Biophilic Positive Carbon Dot Exerts Antifungal Activity and Augments Corneal Permeation for Fungal Keratitis.

Fungal keratitis (FK) is an infectious eye disease that poses a significant risk of blindness. However, the effectiveness of conventional antifungal drugs is limited due to the intrinsic ocular barrier that impedes drug absorption. There is an urgent need to develop new therapeutic strategies to effectively combat FK. Herein, we synthesized an ultrasmall positively charged carbon dot using a simple stage-melting method. The carbon dot can penetrate the corneal barrier by opening the tight junctions, allowing them to reach the lesion site and effectively kill the fungi. The results both in vitro and in vivo demonstrated that it exhibited good biocompatibility and antifungal activity, significantly improving the therapeutic effect in a mouse model of FK. Therefore, this biophilic ultrasmall size and positive carbon dot, characterized by its ability to penetrate the corneal barrier and its antifungal properties, may offer valuable insights into the design of effective ocular nanomedicines.

Ts2O Promoted Deoxygenative C-H Dithiocarbonation of Quinoline N-Oxides with Potassium O-Alkyl Xanthates.

A simple, efficient, and practical method for the synthesis of S-quinolyl xanthates was developed via Ts2O-promoted deoxygenative C-H dithiocarbonation of quinoline N-oxides with various potassium O-alkyl xanthates. The reaction performed well under transition-metal-free, base-free, and room-temperature conditions with wide substrate tolerance. Employing potassium O-tert-butyl xanthate (tBuOCS2K) as a nucleophile, some valuable quinoline-2-thiones were unexpectedly obtained in a one-pot reaction without any additional base.

Dual-ROS-scavenging and dual-lingering nanozyme-based eye drops alleviate dry eye disease.

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings.

Persulfate-Promoted Carbamoylation/Cyclization of Alkenes: Synthesis of Amide-Containing Quinazolinones.

The incorporation of amide groups into biologically active molecules has been proven to be an efficient strategy for drug design and discovery. In this study, we present a simple and practical method for the synthesis of amide-containing quinazolin-4(3H)-ones under transition-metal-free conditions. This is achieved through a carbamoyl-radical-triggered cascade cyclization of N3-alkenyl-tethered quinazolinones. Notably, the carbamoyl radical is generated in situ from the oxidative decarboxylative process of oxamic acids in the presence of (NH4)2S2O8.

Ball milling synthesis of S-quinolyl xanthates via coupling of haloquinolines with potassium O-alkyl xanthates.

An environmentally benign protocol that provides various S-quinolyl xanthates via a ball milling enabled cross coupling reaction of haloquinolines and readily available potassium O-alkyl xanthates is first reported. The reaction proceeded well under mild, transition metal- and solvent-free conditions, making it an attractive method for the introduction of xanthates into the quinoline scaffold.

Regulation of tourmaline-mediated Fenton-like system by biochar: Free radical pathway to non-free radical pathway.

The heterogeneous Fenton-like systems induced by Fe-containing minerals have been largely applied for the degradation of organic pollutants. However, few studies have been conducted on biochar (BC) as an additive to Fenton-like systems mediated by iron-containing minerals. In this study, the addition of BC prepared at different temperatures was found to significantly enhance the degradation of contaminants in the tourmaline-mediated Fenton-like system (TM/H2O2) using Rhodamine B (RhB) as the target contaminant. Furthermore, the hydrochloric acid-modified BC prepared at 700 °C (BC700(HCl)) could achieve complete degradation of high concentrations of RhB in the BC700(HCl)/TM/H2O2 system. Free radical quenching experiments showed that TM/H2O2 system removed contaminants mainly mediated by the free radical pathway. After adding BC, the removal of contaminants is mainly mediated by the non-free radical pathway in BC700(HCl)/TM/H2O2 system which was confirmed by the Electron paramagnetic resonance (EPR) experiments and electrochemical impedance spectroscopy (EIS). In addition, BC700(HCl) had broad feasibility in the degradation of other organic pollutants (Methylene Blue (MB) 100%, Methyl Orange (MO) 100%, and tetracycline (TC) 91.47%) in the tourmaline-mediated Fenton-like system. Possible pathways for the degradation of RhB by the BC700(HCl)/TM/H2O2 system were also proposed.

A direct negative feedback loop of miR-4721/FOXA1/Nanog promotes nasopharyngeal cell stem cell enrichment and metastasis.

OBJECTIVE: The recurrence and metastasis of nasopharyngeal cancer (NPC) may be mainly attributed to the persistence of cancer stem cells (CSCs); however, the linkage mechanism has yet to be fully elucidated. METHODS: The levels of miR-4721, FOXA1, and Nanog expression in NPC were detected by in situ hybridization and immunohistochemistry. In vivo and in vitro metastasis assays confirmed miR-4721 promotes cell migration and invasion. Tumor spheroid formation assay, side population (SP) assay, and ALDEFLUOR assay verified miR-4721 regulates cancer stem cell-like properties. Luciferase reporter assay showed that miR-4721 directly regulates FOXA1 and FOXA1 effects the promoter activity of miR-4721 and Nanog. Chromatin immunoprecipitation (ChIP) analysis and electrophoresis mobility shift assay (EMSA) revealed that FOXA1 combined the promoter region of human miR-4721 and Nanog and the possible mechanism was also analyzed. RESULTS: In this study, a new mechanism of NPC tumorigenesis related to miR-4721 was verified. We found that miR-4721, FOXA1 and Nanog control their expressions through a negative feedback loop and then activate the downstream regulator of stem cell signaling to promote the enrichment and metastasis of NPC stem cells. CONCLUSION: These findings elucidate that the feedback loop of miR-4721/FOXA1/Nanog can regulate stemness and metastasis in NPC and may provide an experimental theoretical basis for metastasis and treatment resistance in NPC.

VPS33B negatively modulated by nicotine functions as a tumor suppressor in colorectal cancer.

The biological role of vacuolar protein sorting 33B (VPS33B) has not been examined in colorectal cancer (CRC). We report that VPS33B was downregulated in dextran sulfate sodium/azoxymethane (DSS/AOM) -induced CRC mice models and nicotine-treated CRC cells via the PI3K/AKT/c-Jun pathway. Reduced VPS33B is an unfavorable factor promoting poor prognosis in human CRC patients. VPS33B overexpression suppressed CRC proliferation, intrahepatic metastasis and chemoresistance of cisplatin (DDP) in vivo and in vitro through modulating the epidermal growth factor receptor (EGFR)/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop and the downstream cell cycle or EMT-related factors. Furthermore, NESG1 as a newly identified tumor suppressor interacted with VPS33B via colocalization in the cytoplasm, and it was stimulated by VPS33B through the downregulation of RAS/ERK/c-Jun-mediated transcription. NESG1 also activated VPS33B expression via the RAS/ERK/c-Jun pathway. Suppression of NESG1 increased cell growth, migration and invasion via the reversion of the VPS33B-modulating signal in VPS33B-overexpressed cells. Taken together, VPS33B as a tumor suppressor is easily dysregulated by chemical carcinogens and it interacts with NESG1 to modulate the EGFR/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop and thus suppress the malignant phenotype of CRC.

Diagnostic Roles of Postmortem cTn I and cTn T in Cardiac Death with Special Regard to Myocardial Infarction: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Cardiac troponin I (cTn I) and cardiac troponin T (cTn T) are currently widely used as diagnostic biomarkers for myocardial injury caused by ischemic heart diseases in clinical and forensic medicine. However, no previous meta-analysis has summarized the diagnostic roles of postmortem cTn I and cTn T. The aim of the present study was to meta-analyze the diagnostic roles of postmortem cTn I and cTn T for cardiac death in forensic medicine, present a systematic review of the previous literature, and determine the postmortem cut-off values of cTn I and cTn T. METHODS: We searched multiple databases for the related literature, performed a meta-analysis to investigate the diagnostic roles of postmortem cardiac troponins, and analyzed the receiver operating characteristic (ROC) curve to determine their postmortem cut-off values. RESULTS AND CONCLUSIONS: The present meta-analysis demonstrated that postmortem cTn I and cTn T levels were increased in pericardial fluid and serum in cardiac death, especially in patients with acute myocardial infarction (AMI). We determined the postmortem cut-off value of cTn I in the pericardial fluid at 86.2 ng/mL, cTn I in serum at 9.5 ng/mL, and cTn T in serum at 8.025 ng/mL.

miR-16 induction after CDK4 knockdown is mediated by c-Myc suppression and inhibits cell growth as well as sensitizes nasopharyngeal carcinoma cells to chemotherapy.

Cyclin-dependent kinase 4 (CDK4) is a member of cyclin-dependent kinase family which regulates G1 to S cell cycle transition. CDK4 activity is increased in many tumor types. Here, we report a negative automodulatory feedback loop between CDK4 and miR-16 that regulates cell cycle progression in nasopharyngeal carcinoma (NPC). By miRNA array and real-time PCR, we identified upregulation of tumor suppressor miR-16a, which inhibited cell cycle progression and sensitized NPC cells to chemotherapy. CDK4 knockdown reduced the expression of c-Myc, the latter of which directly suppresses the miR-16 expression by directly binding to the miR-16 promoter. Moreover, we found that miR-16 upregulation could reduce CDK4 expression by repressing CCND1 and thus forms a feedback loop via the CDK4/c-Myc/miR-16/CCND1 pathway. Finally, miR-16 was negatively correlated with CDK4 expression in NPC biopsies. In summary, our results define a double-negative feedback loop involving CDK4 and miR-16 mediated by c-Myc that modulates NPC cell growth and chemotherapy sensitivity.

Dual-Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease.

Dry eye disease (DED) is a major ocular pathology worldwide, causing serious ocular discomfort and even visual impairment. The incidence of DED is gradually increasing with the high-frequency use of electronic products. Although inflammation is core cause of the DED vicious cycle, reactive oxygen species (ROS) play a pivotal role in the vicious cycle by regulating inflammation from upstream. Therefore, current therapies merely targeting inflammation show the failure of DED treatment. Here, a novel dual-atom nanozymes (DAN)-based eye drops are developed. The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer. The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS, inhibiting NLRP3 inflammasome activation, decreasing proinflammatory cytokines expression, and suppressing cell apoptosis. Consequently, the DAN effectively alleviate ocular inflammation, promote corneal epithelial repair, recover goblet cell density and tear secretion, thus breaking the DED vicious cycle. Our findings open an avenue to make the DAN as an intervention form to DED and ROS-mediated inflammatory diseases.

Circadian metabolites for evaluating the timing of bloodstain deposition: A preliminary study.

Metabolites, as products of cellular metabolism, can provide a wealth of biological information and are less susceptible to degradation than other biomarkers due to their low molecular weight. Due to these properties, metabolites can be used as valuable biomarkers for forensic investigations. Knowing the timing of deposition of bloodstain could help to reconstruct crime scenes, draw conclusions about the time of the crime, and narrow down the circle of possible suspects. Previous studies have indicated that the concentration of some metabolites in blood is subject to circadian changes. However, the circadian metabolites of bloodstains have been still unclear. A total of sixty-four bloodstain samples were prepared under real conditions in three time categories (morning/noon (09:00 h ∼ 17:00 h), afternoon/evening (18:00 h ∼ 23:00 h) and night/early morning (24:00 h ∼ 08:00 h)). Fifty metabolites of bloodstains with significant differences were identified in the three time categories. Twenty-eight of these metabolites exhibited significant circadian changes. Finally, three independently contributing circadian metabolites were selected to build the logistic regression model, with an area under the curve of 0.91, 0.84 and 0.87 for the prediction of bloodstain deposition time in the morning/noon, afternoon/evening and night/early morning, respectively. The study indicated that circadian metabolites can be used for evaluating the timing of bloodstain deposition. This would provide a valuable perspective for analyzing the deposition time of biological traces in forensic investigations.

Immobilization of Pb in waste water and soil by tourmaline-biochar composites (TBs): Characteristics and mechanisms.

Novel tourmaline-biochar composites (TBs) were synthesized by introducing tourmaline (TM) into pomelo peel biochar (BC). The surface properties of TBs and BC were studied and the adsorption performances for Pb2+ were investigated. Compared to pristine BC, the adsorption ability for Pb2+ on TBs was enhanced with the increase of TM in TBs, and up to 514.62 mg/g on 5%TB. The enrichment of inorganic metals caused by TM in TBs made the precipitation and cation ion exchange become the main mechanisms in adsorbing Pb2+, and the amounts of adsorbing Pb2+ by those two mechanisms on TBs were 1.10-1.48 times and 1.20-1.30 times those of BC, respectively. Furthermore, applying TBs to practical contaminated soil increased the soil pH and electrical conductivity (EC) after 15 days of incubation. The increased content of residual-Pb and reduced exchangeable-Pb and DTPA-Pb indicated that TBs were favorable for the immobilization of Pb in soil. This study gives a new perspective on the synthesis of tourmaline-biochar composite and their application in Pb-polluted water and soil.

How Green Mindfulness and Green Shared Vision Interact to Influence Green Creative Behavior.

Aim: The study is based on the self-determination theory and aims to investigate the mediating role of green intrinsic motivation and the moderating role of green shared vision in the association between frontline managers' green mindfulness and green creative behavior to leverage their capacity to think creatively and act sustainably. Methods: The study employs a time-lagged, multi-source research methodology to collect data from frontline managers of service businesses in the tourism and hospitality industry. Data are analyzed using SmartPLS Structural Equation Model to evaluate the structural and measurement models. The authors evaluated the measurement model by employing the criteria of internal consistency: reliability and Cronbach's alpha, validity: convergent and discriminant validity; and the structural model using the path coefficient, coefficient of determination, predictive relevance, and goodness-of-fit metrics. Results: Our findings indicate that green mindfulness significantly improves frontline managers' green creative behavior. Additionally, green intrinsic motivation mediates the connection between green mindfulness and green creative behavior. In addition, the direct effect of green mindfulness on green intrinsic motivation as well as the indirect effect of green mindfulness on green creative behavior through green intrinsic motivation, are both significantly moderated by green shared vision. Discussion: To the best of the authors' knowledge, this is one of the few efforts that outstretch the boundary conditions of green mindfulness and green creative behavior through the mediating role of green intrinsic motivation and the moderating role of green shared vision.

Stable tissue-mimicking phantoms for longitudinal multimodality imaging studies that incorporate optical, CT, and MRI contrast.

Significance: Tissue phantoms that mimic the optical and radiologic properties of human or animal tissue play an important role in the development, characterization, and evaluation of imaging systems. Phantoms that are easily produced and stable for longitudinal studies are highly desirable. Aim: A new type of long-lasting phantom was developed with commercially available materials and was assessed for fabrication ease, stability, and optical property control. Magnetic resonance imaging (MRI) and x-ray computed tomography (CT) contrast properties were also evaluated. Approach: A systematic investigation of relationships between concentrations of skin-like pigments and composite optical properties was conducted to realize optical property phantoms in the red and near-infrared (NIR) wavelength range that also offered contrast for CT and MRI. Results: Phantom fabrication time was < 1 h and did not involve any heating or cooling processes. Changes in optical properties were < 2 % over a 12-month period. Phantom optical and spectral features were similar to human soft tissue over the red to NIR wavelength ranges. Pigments used in the study also had CT and MRI contrasts for multimodality imaging studies. Conclusions: The phantoms described here mimic optical properties of soft tissue and are suitable for multimodality imaging studies involving CT or MRI without adding secondary contrast agents.

Peroxidase-like MoS2/Ag nanosheets with synergistically enhanced NIR-responsive antibacterial activities.

Pathogenic microbial infections have been threatening public health all over the world, which makes it highly desirable to develop an antibiotics-free material for bacterial infection. In this paper, molybdenum disulfide (MoS2) nanosheets loaded with silver nanoparticles (Ag NPs) were constructed to inactive bacteria rapidly and efficiently in a short period under a near infrared (NIR) laser (660 nm) in the presence of H2O2. The designed material presented favorable features of peroxidase-like ability and photodynamic property, which endowed it with fascinating antimicrobial capacity. Compared with free MoS2 nanosheets, the MoS2/Ag nanosheets (denoted as MoS2/Ag NSs) exhibited better antibacterial performance against Staphylococcus aureus by the generated reactive oxygen species (ROS) from both peroxidase-like catalysis and photodynamic, and the antibacterial efficiency of MoS2/Ag NSs could be further improved by increasing the amount of Ag. Results from cell culture tests proved that MoS2/Ag3 nanosheets had a negligible impact on cell growth. This work provided new insight into a promising method for eliminating bacteria without using antibiotics, and could serve as a candidate strategy for efficient disinfection to treat other bacterial infections.

PINK1/Parkin-mediated mitophagy in neurodegenerative diseases.

Mitochondria play key roles in bioenergetics, metabolism, and signaling; therefore, stable mitochondrial function is essential for cell survival, particularly in energy-intensive neuronal cells. In neurodegenerative diseases, damaged mitochondria accumulate in neurons causing associated bioenergetics deficiency, impaired cell signaling, defective cytoplasmic calcium buffering, and other pathological changes. Mitochondrial quality control is an important mechanism to ensure the maintenance of mitochondrial health, homeostasis, and mitophagy, the latter of which is a pathway that delivers defective mitochondria to the lysosome for degradation. Defective mitophagy is thought to be responsible for the accumulation of damaged mitochondria, which leads to cellular dysfunction and/or death in neurodegenerative diseases. PINK1/Parkin mainly regulates ubiquitin-dependent mitophagy, which is crucial for many aspects of mitochondrial physiology, particularly the initiation of autophagic mechanisms. Therefore, in the present review, we summarize the current knowledge of the conventional mitophagy pathway, focusing on the molecular mechanisms underlying mitophagy dysregulation in prion disease and other age-related neurodegenerative diseases, especially in relation to the PINK1/Parkin pathway. Moreover, we list the inducers of mitophagy that possess neuroprotective effects, in addition to their mechanisms related to the PINK1/Parkin pathway. These mechanisms may provide potential interventions centered on the regulation of mitophagy and offer therapeutic strategies for the treatment of neurodegenerative diseases.

Elaborating the mechanism of lead adsorption by biochar: Considering the impacts of water-washing and freeze-drying in preparing biochar.

This paper examined the impacts of different pretreatments on the characteristics of biochar and its adsorption behavior for Pb2+. Biochar with combined pretreatment of water-washing and freeze-drying (W-FD-PB) performed a maximum adsorption capacity for Pb2+ of 406.99 mg/g, higher than that of 266.02 mg/g on water-washing pretreated biochar (W-PB) and 188.21 mg/g on directly pyrolyzed biochar (PB). This is because the water-washing process partially removed the K and Na, resulting in the relatively enriched Ca and Mg on W-FD-PB. And the freeze-drying pretreatment broke the fiber structure of pomelo peel, favoring the development of a fluffy surface and large specific surface area during pyrolysis. Quantitative mechanism analysis implied that cation ion exchange and precipitation were the driving forces in Pb2+ adsorption on biochar, and both mechanisms were enhanced during Pb2+ adsorption on W-FD-PB. Furthermore, adding W-FD-PB to Pb-contaminated soil increased the soil pH and significantly reduced the availability of Pb.

Recent Advances in Thallium Removal from Water Environment by Metal Oxide Material.

Thallium is widely used in industrial and agricultural development. However, there is still a lack of systematic understanding of its environmental hazards and related treatment methods or technologies. Here, we critically assess the environmental behavior of thallium in aqueous systems. In addition, we first discuss the benefits and limitations of the synthetic methods of metal oxide materials that may affect the practicality and scalability of TI removal from water. We then assess the feasibility of different metal oxide materials for TI removal from water by estimating the material properties and contaminant removal mechanisms of four metal oxides (Mn, Fe, Al, and Ti). Next, we discuss the environmental factors that may inhibit the practicality and scalability of Tl removal from water. We conclude by highlighting the materials and processes that could serve as more sustainable alternatives to TI removal with further research and development.

Estimation of bloodstain deposition time within a 24-h day-night cycle with rhythmic mRNA based on a machine learning algorithm.

Estimating the time that bloodstains are left at a crime scene can provide invaluable evidence for law enforcement investigations, including determining the time of the crime, linking the perpetrator to the crime scene, narrowing the pool of possible suspects, and verifying witness statements. There have been some attempts to estimate the time since deposition of bloodstains, i.e., how much time has passed since the bloodstain was left at a crime scene. However, most studies focus on the time interval of days. As far as we know, previous study have been conducted to estimate the deposition time of blood within a 24-h day-night cycle. To date, there is a lack of studies on whether rhythmic mRNA of blood is suitable for bloodstain samples. In this study, we estimated the bloodstain deposition time within a 24-h day-night cycle based on the expression of messenger RNAs (mRNAs) by real-time quantitative polymerase chain reaction. Bloodstain samples were prepared from eight individuals at eight time points under real and uncontrolled conditions. Four mRNAs expressed rhythmically and were used to construct a regression model using the k-nearest neighbor (KNN) algorithm, resulting in a mean absolute error of 3.92 h. Overall, using the rhythmic mRNAs, a machine learning model was developed which has allowed us to predict the deposition time of bloodstains within the 24-h day-night cycle in East Asian populations. This study demonstrates that mRNA biomarkers can be used to estimate the bloodstain deposition time within a 24-h period. Furthermore, rhythmic mRNA biomarkers provide a potential method and perspective for estimating the deposition time of forensic traces in forensic investigation. Case samples in forensic analysis are usually limited or degraded, so the stability and sensitivity of rhythmic biomarkers need to be further investigated.