity provided by OS and its buffering capacity. High and stable removal efficiencies of turbidity (mostly >60%) were achieved. The removal efficiencies of NH4+-N changed in a wide range (mostly <30%). TOC and UV254 removal rate was low (<10%). The biofilms formation period took about 45 days. During this period, this filter mainly removed pollutants through adsorption by OS. High-throughput sequencing results showed that functional taxa did not play a key role after adsorption saturation in early operation period. Functional microbial taxa formed on the OS surface after long-term operation and NH4+-N removal rate increased to some extent. Our results suggested that unburned OS filter can be used as rough filter for turbidity removal instead of coagulation and sedimentation process. Preoxidation, calcination of OS, mixed with other filler and are recommended to improve the performance if it would be used for biofiltration. This study provides an insight for the reuse of OS in drinking water treatment.

Impact of different source-water switching patterns on the stability of drinking water in an estuarine urban water distribution system.

Source-water switching can lead to instability in drinking water distribution systems. In estuarine cities using surface water as source water where salt tide occasionally happens, the influence can be particularly complex due to changes of Larson Index (LI). The objective of this study was to investigate the effects of different switching patterns on the stability of water in an estuarine city. Fluctuated LI was found in the current distribution system. LI of the new source water was lower and more stable. Susceptible areas with a high frequency of over standard water quality were identified and pipe scales there were mainly composed of relatively stable iron oxides with dense crystal structures (Fe3O4 and α-FeOOH). Two old pipe sections were used to simulate different switching patterns. The microbial risk did not increase significantly when the original and new water sources were combined in different ratios (2∶8, 5∶5), when multiple water sources were used (3∶3∶4) or when salinity increased. The better water quality, lower LI of the new source water, and stability of the current distribution system together contributed to the biostability. Total iron increased after switching, then declined and stabilized for most switching patterns. Salt tide can lead to sharp iron release. The results provided insightful information for distribution systems that have cast iron pipes and that might encounter source-water switching patterns.

Smart NIR-II croconaine dye-peptide for enhanced photo-sonotheranostics of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is associated with high morbidity and mortality rates. The development of novel nanomaterials represents an important direction for precise HCC theranostics. The combination of photothermal and sonodynamic therapy has provided great benefits for HCC therapy. Theranostic agents in the second near-infrared window (NIR-II, 1000-1700 nm) show great prospects because of their extraordinarily high detection sensitivity, resolution, and deep penetration. Methods: A sharp pH-sensitive self-assembling Glypican-3 (GPC3)-binding peptide (GBP) dye, CR-PEG-GBP, was developed as an intelligent nanoprobe for NIR-II imaging and photoacoustic (PA) imaging-guided photothermal therapy (PTT) and sonodynamic therapy (SDT) of HCC. Results: This small molecule assembled nanoprobe exhibited advantageous properties, such as responding to a decrease in pH (from normal tissue (pH 7.4) to the tumor microenvironment (pH ~6.5)) and aggregating - from small nanoprobes (<20 nm at pH 7.4) - into large nanoparticles (>160 nm at pH 6.5 and >510 nm at pH 5.5) that enables enhanced imaging and therapeutic effects. Because CR-PEG-GBP can self-aggregate in situ in an acidic tumor microenvironment, it shows high tumor accumulation and long tumor retention time, while being excretable from normal tissues and safe. Conclusions: This intelligent self-assembling small molecule strategy provides a simple yet efficient solution for HCC theranostics and may open up new avenues for designing clinically translatable probes for HCC treatment.

[Occurrence Characteristics of Microplastics in Mangrove Sediments in the Jiulong River Estuary and the Association with Heavy Metals].

The abundance and morphological characteristics of microplastics in the surface sediments of mangrove wetlands in the Jiulong River estuary were analyzed. The main sources of microplastics were also explored in detail. The results showed that the abundance of microplastics ranged from 640 to 1140 n·kg-1 (dry sediment), with an average of 935 n·kg-1, exhibiting a medium level compared with other domestic and abroad mangrove areas. The microscopic observation found that the microplastics were granular (39%), fragmented (31%), and fibrous (30%); the color was mainly transparent (55%); and the particle size was less than 1 mm (92%). As observed via Raman spectroscopy, the main polymer types of the microplastics were identified to be polyethylene, polyethylene terephthalate, and polypropylene, accounting for 57%, 34%, and 9%, respectively. The main sources of microplastics were the plastic waste from aquaculture nearby, urban and rural domestic or industrial wastewater in the basin, and the plastic waste transported here by the tide. Additionally, SEM-EDS results showed that the surface of the microplastics had the characteristics of depression, porosity, and tearing, and some heavy metal elements such as Pb, Cd, Hg, Cr, Fe, Mn, Zn, and Cu were attached to the microplastics. Microplastics may be transferred to the sediments as carriers of heavy metals, posing a potential threat to wetland ecological security.

Solidification of chromium-containing sludge with attapulgite combined alkali slag.

To solve the harm caused by hazardous chromium-containing sludge (CCS, chromium-containing sludge) waste to humans and the environment, this study used attapulgite to strengthen alkali slag to prepare cementitious materials to solidify/stabilize CCS. Single-factor and orthogonal experiments were used to optimize the preparation parameters of alkali slag cementitious materials. The compressive strength, heavy metal leaching toxicity, and microscopic characterization of a CCS solidified body were tested to investigate the solidification effect and mechanism of CCS formation. The best attapulgite content was 4%; the solidified body after the treatment of chromium-containing sludge had a good performance of heavy metal leaching and mechanical properties. The addition of attapulgite enhanced the compressive strength. Compared with the original CCS, the leaching concentration of heavy metals in the solidified body was significantly reduced. Among them, the solidified efficiency of chromium is stable above 90%. The changes in the results of XRD and FTIR for each component were studied. It indicated that the solidified body may solidify/stabilize heavy metals through physical encapsulation of the amorphous form and chemical immobilization. This research recognized the use of waste to treat waste, realized the combined effect of solidification/adsorption, and indicated the possibility of application of attapulgite and its solidified products in construction.

A pure nanoICG-based homogeneous lipiodol formulation: toward precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization.

PURPOSE: To surmount the critical issues of indocyanine green (ICG), and thus achieving a precise surgical navigation of primary liver cancer after long-term transcatheter arterial embolization. METHODS: In this study, a facile and green pure-nanomedicine formulation technology is developed to construct carrier-free indocyanine green nanoparticles (nanoICG), and which subsequently dispersed into lipiodol via a super-stable homogeneous lipiodol formulation technology (SHIFT nanoICG) for transcatheter arterial embolization combined near-infrared fluorescence-guided precise hepatectomy. RESULTS: SHIFT nanoICG integrates excellent anti-photobleaching capacity, great optical imaging property, and specific tumoral deposition to recognize tumor regions, featuring entire-process enduring fluorescent-guided precise hepatectomy, especially in resection of the indiscoverable satellite lesions (0.6 mm × 0.4 mm) in rabbit bearing VX2 orthotopic hepatocellular carcinoma models. CONCLUSION: Such a simple and effective strategy provides a promising avenue to address the clinical issue of clinical hepatectomy and has excellent potential for a translational pipeline.

Repurposing ICG enables MR/PA imaging signal amplification and iron depletion for iron-overload disorders.

Precise and noninvasive theranostic methods to quantify and deplete focal iron are of crucial importance for iron-overload disorders. Here, we developed an indocyanine green (ICG)­based imaging platform to reveal Fe3+ in vitro and in vivo. The high sensitivity and specificity of ICG-Fe interaction facilitated MR images with a marked correlation between T1 signal intensity ratio (T1SIR) changes and Fe3+ concentration in rodent models and humans. On the basis of these findings, a rational design for coordination-driven self-assembly ICG-Lecithin (ICG/Leci) was proposed to determine Fe3+. The enhancement of photoacoustic signal at 890 nm with increasing Fe3+ concentration showed an over 600% higher linear slope than that of T1SIR changes in animal models. ICG/Leci also promoted a 100% increase in iron depletion in the liver compared with deferoxamine. The high MR sensitivity and superior photoacoustic contrast, combined with enhanced iron depletion, demonstrate that ICG/Leci is a promising theranostic agent for simultaneous detection and treatment of iron-overload disorders.

Preparation of Glass-Ceramics via Cosintering and Solidification of Hazardous Waste Incineration Residue and Chromium-Containing Sludge.

Residues from the incineration of hazardous wastes are classified as hazardous byproducts because they contain heavy metals. Chromium-containing sludge (CCS) is industrial sludge produced during the electroplating process and includes heavy metals, such as Cr, Pb, and Cu. These heavy metals can infiltrate natural ecosystems and cause significant environmental damage. To limit the toxicity of leached products, hazardous waste incineration residues (HWIRs) can be repurposed as raw materials for producing glass-ceramics. In this study, we designed an orthogonal experiment to optimize the heat treatment process, yielding glass-ceramics with excellent properties and realizing heavy metal solidification. The toxic characteristic leaching procedure was used to determine the leaching toxicity of the cosintered solidified heavy metals, revealing that their solidification efficiencies exceed 90%. Moreover, X-ray diffraction analysis indicates that certain heavy metals participate in the formation of heavy-metal-containing crystal lattices (FeCr2O4 and PbFe12O19), thereby reducing their leaching concentration. These results show that cosintering HWIR and CCS is an effective approach for heavy metal solidification and provides valuable insights into its utilization for producing building materials.

Variable metal resistance of P. putida CZ1 biofilms in different environments suggests its remediation application scope.

Pseudomonas putida is potentially used in the bioremediation of heavy metals (HMs). Its response to different HMs in different environments is still not fully understood. This study investigated resistance against 12 kinds of metals by P. putida CZ1 planktonic cells and its biofilm in LB and mineral medium (MM). P. putida CZ1 biofilms have high resistance and accumulation capacity for Cu2+, Zn2+, Pb2+, Fe3+, Mn2+, Al3+ and Ni2+, but less resistance to Co2+, Cd2+, Cr2O72-, Ag+ and Hg2+. Biofilms were 2-8 times more resistant to Cu2+ and Zn2+ than planktonic cells. There was a strong correlation between the P content and the accumulation of Cu2+, Zn2+, Fe3+, Mn2+, Pb2+, Ni2+and Al3+ respectively. Confocal laser scanning microscopy (CLSM) combined with live/dead staining study found that cells in the biofilms can keep viable after 36 h under MIC of Cu2+ or Zn2+ both in LB and MM. When the metal concentration increased, cells can be killed gradually. For Cu2+, Zn2+, Fe3+, Mn2+, Pb2+ and Ni2+, higher resistance was found in MM (2-4 times higher) than in LB and higher accumulation of these metals were also found in MM. P. putida CZ1 biofilm cultured in MM with citric acid as carbon source had stronger resistance and accumulation ability to Cu2+, Zn2+, Pb2+, Fe3+, Mn2+, and Ni2+. This suggested that P. putida CZ1 had greater remediation potential for these metals in organic acid rich environments.

The role of circRNA derived from RUNX2 in the serum of osteoarthritis and its clinical value.

BACKGROUND: Circular RNA (circRNA) has been shown to affect the pathological process of osteoarthritis (OA) and is expected to become a potential marker for disease diagnosis. This study aimed to investigate the association between circRNA derived from the gene of runt-related transcription factor 2 (RUNX2) and OA risk. METHODS: The expression profile of RUNX2-derived circRNAs in serum of OA patients was detected. Then, the cytological localization of screened differential circRNAs was studied. Luciferase (LUC) reporter assay was used to identify the microRNA (miRNA) sponge capacity of the circRNAs. Bioinformatics analysis was used to construct the functional pathway of this circRNA-miRNAs network. And then, the diagnostic value of RUNX2-derived circRNAs in OA was evaluated. RESULTS: RUNX2-derived hsa_circ_0005526 (circ_RUNX2) is significantly highly expressed in OA serum and mainly located in the cytoplasm within the cartilage cell by sponging multiple miRNAs (miR-498, miR-924, miR-361-3p, and miR-665). Bioinformatics analysis showed ECM-receptor interaction pathway ranked the most significant pathway of circ_RUNX2-miRNAs regulatory network in KEGG database. The ROC curve showed that there may be good diagnostic value of serum circ_RUNX2 in OA. CONCLUSION: RUNX2-derived circ_RUNX2 may be involved in OA development via ECM-receptor interaction pathways and may be used as potential clinical indicator of OA.

Efficient electrokinetic remediation of heavy metals from MSWI fly ash using approaching anode integrated with permeable reactive barrier.

During electrokinetic remediation (EKR) of heavy metals (HMs) (Pb, Zn, Cu, and Cd) from municipal solid waste incineration (MSWI) fly ash enhanced by a permeable reactive barrier (PRB), the nearer to the anode, the higher the concentration of H+ ions and the greater the remediation effect. Therefore, a potentially new method of PRB-enhanced EKR using an approaching anode (A-EKR + PRB) was studied to help H+ ions to quickly migrate to the sample near the cathode. Consequently, the HM leaching and total concentrations were reduced, while an energy reduction of nearly 40% was achieved. The results showed that the best remediation ability was obtained when MSWI fly ash was treated for 16 days at a voltage gradient of 2.5 V/cm, the approaching anode was moved after 4 days, and the PRB contained 10 g of activated carbon. After remediation, the environmental risk analysis showed that A-EKR + PRB reduced all the fractions of HMs, especially the acid extractable and oxidizable fractions, which might have been due to the enhancement of acid dissolution and oxidation by the approaching anode. In addition, the environmental risks of the remaining HMs were reduced, and the results indicated that A-EKR + PRB is an advisable choice for remediation of MSWI fly ash.

Ultrasound activated nanosensitizers for sonodynamic therapy and theranostics.

Sonodynamic therapy (SDT) is a promising non-invasive therapeutic modality with an extensive application prospect. Due to the engineerable nature of nanotechnology, nanosensitizers with predominant advantages of increased SDT efficacy and targeting specificity have attracted more and more research recently. In this review, we introduce the current investigations of nanosonosensitizers and focus on the potential strategies on nanoparticles-assisted sonosensitizers to enhance SDT efficacy. We extensively discuss the biomedical applications of ultrasound activated nanosonosensitizers in SDT and theranostics.