An acid-free sensing strategy for detecting nitrite using dihydroquinoline-8-carboxylate as a probe.

Nitrite (NO2-) has been identified as a typical pollutant harmful to the human body and heavily assayed in the fields of food safety and water quality control. The mainstream sensing strategies for detecting NO2- depend on Griess reaction or its improved methods which employ Griess reaction to initiate further inter-or intramolecular interaction to generate readout signals. However, a significant drawback of these methods is the use of strongly acidic media. In this study, we designed and synthesized a new NO2--specific fluorescent probe (ethyl 3-cyano-2-hydroxy-5-imino-8-(3-methoxy-3-oxopropyl)-4-(pyridin-2-yl)-5,8-dihydroquinoline-8-carboxylate, DHQC). DHQC exhibited strong green fluorescence in an acetonitrile-PBS (10 mM) mixed system (pH 7.0). In the neutral medium and at room temperature, the fluorescence of DHQC changed from green to blue with the addition of NO2-. The preliminary mechanistic investigation reveals that NO2- can induce the decarboxylation of the probe DHQC. Based on this finding, a high sensitive and selective method for NO2--detection was established, which showed good linearity in a range of 5∼50 µM with a limit detection of 3.5 nM (3σ). Given the unique properties of DHQC, a DHQC-loaded hydrogel bead device was further developed and employed for rapid monitoring of NO2-, exhibiting the advantages of simple preparation, high sensitivity, and fast response compared with traditional sensing reagents. In addition, DHQC was also used as a fluorescent probe for cell-imaging in live cells, exhibiting good cell permeability and biocompatibility. This study proposes a potential strategy for constructing smart fluorimetric probes used for NO2- detection.

Joint use of population pharmacokinetics and machine learning for prediction of valproic acid plasma concentration in elderly epileptic patients.

BACKGROUND: Valproic acid (VPA) is a commonly used broad-spectrum antiepileptic drug. For elderly epileptic patients, VPA plasma concentrations have a considerable variation. We aim to establish a prediction model via a combination of machine learning and population pharmacokinetics (PPK) for VPA plasma concentration. METHODS: A retrospective study was performed incorporating 43 variables, including PPK parameters. Recursive Feature Elimination with Cross-Validation was used for feature selection. Multiple algorithms were employed for ensemble model, and the model was interpreted by Shapley Additive exPlanations. RESULTS: The inclusion of PPK parameters significantly enhances the performance of individual algorithm model. The composition of categorical boosting, light gradient boosting machine, and random forest (7:2:1) with the highest R2 (0.74) was determined as the ensemble model. The model included 11 variables after feature selection, of which the predictive performance was comparable to the model that incorporated all variables. CONCLUSIONS: Our model was specifically tailored for elderly epileptic patients, providing an efficient and cost-effective approach to predict VPA plasma concentration. The model combined classical PPK with machine learning, and underwent optimization through feature selection and algorithm integration. Our model can serve as a fundamental tool for clinicians in determining VPA plasma concentration and individualized dosing regimens accordingly.

Parameterized Multipartite Entanglement and Genuine Entanglement Measures Based on q-Concurrence.

We study genuine multipartite entanglement (GME) and multipartite k-entanglement based on q-concurrence. Well-defined parameterized GME measures and measures of multipartite k-entanglement are presented for arbitrary dimensional n-partite quantum systems. Our GME measures show that the GHZ state is more entangled than the W state. Moreover, our measures are shown to be inequivalent to the existing measures according to entanglement ordering. Detailed examples show that our measures characterize the multipartite entanglement finer than some existing measures, in the sense that our measures identify the difference of two different states while the latter fail.

Applying the six-sigma methodology to determine the limits of quality control (QC) tests for a specific linear accelerator.

PURPOSE: We aimed to show the framework of the six-sigma methodology (SSM) that can be used to determine the limits of QC tests for the linear accelerator (Linac). Limits for QC tests are individually determined using the SSM. METHODS AND MATERIALS: The SSM is based on the define-measure-analyze-improve-control (DMAIC) stages to improve the process. In the "define" stage, the limits of QC tests were determined. In the "measure" stage, a retrospective collection of daily QC data using a Machine Performance Check platform was performed from January 2020 to December 2022. In the "analyze" stage, the process of determining the limits was proposed using statistical analyses and process capability indices. In the "improve" stage, the capability index was used to calculate the action limits. The tolerance limit was established using the larger one of the control limits in the individual control chart (I-chart). In the "control" stage, daily QC data were collected prospectively from January 2023 to May 2023 to monitor the effect of action limits and tolerance limits. RESULTS: A total of 798 sets of QC data including beam, isocenter, collimation, couch, and gantry tests were collected and analyzed. The Collimation Rotation offset test had the min-Cp, min-Cpk, min-Pp, and min-Ppk at 2.53, 1.99, 1.59, and 1.25, respectively. The Couch Rtn test had the max-Cp, max-Cpk, max-Pp, and max-Ppk at 31.5, 29.9, 23.4, and 22.2, respectively. There are three QC tests with higher action limits than the original tolerance. Some data on the I-chart of the beam output change, isocenter KV offset, and jaw X1 exceeded the lower tolerance and action limit, which indicated that a system deviation occurred and reminded the physicist to take action to improve the process. CONCLUSIONS: The SSM is an excellent framework to use in determining the limits of QC tests. The process capability index is an important parameter that provides quantitative information on determining the limits of QC tests.

Synergistic effects of silicon and goethite co-application in alleviating cadmium stress in rice (Oryza sativa L.): Insights into plant growth and iron plaque formation mechanisms.

Rice is one of the most important staple food crops; however, it is prone to cadmium (Cd) accumulation, which has negative health effects. Therefore, methods to reduce Cd uptake by rice are necessary. At present, there is limited research on the effects of co-application of silicon (Si) and goethite in mitigating Cd stress in rice. Furthermore, the specific mechanisms underlying the effects of their combined application on iron plaque formation in rice roots remain unclear. Therefore, this study analyzed the effects of the combined application of Si and goethite on the biomass, physiological stress indicators, Cd concentration, and iron plaques of rice using hydroponic experiments. The results revealed that co-treatment with both Si and goethite increased the plant height and dry weight, superoxide dismutase and catalase activities, photosynthetic pigment concentration, and root activity. Moreover, this treatment decreased the malondialdehyde concentration, repaired epidermal cells, reduced the Cd concentration in the roots by 57.2 %, and increased the number of iron plaques and Cd concentration by 150.9 % and 266.2 % in the amorphous and crystalline fractions, respectively. The Cd/Fe ratio in amorphous iron plaques also increased. Our findings suggest that goethite serves as a raw material for iron plaque formation, while Si enhances the oxidation capacity of rice roots. The application of a combination of Si and goethite increases the quantity and quality of iron plaques, enhancing its Cd fixation capacity. This study provides theoretical evidence for the effective inhibition of Cd uptake by iron plaques in rice, providing insights into methods for the remediation of Cd contamination.

Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients.

BACKGROUND: The understanding of bile acid (BA) and unsaturated fatty acid (UFA) profiles, as well as their dysregulation, remains elusive in individuals with type 2 diabetes mellitus (T2DM) coexisting with non-alcoholic fatty liver disease (NAFLD). Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM. AIM: To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM. METHODS: A training model was developed involving 399 participants, comprising 113 healthy controls (HCs), 134 individuals with T2DM without NAFLD, and 152 individuals with T2DM and NAFLD. External validation encompassed 172 participants. NAFLD patients were divided based on liver fibrosis scores. The analytical approach employed univariate testing, orthogonal partial least squares-discriminant analysis, logistic regression, receiver operating characteristic curve analysis, and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers. RESULTS: Compared to HCs, both T2DM and NAFLD groups exhibited diminished levels of specific BAs. In UFAs, particular acids exhibited a positive correlation with NAFLD risk in T2DM, while the ω-6:ω-3 UFA ratio demonstrated a negative correlation. Levels of α-linolenic acid and γ-linolenic acid were linked to significant liver fibrosis in NAFLD. The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients. CONCLUSION: This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM, proposing their potential as biomarkers in the pathogenesis of NAFLD.

Crack Formation and Control in an AlCoCrFeNi High Entropy Alloy Fabricated by Selective Laser Melting.

The equiatomic AlCoCrFeNi high entropy alloy (HEA) is prone to cracking during the additive manufacturing process due to the high cooling rates observed, which limits its application to a large extent. In this study, the selective laser melting (SLM) technique was adopted to fabricate the alloy and the mechanism of crack formation was revealed. Most importantly, a new design strategy was proposed to suppress the generation of cracks, and the optimization of the preparation process was also studied in detail. It is found that the interlaminar crack is related to the heat input at the edge of the specimen, and the internal cracks are formed by solidification cracks. Alloys without interlaminar crack can be prepared by means of combination of the side inclination angle and the process parameters. Side inclination angle optimization provides a possibility for the preparation of crack-free AlCoCrFeNi HEA by SLM.

Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway.

BACKGROUND: Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved. Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process. AIM: To assess the influence of interleukin-10 (IL-10) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) following their interaction with macrophages in an inflammatory environment. METHODS: IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment. In this study, we investigated its impact on the proliferation, migration, and osteogenesis of BMSCs. The expression levels of signal transducer and activator of transcription 3 (STAT3) and its activated form, phosphorylated-STAT3, were examined in IL-10-stimulated macrophages. Subsequently, a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling. RESULTS: IL-10-stimulated macrophages underwent polarization to the M2 type through substitution, and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs. Mechanistically, STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages. Specifically, IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response, as evidenced by its diminished impact on the osteogenic differentiation of BMSCs. CONCLUSION: Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs. The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs' osteogenic differentiation.

CD40 is an immune checkpoint regulator that potentiates myocardial inflammation through activation and expansion of CCR2 + macrophages and CD8 T-cells.

Novel immune checkpoint therapeutics including CD40 agonists have tremendous promise to elicit antitumor responses in patients resistant to current therapies. Conventional immune checkpoint inhibitors (PD-1/PD-L1, CTLA-4 antagonists) are associated with serious adverse cardiac events including life-threatening myocarditis. However, little is known regarding the potential for CD40 agonists to trigger myocardial inflammation or myocarditis. Here, we leveraged genetic mouse models, single cell sequencing, and cell depletion studies to demonstrate that an anti-CD40 agonist antibody reshapes the cardiac immune landscape through activation of CCR2 + macrophages and subsequent recruitment of effector memory CD8 T-cells. We identify a positive feedback loop between CCR2 + macrophages and CD8 T-cells driven by IL12b, TNF, and IFN-γ signaling that promotes myocardial inflammation and show that prior exposure to CD40 agonists sensitizes the heart to secondary insults and accelerates LV remodeling. Collectively, these findings highlight the potential for CD40 agonists to promote myocardial inflammation and potentiate heart failure pathogenesis.

Analysis of spinal muscular atrophy carrier screening results in 32,416 pregnant women and 7,231 prepregnant women.

Objectives: Spinal muscular atrophy (SMA) is an autosomal recessive disease that is one of the most common in childhood neuromuscular disorders. Our screenings are more meaningful programs in preventing birth defects, providing a significant resource for healthcare professionals, genetic counselors, and policymakers involved in designing strategies to prevent and manage SMA. Method: We screened 39,647 participants from 2020 to the present by quantitative real-time PCR, including 7,231 pre-pregnancy participants and 32,416 pregnancy participants, to detect the presence of SMN1 gene EX7 and EX8 deletion in the DNA samples provided by the subjects. To validate the accuracy of our findings, we also utilized the Multiplex Ligation-dependent Probe Amplification (MLPA) to confirm the reliability of screening results obtained by quantitative real-time PCR. Result: Among the 39,647 participants who were screened, 726 participants were the carriers of SMN1. The overall carrier rate was calculated to be 1.83% (95% confidence interval: 0.86-2.8%). After undergoing screening, a total of 592 pregnancy carriers were provided with genetic counseling and only 503 of their spouses (84.97, 95% confidence interval: 82.09-87.85%) voluntarily underwent SMA screening. Conclusion: This study provides crucial insights into the prevalence and distribution of SMA carriers among the female population. The identification of 726 asymptomatic carriers highlights the necessity of comprehensive screening programs to identify at-risk individuals and ensure appropriate interventions are in place to minimize the impact of SMA-related conditions.

Biomechanical analysis of the maxillary sinus floor membrane during internal sinus floor elevation with implants at different angles of the maxillary sinus angles.

OBJECTIVE: This study analyzed and compared the biomechanical properties of maxillary sinus floor mucosa with implants at three different maxillary sinus angles during a modified internal sinus floor elevation procedure. METHODS: 3D reconstruction of the implant, maxillary sinus bone, and membrane were performed. The maxillary sinus model was set at three different angles. Two internal maxillary sinus elevation models were established, and finite element analysis was used to simulate the modified maxillary sinus elevation process. The implant was elevated to 10 mm at three maxillary sinus angles when the maxillary sinus floor membrane was separated by 0 and 4 mm. The stress of the maxillary sinus floor membrane was analyzed and compared. RESULTS: When the maxillary sinus floor membrane was separated by 0 mm and elevated to 10 mm, the peak stress values of the implant on the maxillary sinus floor membrane at three different angles were as follows: maxillary sinus I: 5.14-78.32 MPa; maxillary sinus II: 2.81-73.89 MPa; and maxillary sinus III: 2.82-51.87 MPa. When the maxillary sinus floor membrane was separated by 4 mm and elevated to 10 mm, the corresponding values were as follows: maxillary sinus I: 0.50-7.25 MPa; maxillary sinus II: 0.81-16.55 MPa; and maxillary sinus III: 0.49-22.74 MPa. CONCLUSION: The risk of sinus floor membrane rupture is greatly reduced after adequate dissection of the maxillary sinus floor membrane when performing modified internal sinus elevation in a narrow maxillary sinus. In a wide maxillary sinus, the risk of rupture or perforation of the wider maxillary sinus floor is reduced, regardless of whether traditional or modified internal sinus elevation is performed at the same height.

[Association between the change in the job facilitating and inhibiting factors of care staff due to the employment of older assistant workers and the emotional exhaustion among care staff].

Objectives　The mental health condition of care staff in Japan is becoming problematic. Older assistant workers are currently being employed to assist care staff with their jobs and alleviate their job burden. This employment of older assistant workers is drawing attention; however, their influence on the job facilitating and inhibiting factors of care staff and the association with the care staff's emotional exhaustion remains unclear. In this study, we aim to examine how the employment of older care assistant workers relates to the job-facilitating and job-inhibiting factors of care staff and explore that association with the care staff's emotional exhaustion.Methods　Data from a mail survey of geriatric health services facilities with older assistant workers were analyzed. Among the answers obtained from the care staff, answers from 5,185 who reported working in facilities that employ older assistant workers (over the age of 60) were analyzed. The Emotional Exhaustion subscale of the Japanese Version of the Burnout Questionnaire was used as the dependent variable. The change in job-facilitating and job-inhibiting factors of care staff due to the employment of older assistant workers (improve, maintain/exacerbate) was explored for nine contents.Results　Care staff reported a decrease in the total volume of the task (63.6%), less stress during daily tasks (39.8%), and more concentration on the tasks that require expert care knowledge (38.0%). The results of multiple regression analysis showed that the emotional exhaustion score of care staff was low when the total volume of tasks decreased (ß=－0.383, 95%CI=－0.719, －0.047), when less stress was perceived during daily tasks (ß=－0.432, 95%CI=－0.796, －0.068), when concentration on tasks that required expert care knowledge increased (ß=－0.574, 95%CI=－0.937, －0.210), and when human relationships among staff improved (ß=－0.871, 95%CI=－1.263, －0.480). Conversely, an increase in tasks requiring work with regional personnel and organizations (ß=0.800, 95%CI=0.162, 1.437) was associated with a high emotional exhaustion score.Conclusion　The employment of older care workers was related to the job-facilitating or job-inhibiting factors of care staff, and the change in these factors was associated with lower emotional exhaustion. The employment of older personnel may lower the risk of burnout among care staff.

Novel Association of KLRC4-KLRK1 Gene Polymorphisms with Susceptibility and Progression of Antithyroid Drug-Induced Agranulocytosis.

OBJECTIVE: Antithyroid drug (ATD)-induced agranulocytosis (TIA) is the most serious adverse effect during ATD treatment of Graves' disease (GD). Previously, the MICA gene was reported to be associated with TIA. MICA protein is an important ligand for the NKG2D protein, which is encoded by the KLRK1 gene and KLRC4-KLRK1 read-through transcription. This study further investigated the association between KLRC4-KLRK1 gene polymorphisms and susceptibility to TIA. METHODS: Twenty-eight candidate single nucleotide polymorphisms (SNPs) on KLRC4-KLRK1 read-through transcription were evaluated by the iPLEX MassARRAY system in 209 GD control patients and 38 TIA cases. RESULTS: A significant association of rs2734565 polymorphism with TIA was found (p=0.02, OR=1.80, 95% CI=1.09-2.96). The haplotype C-A-A-C-G, including rs2734565-C, was associated with a significantly higher risk of TIA (p=4.79E-09, OR=8.361, 95% CI=3.737-18.707). In addition, the interval time from hyperthyroidism to agranulocytosis onset was shorter in patients carrying the rs2734565-C allele than in non-carrying groups (45.00 (14.00-6570.00) d vs. 1080.00 (30.00-3600.00) d, p=0.046), and the interval from ATD treatment to agranulocytosis onset was also shorter in patients carrying rs2734565-C allele (29.00 (13.00-75.00) d vs. 57.50 (21.00-240.00) d, p=0.023). CONCLUSIONS: The findings suggest that the KLRC4-KLRK1 gene polymorphism is associated with susceptibility and progression of ATD-induced agranulocytosis. Patients carrying the rs2734565-C allele had a higher susceptibility and faster onset time of TIA.

Expansion of Pathogenic Cardiac Macrophages in Immune Checkpoint Inhibitor Myocarditis.

BACKGROUND: Immune checkpoint inhibitors (ICIs), antibodies targeting PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1) or CTLA4 (cytotoxic T-lymphocyte-associated protein 4), have revolutionized cancer management but are associated with devastating immune-related adverse events including myocarditis. The main risk factor for ICI myocarditis is the use of combination PD-1 and CTLA4 inhibition. ICI myocarditis is often fulminant and is pathologically characterized by myocardial infiltration of T lymphocytes and macrophages. Although much has been learned about the role of T-cells in ICI myocarditis, little is understood about the identity, transcriptional diversity, and functions of infiltrating macrophages. METHODS: We used an established murine ICI myocarditis model (Ctla4+/-Pdcd1-/- mice) to explore the cardiac immune landscape using single-cell RNA-sequencing, immunostaining, flow cytometry, in situ RNA hybridization, molecular imaging, and antibody neutralization studies. RESULTS: We observed marked increases in CCR2 (C-C chemokine receptor type 2)+ monocyte-derived macrophages and CD8+ T-cells in this model. The macrophage compartment was heterogeneous and displayed marked enrichment in an inflammatory CCR2+ subpopulation highly expressing Cxcl9 (chemokine [C-X-C motif] ligand 9), Cxcl10 (chemokine [C-X-C motif] ligand 10), Gbp2b (interferon-induced guanylate-binding protein 2b), and Fcgr4 (Fc receptor, IgG, low affinity IV) that originated from CCR2+ monocytes. It is important that a similar macrophage population expressing CXCL9, CXCL10, and CD16α (human homologue of mouse FcgR4) was expanded in patients with ICI myocarditis. In silico prediction of cell-cell communication suggested interactions between T-cells and Cxcl9+Cxcl10+ macrophages via IFN-γ (interferon gamma) and CXCR3 (CXC chemokine receptor 3) signaling pathways. Depleting CD8+ T-cells or macrophages and blockade of IFN-γ signaling blunted the expansion of Cxcl9+Cxcl10+ macrophages in the heart and attenuated myocarditis, suggesting that this interaction was necessary for disease pathogenesis. CONCLUSIONS: These data demonstrate that ICI myocarditis is associated with the expansion of a specific population of IFN-γ-induced inflammatory macrophages and suggest the possibility that IFN-γ blockade may be considered as a treatment option for this devastating condition.

Directly imaging excited state-resolved transient structures of water induced by valence and inner-shell ionisation.

Real-time imaging of transient structure of the electronic excited state is fundamentally critical to understand and control ultrafast molecular dynamics. The ejection of electrons from the inner-shell and valence level can lead to the population of different excited states, which trigger manifold ultrafast relaxation processes, however, the accurate imaging of such electronic state-dependent structural evolutions is still lacking. Here, by developing the laser-induced electron recollision-assisted Coulomb explosion imaging approach and molecular dynamics simulations, snapshots of the vibrational wave-packets of the excited (A) and ground states (X) of D2O+ are captured simultaneously with sub-10 picometre and few-femtosecond precision. We visualise that θDOD and ROD are significantly increased by around 50∘ and 10 pm, respectively, within approximately 8 fs after initial ionisation for the A state, and the ROD further extends 9 pm within 2 fs along the ground state of the dication in the present condition. Moreover, the ROD can stretch more than 50 pm within 5 fs along autoionisation state of dication. The accuracies of the results are limited by the simulations. These results provide comprehensive structural information for studying the fascinating molecular dynamics of water, and pave the way towards to make a movie of excited state-resolved ultrafast molecular dynamics and light-induced chemical reaction.

Identification of the Solid Stem Suppressor Gene Su-TdDof in Synthetic Hexaploid Wheat Syn-SAU-117.

Lodging is one of the most important factors affecting the high and stable yield of wheat worldwide. Solid-stemmed wheat has higher stem strength and lodging resistance than hollow-stemmed wheat does. There are many solid-stemmed varieties, landraces, and old varieties of durum wheat. However, the transfer of solid stem genes from durum wheat is suppressed by a suppressor gene located on chromosome 3D in common wheat, and only hollow-stemmed lines have been created. However, synthetic hexaploid wheat can serve as a bridge for transferring solid stem genes from tetraploid wheat to common wheat. In this study, the F1, F2, and F2:3 generations of a cross between solid-stemmed Syn-SAU-119 and semisolid-stemmed Syn-SAU-117 were developed. A single dominant gene, which was tentatively designated Su-TdDof and suppresses stem solidity, was identified in synthetic hexaploid wheat Syn-SAU-117 by using genetic analysis. By using bulked segregant RNA-seq (BSR-seq) analysis, Su-TdDof was mapped to chromosome 7DS and flanked by markers KASP-669 and KASP-1055 within a 4.53 cM genetic interval corresponding to 3.86 Mb and 2.29 Mb physical regions in the Chinese Spring (IWGSC RefSeq v1.1) and Ae. tauschii (AL8/78 v4.0) genomes, respectively, in which three genes related to solid stem development were annotated. Su-TdDof differed from a previously reported solid stem suppressor gene based on its origin and position. Su-TdDof would provide a valuable example for research on the suppression phenomenon. The flanking markers developed in this study might be useful for screening Ae. tauschii accessions with no suppressor gene (Su-TdDof) to develop more synthetic hexaploid wheat lines for the breeding of lodging resistance in wheat and further cloning the suppressor gene Su-TdDof.

Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties.

The treatment of chronic and non-healing wounds in diabetic patients remains a major medical problem. Recent reports have shown that hydrogel wound dressings might be an effective strategy for treating diabetic wounds due to their excellent hydrophilicity, good drug-loading ability and sustained drug release properties. As a typical example, hyaluronic acid dressing (Healoderm) has been demonstrated in clinical trials to improve wound-healing efficiency and healing rates for diabetic foot ulcers. However, the drug release and degradation behavior of clinically-used hydrogel wound dressings cannot be adjusted according to the wound microenvironment. Due to the intricacy of diabetic wounds, antibiotics and other medications are frequently combined with hydrogel dressings in clinical practice, although these medications are easily hindered by the hostile environment. In this case, scientists have created responsive-hydrogel dressings based on the microenvironment features of diabetic wounds (such as high glucose and low pH) or combined with external stimuli (such as light or magnetic field) to achieve controllable drug release, gel degradation, and microenvironment improvements in order to overcome these clinical issues. These responsive-hydrogel dressings are anticipated to play a significant role in diabetic therapeutic wound dressings. Here, we review recent advances on responsive-hydrogel dressings towards diabetic wound healing, with focus on hydrogel structure design, the principle of responsiveness, and the behavior of degradation. Last but not least, the advantages and limitations of these responsive-hydrogels in clinical applications will also be discussed. We hope that this review will contribute to furthering progress on hydrogels as an improved dressing for diabetic wound healing and practical clinical application.

A polystyrene-based ESIPT fluorescent polymeric probe for highly sensitive detection of chromium(vi) ions and protein staining.

A "two-step" preparation method of an excited-state intermolecular proton transfer (ESIPT) fluorescent polymer (f-PP) is reported here. The synthesis of f-PP involves the acetylation of polystyrene and a "multicomponent one pot" reaction. The as-prepared polymer bears a group of ESIPT fluorescent units, enabling it to exhibit high brightness, moderate solubility and ESIPT fluorescence. F-PP gives off tautomeric bright green fluorescence under UV-tamp and the dual-emission could be specifically suppressed by Cr(vi). This phenomenon cannot be elicited by other competing species. On this basis, an ESIPT polymeric probe-based method for the determination of Cr(vi) was developed, offering high sensitivity (19.5 nM) and selectivity. The f-PP was successfully used to detect Cr(vi) in real water samples by standard adding methods, indicating its application feasibility.

Defining cardiac functional recovery in end-stage heart failure at single-cell resolution.

Recovery of cardiac function is the holy grail of heart failure therapy yet is infrequently observed and remains poorly understood. In this study, we performed single-nucleus RNA sequencing from patients with heart failure who recovered left ventricular systolic function after left ventricular assist device implantation, patients who did not recover and non-diseased donors. We identified cell-specific transcriptional signatures of recovery, most prominently in macrophages and fibroblasts. Within these cell types, inflammatory signatures were negative predictors of recovery, and downregulation of RUNX1 was associated with recovery. In silico perturbation of RUNX1 in macrophages and fibroblasts recapitulated the transcriptional state of recovery. Cardiac recovery mediated by BET inhibition in mice led to decreased macrophage and fibroblast Runx1 expression and diminished chromatin accessibility within a Runx1 intronic peak and acquisition of human recovery signatures. These findings suggest that cardiac recovery is a unique biological state and identify RUNX1 as a possible therapeutic target to facilitate cardiac recovery.

A fluorescent probe based on modulation of ESIPT signaling for the highly selective detection of N2H4 and cell-imaging.

The broad occurrence of the hydrazine (N2H4) residues in aqueousenvironment is a potential threat to human health. Currently, the mainstream strategy for designing N2H4-specific probes is to functionalize a fluorophore with nucleophilic sites for the reductionreaction with N2H4. In this work, we designed and synthesized an excited-state intermolecular proton transfer (inter-ESPT) fluorescent dye(2-amino-4-(4-methoxyphenyl)-7,8-dihydro-5H-spiro[quinoline-6,2'-[1,3]dioxolane]-3-carbonitrilem, DQN) and used it as a probe to sense N2H4. DQN exhibits blue fluorescence in conventional solvents, which is assigned to its normal emission. In the presence of N2H4, the probe DQN can anchor the N2H4 molecule via hydrogen binding, enabling DQN to undergo inter-ESPT process and light up its tautomeric fluorescence. From this basis, an inter-ESPT-based method for N2H4 detection was established, offering high selectivity and sensitivity (11.5 nM). Furthermore, we demonstrated that the probe DQN can recognize the proteins in living cells, affording cell-imaging. This research provides a promising sensing strategy for monitoring N2H4 in water environments and this inter-ESPT dye is a powerful tool for cell-imaging.