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.

Enhanced Mechanical Strength and Sustained Drug Release in Carrier-Free Silver-Coordinated Anthraquinone Natural Antibacterial Anti-Inflammatory Hydrogel for Infectious Wound Healing.

The persistent challenge of healing infectious wounds and the rise of bacterial resistance represent significant hurdles in contemporary medicine. In this study, based on the natural small molecule drug Rhein self-assembly to form hydrogels and coordinate assembly with silver ions (Ag+), a sustained-release carrier-free hydrogel with compact structure is constructed to promote the repair of bacterial-infected wounds. As a broad-spectrum antimicrobial agent, Ag+ can avoid the problem of bacterial resistance caused by the abuse of traditional antibiotics. In addition, due to the slow-release properties of Rhein hydrogel, continuous effective concentration of Ag+ at the wound site can be ensured. The assembly of Ag+ and Rhein makes the hydrogel system with enhanced mechanical stability. More importantly, it is found that Rhein effectively promotes skin tissue regeneration and wound healing by reprogramming M1 macrophages into M2 macrophages. Further mechanism studies show that Rhein realizes its powerful anti-inflammatory activity through NRF2/HO-1 activation and NF-κB inhibition. Thus, the hydrogel system combines the excellent antibacterial properties of Ag+ with the excellent anti-inflammatory and tissue regeneration ability of Rhein, providing a new strategy for wound management with dual roles.

Nurses Caring for Older Adult Family Members: Disclosing Caregiving to Work Supervisors.

BACKGROUND: Disclosure of family caregiving to work supervisors is needed for nurses to access work support for family caregiving. Little is known about characteristics of nurses who decide to/not to disclose family caregiving to supervisors. OBJECTIVE: The objective was to examine characteristics of nurses based on whether they disclosed caregiving responsibilities to their nursing supervisors and describe reasons for non-disclosure. METHODS: This was a secondary analysis of a cross-sectional survey. Registered nurses who had a work supervisor and cared for an older adult family member completed a survey including demographics, work and caregiving characteristics, and disclosure. Descriptive statistics and binary logistic regression were conducted. RESULTS: The sample included 162 nurses. Participants were on average 50 years old, 90.1% female, 65.4% married, and 80.9% were caring for a parent or parent-in-law. The disclosure was more likely among nurses who provided higher intensity care (hours of care), cared for a parent or in-law, or had a quality caregiver-care recipient relationship. Reasons for non-disclosure included wanting to separate personal and work life, discomfort, and fear of consequences. CONCLUSIONS: Nurses struggle with similar disclosure challenges as other family caregivers. Care intensity, caregiver-care recipient relationships, and care stress were associated with disclosure behaviors.

Analysis of the impact of the combined use of rebar bolts and FRP bolts in the roadway enclosure.

In order to investigate the support effect of the combination of FRP bolts and rebar bolts in the roadway, taking a coal mine as the background of the project, research and analysis of the engineering geological conditions of the mine and the layout of the mining roadway, stress analysis of the roadway peripheral rock, and put forward the combination of rebar and FRP bolts in the roadway peripheral rock support program. Based on different scenarios, FLAC3D was applied to simulate and analyze the distribution of axial force, maximum principal stress of the surrounding rock, yield damage of the surrounding rock, and displacement of the surrounding rock under three conditions: no support, full rebar bolt support, and combined rebar and FRP bolt support. The results show that (1) In the pre-action period between the bolt and the surrounding rock of the roadway, the FRP bolt carries the force first; in the late action period, the rebar bolt and the FRP bolt carry the force together. (2) From the analysis of the stress concentration degree of the maximum principal stress of the roadway surrounding rock, the horizontal displacement of the roadway surrounding rock and the distribution characteristics of the plastic zone of the roadway surrounding rock, it can be concluded that the support strength of FRP bolts is slightly lower than that of rebar bolts. (3) Under the state of combined support of FRP and rebar bolts, the range of plastic zone of surrounding rock in the roadway is analyzed in comparison with the effect of full rebar bolt support, and the range of reduction of plastic zone of surrounding rock is not obvious, and the effect of full rebar bolt support and combined support of FRP and rebar bolts on controlling the damage of surrounding rock is similar. (4) The side part of the roadway perimeter rock mining adopts FRP bolts instead of rebar bolts, and if the FRP bolts are not damaged, the combination of FRP and rebar bolts can be used for support, which can maintain the stability of the roadway perimeter rock.

The vertically-stratified resistomes in mangrove sediments was driven by the bacterial diversity.

Early evidence has elucidated that the spread of antibiotic (ARGs) and metal resistance genes (MRGs) are mainly attributed to the selection pressure in human-influenced environments. However, whether and how biotic and abiotic factors mediate the distribution of ARGs and MRGs in mangrove sediments under natural sedimentation is largely unclear. Here, we profiled the abundance and diversity of ARGs and MRGs and their relationships with sedimental microbiomes in 0-100 cm mangrove sediments. Our results identified multidrug-resistance and multimetal-resistance as the most abundant ARG and MRG classes, and their abundances generally decreased with the sediment depth. Instead of abiotic factors such as nutrients and antibiotics, the bacterial diversity was significantly negatively correlated with the abundance and diversity of resistomes. Also, the majority of resistance classes (e.g., multidrug and arsenic) were carried by more diverse bacterial hosts in deep layers with low abundances of resistance genes. Together, our results indicated that bacterial diversity was the most important biotic factor driving the vertical profile of ARGs and MRGs in the mangrove sediment. Given that there is a foreseeable increasing human impact on natural environments, this study emphasizes the important role of biodiversity in driving the abundance and diversity of ARGs and MRGs.

Vertically stratified methane, nitrogen and sulphur cycling and coupling mechanisms in mangrove sediment microbiomes.

BACKGROUND: Mangrove ecosystems are considered as hot spots of biogeochemical cycling, yet the diversity, function and coupling mechanism of microbially driven biogeochemical cycling along the sediment depth of mangrove wetlands remain elusive. Here we investigated the vertical profile of methane (CH4), nitrogen (N) and sulphur (S) cycling genes/pathways and their potential coupling mechanisms using metagenome sequencing approaches. RESULTS: Our results showed that the metabolic pathways involved in CH4, N and S cycling were mainly shaped by pH and acid volatile sulphide (AVS) along a sediment depth, and AVS was a critical electron donor impacting mangrove sediment S oxidation and denitrification. Gene families involved in S oxidation and denitrification significantly (P < 0.05) decreased along the sediment depth and could be coupled by S-driven denitrifiers, such as Burkholderiaceae and Sulfurifustis in the surface sediment (0-15 cm). Interestingly, all S-driven denitrifier metagenome-assembled genomes (MAGs) appeared to be incomplete denitrifiers with nitrate/nitrite/nitric oxide reductases (Nar/Nir/Nor) but without nitrous oxide reductase (Nos), suggesting such sulphide-utilizing groups might be an important contributor to N2O production in the surface mangrove sediment. Gene families involved in methanogenesis and S reduction significantly (P < 0.05) increased along the sediment depth. Based on both network and MAG analyses, sulphate-reducing bacteria (SRB) might develop syntrophic relationships with anaerobic CH4 oxidizers (ANMEs) by direct electron transfer or zero-valent sulphur, which would pull forward the co-existence of methanogens and SRB in the middle and deep layer sediments. CONCLUSIONS: In addition to offering a perspective on the vertical distribution of microbially driven CH4, N and S cycling genes/pathways, this study emphasizes the important role of S-driven denitrifiers on N2O emissions and various possible coupling mechanisms of ANMEs and SRB along the mangrove sediment depth. The exploration of potential coupling mechanisms provides novel insights into future synthetic microbial community construction and analysis. This study also has important implications for predicting ecosystem functions within the context of environmental and global change. Video Abstract.

Identification microenvironment immune features and key genes in elderly stroke patients.

BACKGROUND: The purpose of this study was to identify the signaling pathways and immune microenvironments related to elderly stroke patients. METHODS: We downloaded the public transcriptome data (GSE37587) from the gene expression omnibus and divided the patients into young and old groups and identified differentially expressed genes (DEGs). Gene ontology function analysis, Kyoto encyclopedia of genes and genomes pathway analysis, and gene set enrichment analysis (GSEA) were performed. A protein-protein interaction network was constructed and hub genes were identified. Gene-miRNA, gene-TF, and gene-drug networks were constructed using the network analyst database. The immune infiltration score was evaluated using single-sample gene set enrichment analysis GSEA, its correlation with age was computed and visualized using R software. RESULTS: We identified 240 DEGs, including 222 upregulated and 18 downregulated DEGs. Gene ontology enrichment was significantly enriched in response to the virus, type I interferon signaling pathway, cytological component, focal adhesion, cell-substrate adherents junction, and the cytosolic ribosome. GSEA identified the following mechanisms: heme metabolism, interferon gamma response, and interferon alpha response. Ten hub genes included interferon alpha-inducible protein 27, human leucocyte antigen-G, interferon-induced protein with tetratricopeptide repeats 2, 2'-5'-oligoadenylate synthetase 2, interferon alpha-inducible protein 6, interferon alpha-inducible protein 44-like, interferon-induced protein with tetratricopeptide repeats 3, interferon regulatory factor 5, myxovirus resistant 1, and interferon-induced protein with tetratricopeptide repeats 1. Quantitative analysis of immune infiltration showed that increased age was significantly positively correlated with myeloid-derived suppressor cells and natural killer T cells, and negatively correlated with immature dendritic cells. CONCLUSION: The present research could help us better understand the molecular mechanisms and immune microenvironment of elderly patients with stroke.

Food web dynamics in the mangrove ecosystem of the Pearl River Estuary surrounded by megacities.

Global recognition that mangroves support coastal ecosystem services has increased; however, studies on trophic dynamics in mangrove ecosystems remain limited. We seasonally analysed the δ13C and δ15N of 34 consumers and 5 diets to elucidate the food web dynamics in the Pearl River Estuary (PRE). Fish had a large niche space during the monsoon summer, reflecting increased trophic roles. In contrast, the small niche space of benthos over seasons reflected consistent trophic positions. Consumers mainly utilized plant-derived organic matters in the dry season and particulate organic matters in the wet season. The present study with literature reviews revealed characteristics of the PRE food web with the depleted δ13C and enriched δ15N, indicating a high contribution of mangrove-derived organic carbon and sewage input, particularly in the wet season. Overall, this study confirmed the seasonal and spatial trophic dynamics in mangrove forests surrounding megacities for future sustainable mangrove ecosystem management.

An exploratory human study of superstable homogeneous lipiodol-indocyanine green formulation for precise surgical navigation in liver cancer.

The clinical applications of transcatheter arterial embolization (TAE) conversion therapy combined with hepatectomy have been severely restricted by ill-defined tumoral boundaries and miniscule hidden lesions. Fluorescent surgical navigation is a promising method for overcoming these barriers. However, sufficient delivery of the fluorescent probe into the tumor region after long-term TAE is challenging due to blockade of the tumor-supplying artery. Here, a super-stable homogeneous intermix formulating technology (SHIFT) to physically mix lipiodol and indocyanine green (ICG) formulation (SHIFT and ICG) for fluorescent surgical navigation after long-term TAE conversion therapy is provided. Through the retrospective study of 45 clinical liver cancer patients, it is found that SHIFT and ICG formulation have excellent tumor deposition effect and safety. During surgical resection after long-term TAE conversion therapy, SHIFT and ICG could clearly identify in real time the full tumor regions and boundaries and had a high signal-to-normal tissues ratio-even the indistinguishable satellite lesions could be identified with a strong fluorescence intensity. Meanwhile, SHIFT and ICG could improve operative, anesthetic, and postoperative variables associated with postoperative complications. This simple and effective SHIFT could provide precise fluorescent navigation for surgical resection following long-term embolization therapy in clinical practice and has great potential for a translational pipeline.

Superstable homogeneous lipiodol-ICG formulation: initial feasibility and first-in-human clinical application for ruptured hepatocellular carcinoma.

The most common treatment of spontaneous tumor rupture hemorrhage (STRH) is transcatheter arterial embolization (TAE) followed by liver resection, and surgical navigation using near-infrared fluorescence is effective method for detecting hidden lesions and ill-defined tumor boundaries. However, due to the blockage of the tumor-supplying artery after effective TAE treatment, it is difficult to deliver sufficient fluorescent probes to the tumor region. In this study, we report on the successful application of superstable homogeneous intermixed formulation technology (SHIFT) in precise conversion hepatectomy for ruptured hepatocellular carcinoma (HCC). A homogeneous lipiodol-ICG formulation obtained by SHIFT (SHIFT-ICG) was developed for clinical practice for STRH. A ruptured HCC patient received the combined protocol for embolization and fluorescence surgical navigation and exhibited excellent hemostatic effect. Lipiodol and ICG were both effectively deposited in the primary lesion, including a small metastatic lesion. In follow-up laparoscopic hepatectomy, SHIFT-ICG could clearly and precisely image the full tumor regions and boundaries in real time, and even indistinguishable satellite lesions still expressed a remarkable fluorescence intensity. In conclusion, the simple and green SHIFT-ICG formulation can be effectively used in emergency embolization hemostasis and later precise fluorescence navigation hepatectomy in patients with ruptured HCC bleeding and has high clinical application value.

Urbanization alters soil bacterial communities in southern China coastal cities.

Urbanization carries essential influences to ecosystem of soil bacteria in coastal cities. Comprehending the patterns and drivers of bacterial diversity are essential to understanding how soil ecosystems respond to environmental change. This study aimed to explore how soil bacterial community (SBC) response to distinct urbanization of coastal cities on composition, assembly process and potential function in Guangdong province, south China. 72 samples from 24 sample sites within 3 cities were included in the study. Soil chemical properties were analyzed, and the bacterial community were investigated by high-throughout sequencing. Proteobacteria and Acidobacteria were the main phyla. Assembly processes remained in stochastic processes and co-occurrence network of SBC kept stable, while urbanization altered SBC by influencing the dominant phyla. The indicators of communities in coastal city soils were the genera gamma_proteobacterium and beta_proteobacterium. Urbanized extent was the non-negligible factor which affected soil bacterial community, despite the total carbon was still the most vital. The impact of urbanization on bacterial communities might follow a non-linear pattern. Faprotax function prediction showed different urbanized coastal city soils share similar metabolic potential. Our study improved our understanding of the response of soil bacterial communities to urbanization in subtropical coastal cities and offered a useful strategy to monitor the ecology risk toward the soil under urbanization.

Developing and Testing a Model of Dynamic Changes in Work-School Conflict and Workplace Deviance Over Time.

Work-school conflict is a major stressor for many college students who have paid jobs while in college. Although work-school conflict experience is dynamic, the extant research has predominantly cast it and its consequences as between-person phenomena from a static perspective, ignoring its inherent temporal nature. As a result, little is known about the intra-individual changes in work-school conflict and their associated consequences as implied by the related theory. Drawing on the stressor-emotion model of counterproductive work behavior, we conducted a longitudinal weekly diary study to examine how work-school conflict change can predict changes in negative emotions and workplace deviance (i.e., the change-to-change effects). We also tested core self-evaluation, time management skill, and financial well-being as moderators of the proposed mediated relationship. Results from latent change score modeling showed that upward work-school conflict change had a positive relationship with upward workplace deviance change via upward changes in negative emotions. Further, time management skill and financial well-being weakened the indirect relationships between upward work-school conflict change and upward workplace deviance change. However, the moderating nature of core self-evaluation on the indirect relationship contrasted with our hypothesis. Implications for theory and future research are discussed along with implications for organizations and college institutions.

Environmental selection and evolutionary process jointly shape genomic and functional profiles of mangrove rhizosphere microbiomes.

Mangrove reforestation with introduced species has been an important strategy to restore mangrove ecosystem functioning. However, how such activities affect microbially driven methane (CH4), nitrogen (N), and sulfur (S) cycling of rhizosphere microbiomes remains unclear. To understand the effect of environmental selection and the evolutionary process on microbially driven biogeochemical cycles in native and introduced mangrove rhizospheres, we analyzed key genomic and functional profiles of rhizosphere microbiomes from native and introduced mangrove species by metagenome sequencing technologies. Compared with the native mangrove (Kandelia obovata, KO), the introduced mangrove (Sonneratia apetala, SA) rhizosphere microbiome had significantly (p < 0.05) higher average genome size (AGS) (5.8 vs. 5.5 Mb), average 16S ribosomal RNA gene copy number (3.5 vs. 3.1), relative abundances of mobile genetic elements, and functional diversity in terms of the Shannon index (7.88 vs. 7.84) but lower functional potentials involved in CH4 cycling (e.g., mcrABCDG and pmoABC), N2 fixation (nifHDK), and inorganic S cycling (dsrAB, dsrC, dsrMKJOP, soxB, sqr, and fccAB). Similar results were also observed from the recovered Proteobacterial metagenome-assembled genomes with a higher AGS and distinct functions in the introduced mangrove rhizosphere. Additionally, salinity and ammonium were identified as the main environmental drivers of functional profiles of mangrove rhizosphere microbiomes through deterministic processes. This study advances our understanding of microbially mediated biogeochemical cycling of CH4, N, and S in the mangrove rhizosphere and provides novel insights into the influence of environmental selection and evolutionary processes on ecosystem functions, which has important implications for future mangrove reforestation.

Successful application of indocyanine green fluorescent imaging for the non-invasive detection of postoperative bile leakage.

There is a lack of a simple and reliable method for the diagnosis of postoperative bile leakage. ICG is a water-soluble fluorescent contrast agent. After intravenous injection of ICG, ICG is eventually excreted only through the biliary tract system into the intestines. It is highly sensitive, stable and nonradioactive, and these characteristics provide a theoretical basis for using ICG to diagnose postoperative bile leakage. Two patients with postoperative bile leakage were successfully identified using indocyanine green fluorescent imaging for the first time, suggesting its potential to be a convenient and reliable method for the diagnosis of postoperative bile leakage.

Immune checkpoint inhibitor-induced colitis complicated with inflammatory intestinal obstruction: a case report and literature review.

Background: The combination therapy using anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) has an excellent safety profile and manageable toxicity. However, ICI therapy may lead to a variety of autoimmune events, known as immune-related adverse events (irAEs), which some secondary complications may occur, such as immune-mediated colitis (IMC) and secondary inflammatory intestinal obstruction. It could impact clinical assessments and treatment decisions. Although there are few reports about secondary inflammatory intestinal obstruction related IMC. Case Description: We report an adult patient who suffered from primary liver cancer, who accepted ICIs (sintilimab) combined with vascular endothelial growth factor (VEGF) inhibitor (bevacizumab). He suffered worsening diarrhea about 5 days following immunotherapy. Computed tomography (CT) revealed the thickening intestinal wall of colon and rectum and massive cerebral gas in the proximal colon cavity. He was hospitalized with a diagnosis of IMC and inflammatory intestinal obstruction. Finally, he underwent the therapeutic option using combined glucocorticoid and somatostatin. His symptoms eased within 3 weeks and he was discharged from the hospital. Conclusions: IMC with diarrhea as the main manifestation requires early diagnosis and timely treatment. If the condition progresses, inflammatory intestinal obstruction may occur and this is a life-threatening situation. It is effective to accept early glucocorticoid and somatostatin while casual surgery may aggravate intestinal inflammation and injury, even death.

First case report of spontaneous biliary pleural fistula diagnosed using near infrared region I/II fluorescence of indocyanine green.

We report a rare case of spontaneous biliary pleural fistula in a patient whose diagnosis was aided by the use of near-infrared I/II fluorescence imaging. When both 99mTc-mebrofenin hepatobiliary scintigraphy and CT examination were diagnostically difficult, we found strong fluorescent signals in the patient's pleural drainage fluid and sputum using NIR I/II fluorescence imaging, and therefore diagnosed the patient with a biliary pleural fistula. This provides a safe and effective test for diagnosing biliary pleural fistulas.

A new precise way to guide the debridement process of diabetic foot ulcer using indocyanine green fluorescence molecular imaging.

OBJECTIVE: The purpose of this study was to estimate the value of a novel imaging technique in necrotic tissue debridement of diabetic foot ulcers (DFU), using near-infrared (NIR) fluorescence molecular imaging (FMI) of indocyanine green (ICG). METHODS: The patients with DFU were included and divided into a FMI navigation debridement group and a traditional group. The FMI of the wounds and the debridement effect of each group was analyzed, including debridement frequency, length of hospital stay, and the histological examination of removed tissue. RESULT: A total of 40 patients with DFU (23 cases in the FMI group and 17 cases in the traditional group) were included in this study. The positive rate of wound fluorescence in the FMI group was 96%, and no patients had related side effects. The pathological examination confirmed that the tissue emitting NIR fluorescence was totally necrotic tissue. In addition, the debridement frequency in the FMI group is less than that in the traditional group, but there is no difference in the length of hospital stay between the two groups. CONCLUSION: ICG FMI technique can accurately illuminated necrotic tissue, with high sensitivity, easy operation and good safety, which would be a new way to precisly guide the process of debridement in the clinic.

The hidden performance costs of professional isolation? A latent change score model of professional isolation during the early stage of COVID-19 pandemic.

Although past research has found that professional isolation can affect discernible work-related outcomes (e.g. job performance and turnover) and important job attitudes, researchers have not examined its impact on those less discernible but still costly work behaviours. Drawing on self-regulation theories, this study examined the effect of professional isolation on employees' cyberloafing and time theft through self-control capacity impairment. With longitudinal data collected from 343 U.S. employees across five consecutive weeks at the early stage of the pandemic (i.e. from mid-March to late April 2020), our results of latent change score modelling analyses found that professional isolation change was positively related with changes in cyberloafing and time theft via change in self-control capacity impairment. The results increase our understanding of the hidden performance cost of professional isolation. This research also shifts the research focus from a static, between-person perspective to dynamic, within-person changes in professional isolation and related outcomes. The findings shed light on the self-regulation perspective in understanding the harmful consequences of professional isolation. Implications for future research are discussed along with practical implications for organisations.

Effectiveness of radiofrequency ablation versus transarterial chemoembolization for recurrent hepatocellular carcinoma: A meta-analysis.

Background: Both transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective methods for the treatment of recurrent hepatocellular carcinoma (RHCC). Thus far, it is unclear which method is more satisfactory in short- and long-term survival benefits. Purpose: To compare the overall survival (OS) and complications of TACE and RFA used for the management of RHCC. Material and Methods: A literature search was carried out using PubMed, the Cochrane Library and, Embase databases, and Google Scholar, keywords including "RHCC," "TACEC," and "RFA" with a cutoff date of 30 April 2021. Used Review Manager software was to calculate short- and long-term OS. The clinical outcomes are major complications and complete response (CR). Results: Finally, nine clinical trials met the research standard, including 1326 subjects, of which 518 received RFA and 808 received TACE. The analysis showed that patients who underwent RFA had significantly higher 1-, 3-, and 5-year OS (OR1-year = 1.92, 95% confidence interval (CI) = 1.27-2.91, p = .002; OR3-year = 1.64, 95% CI = 1.30-2.08, p <.0001; OR5-year = 3.22, 95% CI = 1.34-7.72, p=.009). Besides, the patients who chose RFA had an obvious higher rate of CR than those receiving TACE (OR = 33.75, 95% CI = 1.73-658.24, p = .002). However, the major complications were consistency between these two groups. Conclusion: Our study discovered that RFA had greater CR and incidence in both the short-term and long-term OS than TACE. In addition, obvious difference was not found in major complications in these two methods.