DNA methylation analysis reveals local changes in resistant and susceptible soybean lines in response to Phytophthora sansomeana.

Phytophthora sansomeana is an emerging oomycete pathogen causing root rot in many agricultural species including soybean. However, as of now, only one potential resistance gene has been identified in soybean, and our understanding of how genetic and epigenetic regulation in soybean contributes to responses against this pathogen remains largely unknown. In this study, we performed whole genome bisulfite sequencing (WGBS) on two soybean lines, Colfax (resistant) and Williams 82 (susceptible) in response to P. sansomeana at two time points: 4 and 16 hours post inoculation to compare their methylation changes. Our findings revealed that there were no significant changes in genome-wide CG, CHG (H = A, T, or C), and CHH methylation. However, we observed local methylation changes, specially an increase in CHH methylation around genes and transposable elements (TEs) after inoculation, which occurred earlier in the susceptible line and later in the resistant line. After inoculation, we identified differentially methylated regions (DMRs) in both Colfax and Williams 82, with a predominant presence in TEs. Notably, our data also indicated that more TEs exhibited changes in their methylomes in the susceptible line compared to the resistant line. Furthermore, we discovered 837 DMRs within or flanking 772 differentially expressed genes (DEGs) in Colfax and 166 DMRs within or flanking 138 DEGs in Williams 82. These DEGs had diverse functions, with Colfax primarily showing involvement in metabolic process, defense response, plant and pathogen interaction, anion and nucleotide binding, and catalytic activity, while Williams 82 exhibited a significant association with photosynthesis. These findings suggest distinct molecular responses to P. sansomeana infection in the resistant and susceptible soybean lines.

Association of metabolic syndrome severity with frailty progression among Chinese middle and old-aged adults: a longitudinal study.

BACKGROUND: The binary diagnosis of Metabolic Syndrome(MetS) fails to accurately evaluate its severity, and the association between MetS severity and frailty progression remains inadequately elucidated. This study aims to clarify the relationship between the severity of MetS and the progression of frailty among the middle-aged and elderly population in China. METHOD: Participants from the 2011-2018 China Health and Retirement Longitudinal Study(CHARLS) were included for a longitudinal analysis. The study employs a frailty index(FI) based on 32 health deficits to diagnose frailty and to assess FI trajectories. An age-sex-ethnicity-specific MetS scoring model (MetS score) was used to assess metabolic syndrome severity in Chinese adults. The Cumulative MetS score from 2012 to 2015 was calculated using the formula: (MetS score in wave 1 + MetS score in wave 3) / 2 × time(2015 - 2012). The association between MetS score, Cumulative MetS score, and the risk and trajectory of frailty were evaluated using Cox regression/logistic regression, and linear mixed models. Restricted Cubic Splines(RCS) models were utilized to detect potential non-linear associations. RESULTS: A higher MetS score was significantly associated with an increased risk of frailty(HR per 1 SD increase = 1.205; 95%CI: 1.14 to 1.273) and an accelerated FI trajectory(ß per 1 SD increase = 0.113 per year; 95%CI: 0.075 to 0.15 per year). Evaluating changes in MetS score using a Cumulative MetS score indicated that each 1 SD increase in the Cumulative MetS score increased the risk of frailty by 22.2%(OR = 1.222; 95%CI: 1.133 to 1.319) and accelerated the rate of increase in FI(ß = 0.098 per year; 95%CI: 0.058 to 0.138 per year). RCS model results demonstrated a dose-response curve relationship between MetS score and Cumulative MetS score with frailty risk. Stratified analysis showed consistency across subgroups. The interaction results indicate that in males and individuals under aged 60, MetS score may accelerate the increase in FI, a finding consistent across both models. CONCLUSIONS: Our findings underscore the positive correlation between the severity of MetS and frailty progression in the middle-aged and elderly, highlighting the urgent need for early identification of MetS and targeted interventions to reduce the risk of frailty.

The Value of Neutrophil-to-Lymphocyte Ratio in Predicting Mortality After Transjugular Intrahepatic Portosystemic Shunt Placement.

Background and Aims: The objective of this study was to investigate the effect of neutrophil-to-lymphocyte ratio (NLR) on the survival of cirrhotic patients with esophagogastric variceal bleeding (EGVB) treated with transjugular intrahepatic portosystemic shunt (TIPS). Methods: A total of 293 patients treated with TIPS were included. The receiver operator characteristic curve (ROC) was used to calculate the optimal cut-off values of parameters such as NLR. The Kaplan-Meier curve and Cox proportional risk model were used to evaluate the effects of NLR and other variables on 2-year all-cause mortality. Results: The area under the ROC for NLR was 0.634, with an optimal cutoff value of 4.9. Two-year mortality rates for patients with high (≥4.9) and low (<4.9) NLR were 22.1% and 9.3%, respectively (Log rank test: P = 0.002). After correcting for confounders, multivariate analysis demonstrated that NLR ≥ 4.9 (HR = 2.741, 95% CI 1.467-5.121, P = 0.002), age ≥ 63 (HR = 3.403, 95% CI 1.835-6.310, P < 0.001), and gender (male) (HR = 2.842, 95% CI 1.366-5.912, P = 0.001) were independent risk factors for the mortality outcome. Considering the stratification of early and selective TIPS treatment, high NLR still significantly increased the risk of mortality for patients (Log rank test: P = 0.007, HR = 2.317, 95% CI 1.232-4.356). Conclusion: NLR can help to predict survival in EGVB patients after TIPS, and the type of TIPS should also be considered in practical applications.

Local delivery of carboplatin-loaded hydrogel and calcium carbonate enables two-stage drug release for limited-dose radiation to eliminate mouse malignant glioma.

Postoperative radiotherapy remains the gold standard for malignant glioma treatment. Clinical limitations, including tumor growth between surgery and radiotherapy and the emergence of radioresistance, reduce treatment effectiveness and result in local disease progression. This study aimed to develop a local drug delivery system to inhibit tumor growth before radiotherapy and enhance the subsequent anticancer effects of limited-dose radiotherapy. We developed a compound of carboplatin-loaded hydrogel (CPH) incorporated with carboplatin-loaded calcium carbonate (CPCC) to enable two-stage (peritumoral and intracellular) release of carboplatin to initially inhibit tumor growth and to synergize with limited-dose radiation (10 Gy in a single fraction) to eliminate malignant glioma (ALTS1C1 cells) in a C57BL/6 mouse subcutaneous tumor model. The doses of carboplatin in CPH and CPCC treatments were 150 µL (carboplatin concentration of 5 mg/mL) and 15 mg (carboplatin concentration of 4.1 µg/mg), respectively. Mice receiving the combination of CPH-CPCC treatment and limited-dose radiation exhibited significantly reduced tumor growth volume compared to those receiving double-dose radiation alone. Furthermore, combining CPH-CPCC treatment with limited-dose radiation resulted in significantly longer progression-free survival than combining CPH treatment with limited-dose radiation. Local CPH-CPCC delivery synergized effectively with limited-dose radiation to eliminate mouse glioma, offering a promising solution for overcoming clinical limitations.

Enhanced non-viral gene delivery via calcium phosphate/DNA co-precipitates with low-voltage pulse electroporation in NK-92 cells for immunocellular therapy.

Achieving high cell transfection efficiency is essential for various cell types in numerous disease applications. However, the efficient introduction of genes into natural killer (NK) cells remains a challenge. In this study, we proposed a design strategy for delivering exogenous genes into the NK cell line, NK-92, using a modified non-viral gene transfection method. Calcium phosphate/DNA nanoparticles (pDNA-CaP NPs) were prepared using co-precipitation methods and combined with low-voltage pulse electroporation to facilitate NK-92 transfection. The results demonstrated that the developed pDNA-CaP NPs exhibited a uniform diameter of approximately 393.9 nm, a DNA entrapment efficiency of 65.8%, and a loading capacity of 15.9%. Furthermore, at three days post-transfection, both the transfection efficiency and cell viability of NK-92 were significantly improved compared to standalone plasmid DNA (pDNA) electroporation or solely relying on the endocytosis pathway of pDNA-CaP NPs. This study provides valuable insights into a novel approach that combines calcium phosphate nanoparticles with low-voltage electroporation for gene delivery into NK-92 cells, offering potential advancements in cell therapy.

Serum Fructosamine as an Indicator of Perioperative Complications in Patients Undergoing Foot and Ankle Surgery.

Background: Patients with poor glycemic control are at increased risk of postoperative complications. Hemoglobin A1c (HbA1c) has traditionally been used to assess preoperative glycemic control, but with limitations. More recently, fructosamine has been tested preoperatively in patients undergoing elective total joint arthroplasty. This study aims to assess whether preoperative serum fructosamine can be used to avoid adverse outcomes in patients undergoing foot and ankle surgery. Methods: This was a retrospective chart review of all patients who underwent foot and ankle surgeries at 2 level 1 trauma centers from January 2020 to December 2021. Of those, 305 patients were tested for HbA1c and fructosamine levels preoperatively. Adverse outcomes were assessed over 30 and 90 days. Outcomes of interest were surgical site infection, wound dehiscence, unplanned return to the operating room, unplanned readmission, and death. Data were analyzed using independent 2-sample t tests. A mixed effects model was used for multivariate analysis. P values less than .05 were considered statistically significant. Results: Preoperative serum fructosamine was significantly higher (P = .029) in those with complications within 90 days compared to those without. The mean preoperative fructosamine level was 269.2 µmol/L (SD = 58.85) in those who did have a complication vs 247.2 µmol/L (SD = 53.95) in those who did not. Clinically significant fructosamine threshold was determined using 2 different methods. Fructosamine was found to be non-inferior to HbA1c in accurately predicting postoperative complications. Conclusion: Fructosamine is a serum marker that reflects nearer term glycemic control than HbA1c. Elevation in preoperative fructosamine is associated with increased perioperative complications after foot and ankle surgery within 90 days. Preoperative fructosamine may be used in patient optimization and risk stratification when determining candidacy and timing for elective foot and ankle surgeries. Level of evidence: Level III, retrospective cohort study.

Expression of CD6 in Aggressive NK/T-cell Neoplasms and Assessment as a Potential Therapeutic Target: A Bone Marrow Pathology Group Study.

BACKGROUND: Aggressive NK/T-Cell neoplasms are rare hematological malignancies characterized by the abnormal proliferation of NK or NK-like T (NK/T) cells. CD6 is a transmembrane signal transducing receptor involved in lymphocyte activation and differentiation. This study aimed to investigate the CD6 expression in these malignancies and explore the potential of targeting CD6 in these diseases. MATERIALS AND METHODS: We conducted a retrospective study with totally 41 cases to investigate the expression of CD6 by immunohistochemistry, including aggressive NK-cell leukemia/lymphoma (ANKLL: N = 10) and extranodal NK/T-cell lymphoma (ENKTL: N = 31). A novel ANKLL model was applied for proof-of-concept functional studies of a CD6 antibody-drug-conjugate (CD6-ADC) both in vitro and in animal trial. RESULTS: CD6 was expressed in 68.3% (28/41) of cases (70% (7/10) of ANKLL and 67.7% (21/31) of ENKTL). The median overall survival (OS) for ANKLL and ENTKL cases was 1 and 12 months, respectively, with no significant difference in OS based on CD6 expression (p > 0.05, Kaplan-Meier with log-rank test). In vitro exposure of the CCANKL cell line, derived from an ANKL patient, to an anti-CD6ADC resulted in dose dependent induction of apoptosis. Furthermore, CCANKL engraftment in NSG mice could be blocked by treatment with the anti-CD6 ADC. CONCLUSION: To date, this is the first report to explore the expression of CD6 in ANKLL and ENKTL and confirms its expression in the majority of cases. The in vitro and in vivo data support further investigation of CD6 as a potential therapeutic target in these aggressive NK/T-cell malignancies.

The addition of nimotuzumab during concurrent chemoradiotherapy improved survival outcomes in locally advanced nasopharyngeal carcinoma patients with optimal response to induction chemotherapy.

OBJECTIVE: To investigate the impact of response to induction chemotherapy (IC) on survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LANPC) and evaluate the efficacy of adding nimotuzumab to concurrent chemoradiotherapy (CCRT) based on different responses to IC. METHODS: We retrospectively included patients with stage III-IVA NPC who underwent IC with and without nimotuzumab during CCRT. Statistical analysis included the chi-square test, propensity score matching, Kaplan-Meier survival analysis, and Cox proportional hazards model. RESULTS: Among 383 identified patients, 216 (56.4%) received nimotuzumab during CCRT, while 167 (43.6%) did not. Following IC, 269 (70.2%) patients showed a complete response (CR) or partial response (PR), and 114 (29.8%) had stable disease (SD) or progressive disease (PD). The response to IC independently influenced disease-free survival (DFS) and overall survival (OS). Patients achieving CR/PR demonstrated significantly higher 3-year DFS (80.3% vs. 70.6%, P = 0.031) and OS (90.9% vs. 83.2%, P = 0.038) than those with SD/PD. The addition of nimotuzumab during CCRT significantly improved DFS (P = 0.006) and OS (P = 0.037) for CR/PR patients but not for those with SD/PD. CONCLUSIONS: This study emphasizes the importance of IC response in LANPC and highlights the potential benefits of nimotuzumab during CCRT for improving survival outcomes in CR/PR patients. Tailored treatment approaches for SD/PD patients warrant further investigation.

Hepatic arterial infusion of GEMOX plus systemic gemcitabine chemotherapy combined with lenvatinib and PD-1 inhibitor in large unresectable intrahepatic cholangiocarcinoma.

PURPOSE: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) in combination with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with large unresectable intrahepatic cholangiocarcinoma (uICC). METHODS: From November 2019 to December 2022, 21 large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor were retrospectively enrolled. Local tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AEs were evaluated by the common terminology criteria for adverse events (CTCAE) version 5.0. RESULTS: After a median follow-up duration of 16.0 months (range 5-43.5 months), 17 patients had died. The median OS was 19.5 months (range 9-43.5 months), and the median PFS was 6.0 months (range 2.5-38.5 months). The 1-, 2-, and 3-year OS rates were 71.4 %, 42.9 %, and 19.0 %, respectively. The 1-, 2-, and 3-year PFS rates were 33.3 %, 19.0 %, and 9.5 %, respectively. Complete response, partial response, stable disease, and progressive disease were observed in 0 (0 %), 11 (52.3 %), 5 (23.8 %), and 5 (23.8 %) patients, respectively. The disease control rate and objective response rate were 76.1 % and 52.3 %, respectively. None of the enrolled patients experienced grade 5 AEs. CONCLUSIONS: GEMOX-HAIC plus GEM-SYS in combination with lenvatinib and PD-1 inhibitor was effective and well tolerated for patients with large uICC.

Influence of static cartoons combined with dynamic virtual environments on preoperative anxiety of preschool-aged children undergoing surgery.

BACKGROUND: Preschoolers become anxious when they are about to undergo anesthesia and surgery, warranting the development of more appropriate and effective interventions. AIM: To explore the effect of static cartoons combined with dynamic virtual environments on preoperative anxiety and anesthesia induction compliance in preschool-aged children undergoing surgery. METHODS: One hundred and sixteen preschool-aged children were selected and assigned to the drug (n = 37), intervention (n = 40), and control (n = 39) groups. All the children received routine preoperative checkups and nursing before being transferred to the preoperative preparation room on the day of the operation. The drug group received 0.5 mg/kg midazolam and the intervention group treatment consisting of static cartoons combined with dynamic virtual environments. The control group received no intervention. The modified Yale Preoperative Anxiety Scale was used to evaluate the children's anxiety level on the day before surgery (T0), before leaving the preoperative preparation room (T1), when entering the operating room (T2), and at anesthesia induction (T3). Compliance during anesthesia induction (T3) was evaluated using the Induction Compliance Checklist (ICC). Changes in mean arterial pressure (MAP), heart rate (HR), and respiratory rate (RR) were also recorded at each time point. RESULTS: The anxiety scores of the three groups increased variously at T1 and T2. At T3, both the drug and intervention groups had similar anxiety scores, both of which were lower than those in the control group. At T1 and T2, MAP, HR, and RR of the three groups increased. The drug and control groups had significantly higher MAP and RR than the intervention group at T2. At T3, the MAP, HR, and RR of the drug group decreased and were significantly lower than those in the control group but were comparable to those in the intervention group. Both the drug and intervention groups had similar ICC scores and duration of anesthesia induction (T3), both of which were higher than those of the control group. CONCLUSION: Combining static cartoons with dynamic virtual environments as effective as medication, specifically midazolam, in reducing preoperative anxiety and fear in preschool-aged children. This approach also improve their compliance during anesthesia induction and helped maintain their stable vital signs.

CD6 Regulates CD4 T Follicular Helper Cell Differentiation and Humoral Immunity During Murine Coronavirus Infection.

During activation the T cell transmembrane receptor CD6 becomes incorporated into the T cell immunological synapse where it can exert both co-stimulatory and co-inhibitory functions. Given the ability of CD6 to carry out opposing functions, this study sought to determine how CD6 regulates early T cell activation in response to viral infection. Infection of CD6 deficient mice with a neurotropic murine coronavirus resulted in greater activation and expansion of CD4 T cells in the draining lymph nodes. Further analysis demonstrated that there was also preferential differentiation of CD4 T cells into T follicular helper cells, resulting in accelerated germinal center responses and emergence of high affinity virus specific antibodies. Given that CD6 conversely supports CD4 T cell activation in many autoimmune models, we probed potential mechanisms of CD6 mediated suppression of CD4 T cell activation during viral infection. Analysis of CD6 binding proteins revealed that infection induced upregulation of Ubash3a, a negative regulator of T cell receptor signaling, was hindered in CD6 deficient lymph nodes. Consistent with greater T cell activation and reduced UBASH3a activity, the T cell receptor signal strength was intensified in CD6 deficient CD4 T cells. These results reveal a novel immunoregulatory role for CD6 in limiting CD4 T cell activation and deterring CD4 T follicular helper cell differentiation, thereby attenuating antiviral humoral immunity.

Identification of Multievent Stochastic Fuzzy Discrete Event Systems.

We recently introduced a novel category of fuzzy discrete event systems (FDESs) termed stochastic FDESs (SFDESs), wherein multiple fuzzy automata occur randomly with different probabilities. We also developed two techniques for identifying event transition matrices in single-event SFDES employing the max-product fuzzy inference. One of them, named the equation-systems-based technique, focuses on the single-event SFDES identification, where the fuzzy automaton of each FDES has only one event. Expanding on our research, this article delves into multievent SFDES identification, allowing each FDES to encompass a sequence of events. This is a new research direction that has not been mentioned in the literature before. Upon activation of an FDES, all its events occur sequentially. Our mathematical proof first establishes the associativity of the max-product inference operation, leading to the introduction of a pivotal and novel concept called an equivalent overall event transition matrix for a consecutive event sequence. This concept establishes a theoretical framework for utilizing the equation-systems-based technique in a novel three-step method for identifying multievent SFDESs. The technique is employed in the first two steps to: 1) determine the number of fuzzy automata in an SFDES and 2) calculate their occurrence frequencies. In the third step, multievent transition matrices of the SFDES are learned by using the stochastic-gradient-descent-based algorithms that we previously developed for multievent FDESs, provided the numbers of consecutive events for each fuzzy automaton within the SFDES are known. Theoretical analysis reveals, for the first time, the interconnections between the event transition matrices learned by the algorithms, the equivalent overall event transition matrices derived from these matrices, and the target event transition matrices. To illustrate our findings, we present an informative example.

Association between dichotomized VASARI feature and overall survival in glioblastoma patients: a single-institution propensity score matching analysis.

OBJECTIVES: This study aimed to investigate the intra- and inter-observer consistency of the Visually Accessible Rembrandt Images (VASARI) feature set before and after dichotomization, and the association between dichotomous VASARI features and the overall survival (OS) in glioblastoma (GBM) patients. METHODS: This retrospective study included 351 patients with pathologically confirmed IDH1 wild-type GBM between January 2016 and June 2022. Firstly, VASARI features were assessed by four radiologists with varying levels of experience before and after dichotomization. Cohen's kappa coefficient (κ) was calculated to measure the intra- and inter-observer consistency. Then, after adjustment for confounders using propensity score matching, Kaplan-Meier curves were used to compare OS differences for each dichotomous VASARI feature. Next, patients were randomly stratified into a training set (n = 211) and a test set (n = 140) in a 3:2 ratio. Based on the training set, Cox proportional hazards regression analysis was adopted to develop combined and clinical models to predict OS, and the performance of the models was evaluated with the test set. RESULTS: Eleven VASARI features with κ value of 0.61-0.8 demonstrated almost perfect agreement after dichotomization, with the range of κ values across all readers being 0.874-1.000. Seven VASARI features were correlated with GBM patient OS. For OS prediction, the combined model outperformed the clinical model in both training set (C-index, 0.762 vs. 0.723) and test set (C-index, 0.812 vs. 0.702). CONCLUSION: The dichotomous VASARI features exhibited excellent inter- and intra-observer consistency. The combined model outperformed the clinical model for OS prediction.

Unusual plastic strain-induced phase transformation phenomena in silicon.

Pressure-induced phase transformations (PTs) in Si, the most important electronic material, have been broadly studied, whereas strain-induced PTs have never been studied in situ. Here, we reveal in situ various important plastic strain-induced PT phenomena. A correlation between the direct and inverse Hall-Petch effect of particle size on yield strength and pressure for strain-induced PT is predicted theoretically and confirmed experimentally for Si-I→Si-II PT. For 100 nm particles, the strain-induced PT Si-I→Si-II initiates at 0.3 GPa under both compression and shear while it starts at 16.2 GPa under hydrostatic conditions. The Si-I→Si-III PT starts at 0.6 GPa but does not occur under hydrostatic pressure. Pressure in small Si-II and Si-III regions of micron and 100 nm particles is ∼5-7 GPa higher than in Si-I. For 100 nm Si, a sequence of Si-I → I + II → I + II + III PT is observed, and the coexistence of four phases, Si-I, II, III, and XI, is found under torsion. Retaining Si-II and single-phase Si-III at ambient pressure and obtaining reverse Si-II→Si-I PT demonstrates the possibilities of manipulating different synthetic paths. The obtained results corroborate the elaborated dislocation pileup-based mechanism and have numerous applications for developing economic defect-induced synthesis of nanostructured materials, surface treatment (polishing, turning, etc.), and friction.

Vision-based estimation of fatigue and engagement in cognitive training sessions.

Computerized cognitive training (CCT) is a scalable, well-tolerated intervention that has promise for slowing cognitive decline. The effectiveness of CCT is often affected by a lack of effective engagement. Mental fatigue is a the primary factor for compromising effective engagement in CCT, particularly in older adults at risk for dementia. There is a need for scalable, automated measures that can constantly monitor and reliably detect mental fatigue during CCT. Here, we develop and validate a novel Recurrent Video Transformer (RVT) method for monitoring real-time mental fatigue in older adults with mild cognitive impairment using their video-recorded facial gestures during CCT. The RVT model achieved the highest balanced accuracy (79.58%) and precision (0.82) compared to the prior models for binary and multi-class classification of mental fatigue. We also validated our model by significantly relating to reaction time across CCT tasks (Waldχ2=5.16,p=0.023). By leveraging dynamic temporal information, the RVT model demonstrates the potential to accurately measure real-time mental fatigue, laying the foundation for future CCT research aiming to enhance effective engagement by timely prevention of mental fatigue.

Theoretical Study on Optoelectronic Properties of 1,4-Dithiazole-5,10-dihydrophenazine and Its B ← N-Fused Derivatives.

Recently, Liu et al. reported 1,4-dithiazole-5,10-dihydrophenazine (DTDHP) and its B ← N-fused derivative (DTHDHP-BF2), which were expected to show excellent optoelectronic properties (Angew. Chem. Int. Ed. 2022, 61, e202205893). However, their charge-transport performance and luminescence emission mechanisms have not been revealed. In this work, we used density functional theory (DFT) calculations to investigate the optoelectronic properties of DTDHP and DTHDHP-BF2 and analyzed the influence of the introduction of -BF2 on the basic parameters governing charge transport and injection in detail. Our calculation results showed that adding -BF2 could stabilize the frontier molecular orbitals and decrease the reorganization energies associated with electron transport due to the formation of B ← N bonds, and the intermolecular electronic couplings are greatly enhanced owing to the strong intermolecular F···H interactions. Based on the master equation coupled with the Marcus-Hush electron transfer theory, we theoretically predicted the charge transport properties of DTDHP and DTHDHP-BF2. The optimum hole mobility (3.87 cm2 V-1 S-1) and electron mobility (1.52 cm2 V-1 S-1) of DTHDHP-BF2 are, respectively, 3 and 9 times as high as the corresponding optimum values of compound DTDHP. Moreover, the assignments of multiple fluorescence bands in the experiment were confirmed by time-dependent density functional theory (TDDFT) calculations. The simulated emission spectra indicate that the experimental fluorescence maxima at 687 nm originates from the S1 → S0 transition of the double proton transfer phototautomer (T2H) of DTDHP, and the shoulder peak at ∼660 nm may be related to the excited-state single-proton transfer phototautomer (T1H); for DTHDHP-BF2, the experimental fluorescence maxima at 687 nm should be attributed to normal Stokes shifted emission, and the shifted fluorescence with a peak at 751 nm originates from the emission of the photodissociation product of DTHDHP-BF2.

Laminarin-modulated osmium nanozymes with high substrate-affinity and selective peroxidase-like behavior engineered colorimetric assay for hydroxyl radical scavenging capacity estimation.

Hydroxyl radical (·OH) scavenging capacity (HOSC) estimation is essential for evaluating antioxidants, natural extracts, or drugs against clinical diseases. While nanozymes offer advantages in related applications, they still face limitations in activity and selectivity. In response, this work showcases the fabrication of laminarin-modulated osmium (laminarin-Os) nanoclusters (1.45 ± 0.05 nm), functioning as peroxidase-like nanozymes within a colorimetric assay tailored for rational HOSC estimation. This study validates both the characterization and remarkable stability of laminarin-Os. By leveraging the abundant surface negative charges of laminarin-Os and the surface hydroxyls of laminarin, oxidation reactions are facilitated, augmenting laminarin-Os's affinity for 3,3',5,5'-tetramethylbenzidine (TMB) (KM = 0.04 mM). This enables the laminarin-Os-based colorimetric assay to respond to ·OH more effectively than citrate-, albumin-, or other polysaccharides-based Os. In addition, experimental results also validate the selective peroxidase-like behavior of laminarin-Os under acidic conditions. Antioxidants like ascorbic acid, glutathione, tannic acid, and cysteine inhibit absorbance at 652 nm in the colorimetric platform using laminarin-Os's peroxidase-like activity. Compared with commercial kits, this assay demonstrates superior sensitivity (e.g., responds to ascorbic acid 0.01-0.075 mM, glutathione 1-15 µg/mL, tannic acid 0.5-5 µM, and monoammonium glycyrrhizinate cysteine 1.06-10.63 µM) and HOSC testing for glutathione, tannic acid, and monoammonium glycyrrhizinate cysteine. Overall, this study introduces a novel Os nanozyme with exceptional TMB affinity and ·OH selectivity, paving the way for HOSC estimation in biomedical research, pharmaceutical analysis, drug quality control, and beyond.

Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1ß pathway.

BACKGROUND: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored. PURPOSE: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL. METHODS: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments. RESULTS: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1ß pathway and increased proinflammatory IL1ß in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1ß pathway. CONCLUSIONS: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1ß pathway, specifically by targeting AKK and tryptophan metabolites.

Identification of QTLs associated with yield-related traits and superior genotype prediction using recombinant inbred line population in tobacco.

Tobacco is an economically significant industrial crop and model plant for genetic research, yet little is known about its genetic architecture. Quantitative trait loci (QTL) analysis was performed for six agronomic traits on an F_7 population of 341 genotypes, parents, and F1 plants using 1974 SSR markers across two environments. 31 QTLs contributing single-locus additive effects on 13 linkage groups (LGs) and 6 QTL pairs contributing epistatic effects on 6 LGs, were detected by the QTLNetwork 2.0 which was developed for the mixed-linear-model-based composite interval mapping (MCIM). Notably, 5 QTLs and 1 epistatic QTL pair were found to have pleiotropic effects on some genetically related traits. Moreover, the Broad sense heritability of the detected QTLs ranged from 1.05% to 43.33%, while genotype-by-environment interaction heritability spanned from 27.09% to 56.25%. Based on the results of QTL mapping, the potential superior lines for all or specific environments were designed and evaluated. Five major QTLs were finely dissected based on the tobacco reference genome of K326, and 31 candidate genes were predicted. This study offered new insights into the complicated genetic architecture and QTL resources for efficient breeding design for genetic improvement of agronomic traits in tobacco.

A two-year prospective study to compare the peri-implant parameters of posterior implant-supported single crowns with and without mesial proximal contact loss.

Background/purpose: Interproximal contact loss may lead to food impaction and result in subsequently periodontal complications. The purpose of this prospective study was to investigate the peri-implant parameters of posterior implant-supported single crowns (SCs) with and without mesial proximal contact loss after 2 years of follow-up. Material and methods: Twenty-six patients with a total of 40 posterior implant-supported SCs with mesial adjacent natural teeth were observed for 24 months after crown insertion. The mesial proximal contacts were assessed by dental floss, then were classified as tight, weak, and open contacts. The following peri-implant parameters were evaluated, including modified plaque index (MPI), modified gingival index (MGI), and probing depth (PD) were conducted at six sites per tooth (mesiofacail, midfacial, distofacial, mesiolingual, mid-lingual and distolingual) in the 6-, 12-, 18- and 24-month following visits. Furthermore, radiographs were taken regularly in 12- and 24-month recall sections for measuring the marginal bone loss (MBL). Results: At 12-month observation, the incidence rates of weak and open contacts were 22.5 % and 12.5 %; whereas after 24 months of clinical service, the rates came up with 12.9 % and 25.6 %, respectively. No significant differences were found between the tight, weak, and open contact groups in the parameters of MPI, MGI, or PD (P > 0.05) at 12- and 24-month follow-up. None of the mean differences of the peri-implant parameters: MPI, MGI, PD and MBL had significant differences between the tight, weak, and open contact groups after 1 and 2 years of clinical service (P > 0.05). Conclusion: The presence of open, weak, and tight mesial proximal contacts had no significant effects on the peri-implant tissue conditions.