The Anti-Hypoxic Mechanism of Sesamoside Determined Using Network Pharmacology.

This study aims to elucidate the anti-hypoxia mechanism of sesamoside, an active component of Phlomis younghusbandii Mukerjee, through a network pharmacology approach. Sesamoside has demonstrated potential anti-oxidant and antiglycation activities. The hypoxia-related disease targets were collected from databases like GeneCards and OMIM. Protein-protein interaction (PPI) networks were constructed using the STRING database. GO/KEGG enrichment analysis was performed using the Metascape database to identify biological processes and signaling pathways. Our results indicate that sesamoside interacts with multiple targets related to glucose and lipid metabolism, nucleotide metabolism, and inflammatory, and we find that AKR1B1 (AR) plays a crucial role in sesamoside responses to hypoxia. Molecular docking studies were performed using Autodock software, revealing good binding activity between sesamoside and AR. We then use CCK-8 assay, qPCR, WB, and ELISA analysis to validate the role of sesamoside in regulating AR and participating in anti-hypoxia through cell experiments. The results show that compared with the hypoxia group, sesamoside treatment significantly improves the expression of AR and inflammation cytokines. In summary, this study sheds light on the anti-hypoxia mechanism of sesamoside using a network pharmacology approach, providing a theoretical basis and experimental foundation for its application in the prevention and treatment of hypoxic diseases.

Blood Pressure Trajectories During Young Adulthood and Cardiovascular Events in Later Life.

BACKGROUND: Studying the association between blood pressure (BP) trajectories during young adulthood and subsequent cardiovascular disease (CVD) risk can provide insights into how long-term BP patterns in early life influence the development of CVD later in life. METHODS: We pooled data from two US cohorts (CARDIA, FHS). We used latent growth curve models to identify distinct BP trajectory groups during ages 18-39 years. We then used Cox proportional hazards models to assess the associations between BP trajectories and CVD events (composite of coronary heart disease [CHD], stroke, and heart failure [HF]) after age 40 years. RESULTS: We included 6,579 participants and identified four distinct systolic BP trajectory groups during young adulthood. During a median follow-up of 18.2 years after age 40 years, 213 CHD, 139 stroke, 120 HF, and 400 composite CVD events occurred. Individuals in an elevated-increasing vs. low-stable systolic BP trajectory during young adulthood was associated with a higher risk of CVD after adjusting for traditional CVD risk factors, with hazard ratios (95% CI) of 3.25 (1.63, 6.46) for CHD, 3.92 (1.63, 9.43) for stroke, 8.30 (2.97, 23.17) for HF, and 3.91 (2.38, 6.41) for composite CVD outcomes. Adding BP trajectory to BP at baseline improved model discrimination for all outcomes (changes in Harrell's C-index 0.0084 to 0.0192). CONCLUSIONS: An elevated-increasing BP trajectory during young adulthood is associated with a higher risk of CVD later in life, highlighting the importance of maintaining a low-stable BP trajectory throughout the young adulthood period for prevention of CVD in later life.

Molecular Simulation Analysis of Polyurethane Molecular Structure under External Electric Field.

Polyurethane (PU) materials are extensively utilized in power equipment. This paper introduces a comprehensive evaluation method that combines electromagnetics and computational chemistry based on the Density Functional Theory (DFT) to elucidate the impact of external electric fields on the molecular structure of PU during electrical contact. The study focuses on the microstructural and molecular energy changes in the hard (HS) and soft (SS) segments of PU under the influence of an electric field of uniform intensity. Findings indicate that the total energy of HS molecules decreases markedly as the electric field intensity increases, accompanied by a significant rise in both the dipole moment and polarizability. Conversely, the total energy and polarizability of the SS molecules decrease, while the dipole moment experiences a slight increase. Under the influence of a strong electric field, HS molecules tend to stretch towards the extremities of the main chain, leading to structural instability and the cleavage of hydroxyl O-H bonds. Meanwhile, the carbon chain of the SS molecules twists towards the center under the electric field, with no chemical bond rupture observed. At an electric field intensity of 8.227 V/nm, the HOMO-LUMO gap of the HS molecule narrows sharply, signifying a rapid decline in the molecular structure stability, corroborated by infrared spectroscopy analysis. These findings offer theoretical insights and guidance for the modification of PU materials in power equipment applications.

Harnessing the CD44-targeted delivery of self-assembled hyaluronan nanogel to reverse the antagonism between Cisplatin and Gefitinib in NSCLC cancer therapy.

The combination of the standard platinum-based chemotherapy with EGFR-tyrosine kinase inhibitor Gefitinib (Gef) principally boosts the anticancer efficacy of advanced non-small cell lung cancer (NSCLC) through non-overlapping mechanisms of action, however the clinical trials of cisplatin (Cis) and Gef combination failed to show a therapeutic improvement likely due to compromised cellular influx of Cis with the Gef interference. To overcome the antagonism between Cis and Gef in anti-NSCLC therapy, here we demonstrated a self-targeted hyaluronan (HA) nanogel to facilitate the anticancer co-delivery by utilizing the HA's intrinsic targeting towards CD44, a receptor frequently overexpressed on lung cancer cells. The co-assembly between HA, Cis and Gef generated a HA/Cis/Gef nanogel of 177.8 nm, featuring a prolonged drug release. Unlike the Gef inhibited the Cis uptake, the HA/Cis/Gef nanogel efficiently facilitated the drug internalization through CD44-targeted delivery as verified by HA competition and CD44 knocking down in H1975 NSCLC model both in vitro and in vivo. Moreover, the HA/Cis/Gef nanogel significantly improved the anticancer efficacy and meanwhile diminished the side effects in reference to the combination of free Cis and Gef. This CD44-targeted HA/Cis/Gef nanogel provided a potent strategy to advance the platinum-based combination therapy towards optimized NSCLC therapy.

Structures and Single-Molecule Magnet Behavior of Dy3 and Dy4 Clusters Constructed by Different Dysprosium(III) Salts.

Using the Schiff base ligand H2L-pyra (N'-(2-hydroxybenzoyl)pyrazine-2-carbohydrazonamide) with multiple dentate sites, the trinuclear DyIII-based complex [Dy3(HL-pyra)2(L-pyra)2(CH3COO)3]·2H2O (1) was synthesized. By analyzing the fragmented assembly process and fine-tuning the bridging anions, complex [Dy4(HL-pyra)2(L-pyra)4(NO3)2(H2O)2]·8H2O (2) with different nuclear numbers was successfully synthesized. Magnetic studies demonstrated that 1 did not exhibit magnetic relaxation behavior under the external field; however, 2 exhibited zero-field single-molecule magnetic relaxation behavior with an effective energy barrier (Ueff) of 197.44 K. This is attributed to the improved anisotropy of the single ion after the normalization of the crystal structure, thus realizing the molecular magnetic switching. Moreover, magnetic dilution analysis of 2 demonstrated that the weak magnetic interaction between metal ions inhibited the occurrence of quantum tunneling of magnetization (QTM), resulting in high-performance single-molecule magnet (SMM) behavior. The reasons for the magnetic difference between these two complexes were analyzed using ab initio calculation and magneto-structural correlations. This study provides a reasonable prediction of the ideal configuration of the approximately parallelogram DyIII-based SMMs, thus offering an effective approach for synthesizing Dy4 complexes with excellent properties.

Derived Neutrophils to Lymphocyte Ratio Predicts Survival Benefit from TPF Induction Chemotherapy in Local Advanced Oral Squamous Cellular Carcinoma.

BACKGROUND: This study aimed to evaluate the derived neutrophil to lymphocyte ratio (dNLR) in predicting the prognosis of patients with locally advanced oral squamous cell carcinoma (LAOSCC) and to assess the survival benefits from docetaxel, cisplatin, and 5-fluorouracil (5-FU) (TPF) induction chemotherapy (IC). METHODS: Patients from a phase III trial involving TPF IC in stage III/IVA OSCC patients (NCT01542931) were enrolled. Receiver operating characteristic curves were constructed, and the area under the curve was computed to determine dNLR cutoff points. Kaplan-Meier survival estimates and Cox proportional hazards models were used for longitudinal analysis. RESULTS: A total of 224 patients were identified (median age: 55.4 years; range: 26 to 75 years; median follow-up: 90 months; range: 3.2 to 93 months). The cutoff point for the dNLR was 1.555. Multivariate analysis showed that the dNLR was an independent negative predictive factor for survival (overall survival (OS): hazard ratio (HR) = 1.154, 95% confidence interval (CI): 1.018-1.309, p = 0.025; disease-free survival (DFS): HR = 1.123, 95% CI: 1.000-1.260, p = 0.050; local recurrence-free survival (LRFS): HR = 1.134, 95% CI: 1.002-1.283, p = 0.047; distant metastasis-free survival (DMFS): HR = 1.146, 95% CI: 1.010-1.300, p = 0.035). A low dNLR combined with cTNM stage III disease predicted benefit from TPF IC for the patients [OS (χ2 = 4.674, p = 0.031), DFS (χ2 = 7.134, p = 0.008), LRFS (χ2 = 5.937, p = 0.015), and DMFS (χ2 = 4.832, p = 0.028)]. CONCLUSIONS: The dNLR is an independent negative predictive factor in LAOSCC patients. Patients with cTNM stage III disease and a low dNLR can benefit from TPF IC.

Contamination Status and Serotypes Distribution of Salmonella in Food in Yantai City, China: A 14-Year Continuous Monitoring Study.

Salmonella is a foodborne zoonotic pathogen that threatens food safety and public health. However, few people have conducted long-term and systematic studies on Salmonella contamination in food in Yantai City. In order to investigate the situation of Salmonella contamination in food and improve the ability of early warning and control of foodborne diseases, a total of 3420 samples from 20 categories were collected from 13 monitoring points in Yantai City, from 2010 to 2023. The difference in detection rate and bacterial strain of different monitoring points, different types, and different sources of samples was compared. Of the 3420 samples, 80 were positive with a detection rate of 2.34%. Salmonella detection rates were significantly different for samples collected at different monitoring sites. Salmonella was detected only in meat and meat products and catering food, and none of the other types were detected. The detection rate of Salmonella was higher in raw animal meat and raw poultry. Samples collected at the market stage had the highest detection rate (5.81%), and there was a significant difference in detection rate between samples from different sources (χ2 = 36.93, p < 0.05). Eighty-one strains of Salmonella were detected out of 3420 samples (2 different strains were detected in 1 positive sample). The serological test identified 8 groups and 27 serotypes. The dominant serum groups were group B 30.86% (25/81), group E1 23.46% (19/81), and group D 16.05% (13/81). The main dominant serotypes were Salmonella give 17.28% (14/81), Salmonella enteritidis 16.05% (13/81), and Salmonella derby 13.58% (11/81). Meat and meat products and catering food were the main food products contaminated with Salmonella. The resulting secondary contamination is the hidden threat of foodborne diseases and should be given sufficient attention.

Integrating ChatGPT in Orthopedic Education for Medical Undergraduates: Randomized Controlled Trial.

BACKGROUND: ChatGPT is a natural language processing model developed by OpenAI, which can be iteratively updated and optimized to accommodate the changing and complex requirements of human verbal communication. OBJECTIVE: The study aimed to evaluate ChatGPT's accuracy in answering orthopedics-related multiple-choice questions (MCQs) and assess its short-term effects as a learning aid through a randomized controlled trial. In addition, long-term effects on student performance in other subjects were measured using final examination results. METHODS: We first evaluated ChatGPT's accuracy in answering MCQs pertaining to orthopedics across various question formats. Then, 129 undergraduate medical students participated in a randomized controlled study in which the ChatGPT group used ChatGPT as a learning tool, while the control group was prohibited from using artificial intelligence software to support learning. Following a 2-week intervention, the 2 groups' understanding of orthopedics was assessed by an orthopedics test, and variations in the 2 groups' performance in other disciplines were noted through a follow-up at the end of the semester. RESULTS: ChatGPT-4.0 answered 1051 orthopedics-related MCQs with a 70.60% (742/1051) accuracy rate, including 71.8% (237/330) accuracy for A1 MCQs, 73.7% (330/448) accuracy for A2 MCQs, 70.2% (92/131) accuracy for A3/4 MCQs, and 58.5% (83/142) accuracy for case analysis MCQs. As of April 7, 2023, a total of 129 individuals participated in the experiment. However, 19 individuals withdrew from the experiment at various phases; thus, as of July 1, 2023, a total of 110 individuals accomplished the trial and completed all follow-up work. After we intervened in the learning style of the students in the short term, the ChatGPT group answered more questions correctly than the control group (ChatGPT group: mean 141.20, SD 26.68; control group: mean 130.80, SD 25.56; P=.04) in the orthopedics test, particularly on A1 (ChatGPT group: mean 46.57, SD 8.52; control group: mean 42.18, SD 9.43; P=.01), A2 (ChatGPT group: mean 60.59, SD 10.58; control group: mean 56.66, SD 9.91; P=.047), and A3/4 MCQs (ChatGPT group: mean 19.57, SD 5.48; control group: mean 16.46, SD 4.58; P=.002). At the end of the semester, we found that the ChatGPT group performed better on final examinations in surgery (ChatGPT group: mean 76.54, SD 9.79; control group: mean 72.54, SD 8.11; P=.02) and obstetrics and gynecology (ChatGPT group: mean 75.98, SD 8.94; control group: mean 72.54, SD 8.66; P=.04) than the control group. CONCLUSIONS: ChatGPT answers orthopedics-related MCQs accurately, and students using it excel in both short-term and long-term assessments. Our findings strongly support ChatGPT's integration into medical education, enhancing contemporary instructional methods. TRIAL REGISTRATION: Chinese Clinical Trial Registry Chictr2300071774; https://www.chictr.org.cn/hvshowproject.html ?id=225740&v=1.0.

A Membrane-Confined Signal Amplification Strategy for Sensitive Monitoring of Extracellular Enzymatic Activity Upon Drug Stimulus.

Extracellular enzymes are not only strongly correlated with disease development but also play critical roles in modulating immune responses. Therefore, real-time monitoring of extracellular enzymatic activity can afford straightforward insights into their spatiotemporal dynamics upon drug stimulus, and provide promising tools to unravel their key roles in modulating the cell signaling. Although DNA-based sensing probes have been frequently developed for the detection of a variety of biomolecules, there still lacks a modular design strategy for amplified imaging of extracellular enzymatic activity associated with live cells. Herein, we developed an enzymatically triggerable signal amplification strategy for real-time dynamic imaging of extracellular enzyme activity through a cell membrane-confined hybrid chain reaction (HCR). We demonstrated that, by modifying the initiator DNA with enzyme-specific incision sites and cholesterol tail, extracellular enzyme-trigged HCR could be fulfilled on the surface of the cellular membrane, facilitating amplified detection of extracellular enzymatic activity. Dynamic monitoring of enzyme secretion of cancer cells upon stimulus or macrophage cells upon inflammation challenge has also been achieved. We envision that the design strategy could provide valuable information for dissecting the role of extracellular enzymes in modulating cell responses to drug treatment.

A separation-free paper-based hydrogel device for one-step reactive oxygen species determination by a smartphone.

Paper-based analytical devices (PADs) are very convenient for determining biomarkers in point-of-care (POC) diagnosis while requiring sample pre-treatment or impurity separation. This study reports a novel hydrogel-coupled, paper-based analytical device (PAD) for separation-free H2O2 colorimetric detection in both aqueous solution and cell lysis with sample-to-answer analysis by directly loading into the sample test zone. By encapsulating an inorganic mimic enzyme and chromogenic substrate into the sodium alginate (SA) hydrogel, amplification of the color signal after catalyzing the substrate could be achieved. Taking advantage of the nanoscale porous structure of the hydrogel and the lateral flow channel of the PAD, large interference fragments or bio-macromolecules are prevented from diffusing into the chromogenic reaction, whereas the small target molecules enter the sensing region to trigger the catalytic reaction. This method demonstrated a rapid and accurate analysis with a limit of detection as low as 0.06 mM and detection selectivity. Our proposed device requires no enzyme and is separation-free, portable, easy-to-fabricate, and low-cost, and may offer a platform for quantitative or qualitative analysis of other analytes in body fluids for POC applications.

A two-center randomized controlled trial of a repairing mask as an adjunctive treatment for mild to moderate rosacea.

OBJECTIVE: To investigate the efficacy and safety of a repairing mask as an adjunctive treatment for skin barrier maintenance of mild to moderate rosacea. METHODS: Patients with rosacea were recruited in this dual center randomized controlled trial from November 2019 to December 2021. A total of 64 patients were included and randomized into two groups at a ratio of 3:1 into a mask group (n = 47) and a control group (n = 17). Patients in the mask group received treatment with Dr. Yu Centella asiatica repairing facial mask three times weekly for a duration of 6 weeks. All participants were instructed to continue their regimen of 50 mg oral minocycline twice daily and to apply Dr. Yu Intensive Hydrating Soft Cream twice daily. The primary endpoint of this study was the Investigator Global Assessment (IGA) score. RESULTS: A total of 54 patients completed this trial, with 41 in the mask group and 13 in the control group. After using this facial mask for 3 and 6 weeks, the IGA, facial skin dryness, facial flushing, and severity of skin lesion in the mask group showed significantly improvement (p < 0.05). Moreover, the change in the delta degree of skin flushing was significantly higher than that in the control group (p = 0.037). Throughout the study, no adverse events were reported in either group of participants. CONCLUSION: The Dr. Yu Centella asiatica repairing facial mask, as an adjunctive treatment of rosacea, appears to effectively repair and protect the skin barrier, alleviate cutaneous symptoms of rosacea, and is both efficacious and safe for patient use.

Geriatric nutritional risk index and mortality from all-cause, cancer, and non-cancer in US cancer survivors: NHANES 2001-2018.

Background: Malnutrition is strongly correlated with worsened treatment outcomes, reduced standard of living, and heightened mortality rates among individuals with cancer. Our research explores how the Geriatric Nutritional Risk Index (GNRI), a measure of nutritional status, relates to all-cause mortality, cancer-specific, and non-cancer mortality among middle-aged and older adult cancer patients. Methods: We enrolled 3,253 participants aged 40 and above who were diagnosed with cancer. The data was obtained from the National Health and Nutrition Examination Survey (NHANES) dataset covering the period from 2001 to 2018, with a median follow-up duration of 83 months. According to the GNRI levels, patients in the study were classified into two distinct groups: the group with a low GNRI (<98) and the group with a high GNRI (≥ 98). We conducted a Kaplan-Meier survival analysis to assess how survival rates vary with different nutritional conditions. Multivariable Cox regression analyses were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality, as well as cancer-specific and non-cancer-related mortality. Restricted cubic spline (RCS) analyses and subgroup evaluations were performed to augment the robustness and validity of our findings. Results: A total of 1,171 deaths were documented, with 383 attributed to cancer, and 788 from other causes. After adjusting for potential confounders, the analysis demonstrated that, within a specified range, an elevation in the GNRI is inversely associated with mortality from all causes, cancer-specific, and non-cancer causes. Moreover, Kaplan-Meier survival curves for all-cause, cancer-specific, and non-cancer mortality distinctly showed a more pronounced decrease in survival rates among individuals in the low GNRI group (<98). Notably, the restricted cubic spline regression model (RCS) revealed statistically significant non-linear associations between GNRI scores and mortality rates. The P-values were ≤0.001 for both all-cause and non-cancer mortality, and 0.024 for cancer-specific mortality. Conclusion: Our study conclusively demonstrated a robust correlation between GNRI scores and mortality rates among cancer patients, encompassing all-cause mortality as well as specific mortality related to both cancerous and non-cancerous causes. The GNRI may be a valuable prognostic tool for predicting cancer mortality outcomes, offering insights that may inform nutritional management and influence the clinical treatment strategies for cancer survivors.

Projected Impact of Nonpharmacologic Management of Stage 1 Hypertension Among Lower-Risk US Adults.

BACKGROUND: The 2017 American College of Cardiology/American Heart Association blood pressure guideline classified 31 million US adults as having stage 1 hypertension and recommended clinicians provide counseling on behavioral change to the low-risk portion of this group. However, nationwide reductions in cardiovascular disease (CVD) and associated health care expenditures achievable by nonpharmacologic therapy remain unquantified. METHODS: We simulated interventions on a target population of US adults aged 35 to 64 years, identified from the 2015-2018 National Health and Nutrition Examination Survey, with low-risk stage 1 systolic hypertension: that is, untreated systolic blood pressure 130 to 139 mm Hg with diastolic BP <90 mm Hg; no history of CVD, diabetes, or chronic kidney disease; and a low 10-year risk of CVD. We used meta-analyses and trials to estimate the effects of population-level behavior modification on systolic blood pressure. We assessed the extent to which restricting intervention to those in regular contact with clinicians might prevent the delivery of nonpharmacologic therapy. RESULTS: Controlling systolic blood pressure to <130 mm Hg among the 8.8 million low-risk US adults with stage 1 hypertension could prevent 26 100 CVD events, avoid 2900 deaths, and save $1.7 billion in total direct health care costs over 10 years. Adoption of the Dietary Approaches to Stop Hypertension diet could prevent 28 000 CVD events. Other nonpharmacologic interventions could avert between 3800 and 19 500 CVD events. However, only 51% of men and 75% of women regularly interacted with clinicians for counseling opportunities. CONCLUSIONS: Among low-risk adults with stage 1 hypertension, substantial benefits to cardiovascular health could be achieved through public policy that promotes the adoption of nonpharmacologic therapy.

Machine Learning-Based Predictive Modeling of Diabetic Nephropathy in Type 2 Diabetes Using Integrated Biomarkers: A Single-Center Retrospective Study.

Purpose: Diabetic nephropathy (DN), a major complication of diabetes mellitus, significantly impacts global health. Identifying individuals at risk of developing DN is crucial for early intervention and improving patient outcomes. This study aims to develop and validate a machine learning-based predictive model using integrated biomarkers. Methods: A cross-sectional analysis was conducted on a baseline dataset involving 2184 participants without DN, categorized based on their development of DN over a follow-up period of 36 months: DN (n=1270) and Non-DN (n=914). Various demographic and clinical parameters were analyzed. The findings were validated using an independent dataset comprising 468 participants, with 273 developing DN and 195 remaining as Non-DN over the follow-up period. Machine learning algorithms, alongside traditional descriptive statistics and logistic regression were used for statistical analyses. Results: Elevated levels of serum creatinine, urea, and reduced eGFR, alongside an increased prevalence of retinopathy and peripheral neuropathy, were prominently observed in those who developed DN. Validation on the independent dataset further confirmed the model's robustness and consistency. The SVM model demonstrated superior performance in the training set (AUC=0.79, F1-score=0.74) and testing set (AUC=0.83, F1-score=0.82), outperforming other models. Significant predictors of DN included serum creatinine, eGFR, presence of diabetic retinopathy, and peripheral neuropathy. Conclusion: Integrating machine learning algorithms with clinical and biomarker data at baseline offers a promising avenue for identifying individuals at risk of developing diabetic nephropathy in type 2 diabetes patients over a 36-month period.

Association between life's essential 8 and frailty status among cancer survivors in the United States: a cross-sectional analysis.

BACKGROUND: Frailty not only affects disease survival but also impacts the long-term function and quality life of all adults diagnosed with and/or treated for cancer.The American Heart Association has introduced Life's Essential 8 (LE8) as a novel metric for assessing cardiovascular health. Currently, LE8's application in evaluating the frailty of cancer survivors remains unreported. This research seeks to explore the connection between LE8 scores and frailty levels in cancer survivors across the United States, thereby addressing a significant void in existing studies. METHODS: This study analyzed data from cancer survivors enrolled in the National Health and Nutrition Examination Surveys (NHANES) spanning the years 2005 to 2018, providing a comprehensive dataset. Multivariable logistic regression models were used to examine the linkage between LE8 rankings and frailty condition in cancer survivors. Furthermore, the study delved deeper into this correlation using restricted cubic spline (RCS) curves and subgroup analyses. RESULTS: In the fully adjusted model, an increased LE8 level was closely associated with a reduced odds ratio of frailty among cancer survivors, with an OR of 0.95 (95% CI: 0.94-0.96, p < 0.0001).This pattern persisted across different categorizations of LE8 into low, moderate, and high groups, demonstrating a consistent trend. The analysis revealed a non-linear relationship between LE8 scores and frailty status, further supporting a straightforward association (p-value for non-linearity = 0.0729). CONCLUSION: Studies have found that the higher the LE8 score, the less likely a cancer patient is to develop debilitating symptoms.This indicates that the LE8 scores may provide an opportunity for interventions aimed at improving the prognosis of cancer patients.

High-resolution vasomotion analysis reveals novel arteriole physiological features and progressive modulation of cerebral vascular networks by stroke.

Spontaneous cerebral vasomotion, characterized by ∼0.1 Hz rhythmic contractility, is crucial for brain homeostasis. However, our understanding of vasomotion is limited due to a lack of high-precision analytical methods to determine single vasomotion events at basal levels. Here, we developed a novel strategy that integrates a baseline smoothing algorithm, allowing precise measurements of vasodynamics and concomitant Ca2+ dynamics in mouse cerebral vasculature imaged by two-photon microscopy. We identified several previously unrecognized vasomotion properties under different physiological and pathological conditions, especially in ischemic stroke, which is a highly harmful brain disease that results from vessel occlusion. First, the dynamic characteristics between SMCs Ca2+ and corresponding arteriolar vasomotion are correlated. Second, compared to previous diameter-based estimations, our radius-based measurements reveal anisotropic vascular movements, enabling a more precise determination of the latency between smooth muscle cell (SMC) Ca2+ activity and vasoconstriction. Third, we characterized single vasomotion event kinetics at scales of less than 4 seconds. Finally, following pathological vasoconstrictions induced by ischemic stroke, vasoactive arterioles entered an inert state and persisted despite recanalization. In summary, we developed a highly accurate technique for analyzing spontaneous vasomotion, and our data suggested a potential strategy to reduce stroke damage by promoting vasomotion recovery.

Inducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability.

Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, boasts significant potential for therapeutic intervention in cardiovascular dysfunctions. However, its impact on regulating fibrosis remains unexplored. This study aims to elucidate the role and mechanism of FGF13 on cardiac fibrosis. Here, we show that following transverse aortic constriction (TAC) surgery, interstitial fibrosis and collagen content increase in mice, along with reduced ejection fraction and fractional shortening, augmented heart mass. However, following Fgf13 deletion, interstitial fibrosis is decreased, ejection fraction and fractional shortening are increased, and heart mass is decreased, compared with those in the TAC group. Mechanistically, incubation of cardiac fibroblasts with transforming growth factor ß (TGFß) increases the expressions of types I and III collagen proteins, as well as α-smooth muscle actin (α-SMA) proteins, and enhances fibroblast proliferation and migration. In the absence of Fgf13, the expressions of these proteins are decreased, and fibroblast proliferation and migration are suppressed, compared with those in the TGFß-stimulated group. Overexpression of FGF13, but not FGF13 mutants defective in microtubule binding and stabilization, rescues the decrease in collagen and α-SMA protein and weakens the proliferation and migration function of the Fgf13 knockdown group. Furthermore, Fgf13 knockdown decreases ROCK protein expression via microtubule disruption. Collectively, cardiac Fgf13 knockdown protects the heart from fibrosis in response to haemodynamic stress by modulating microtubule stabilization and ROCK signaling pathway.

Co-assembly of cisplatin and dasatinib in hyaluronan nanogel to combat triple negative breast cancer with reduced side effects.

Treatment for triple negative breast cancer (TNBC) remains a huge challenge due to the lack of targeted therapeutics and tumor heterogenicity. Cisplatin (Cis) have demonstrated favorable therapeutic response in TNBC and thus is used together with various kinase inhibitors to fight the heterogenicity of TNBC. The combination of Cis with SRC inhibitor dasatinib (DAS) has shown encouraging anti-TNBC efficacy although the additive toxicity was commonly observed. To overcome the severe side effects of this Cis involved therapy, here we co-encapsulated Cis and DAS into a self-assembled hyaluronan (HA) nanogel (designated as HA/Cis/DAS (HCD) nanogel) to afford the TNBC targeted delivery by using the 4T1 mouse model. The acquired HCD nanogel was around 181 nm in aqueous solution, demonstrating the pharmacological activities of both Cis and DAS. Taking advantages of HA's targeting capability towards CD44 that is overexpressed on many TNBC cells, the HCD could well maintain the anticancer efficacy of the Cis and DAS combination, significantly increase the maximum tolerated dose and relieve the renal toxicity in vivo. The current HCD nanogel provides a potent strategy to improve the therapeutic outcome of Cis and DAS combination and thus representing a new targeted treatment option for TNBC.

Quantum-level investigation of air decomposed pollutants gas sensor (Pd-modified g-C3N4) influenced by micro-water content.

In the electrical industry, there are many hazardous gases that pollute the environment and even jeopardize human health, so timely detection and effective control of these hazardous gases is of great significance. In this work, the gas-sensitive properties of Pd-modified g-C3N4 interface for each hazardous gas molecule were investigated from a microscopic viewpoint, taking the hazardous gases (CO, NOx) that may be generated in the power industry as the detection target. Then, the performance of Pd-modifiedg-C3N4 was evaluated for practical applications as a gas sensor material. Novelly, an unconventional means was designed to briefly predict the effect of humidity on the adsorption properties of this sensor material. The final results found that Pd-modified g-C3N4 is most suitable as a potential gas-sensitizing material for NO2 gas sensors, followed by CO. Interestingly, Pd-modified g-C3N4 is less suitable as a potential gas-sensitizing material for NO gas sensors, but has the potential to be used as a NO cleaner (adsorbent). Unconventional simulation explorations of humidity effects show that in practical applications Pd-modified g-C3N4 remains a promising material for gas sensing in specific humidity environments. This work reveals the origin of the excellent properties of Pd-modified g-C3N4 as a gas sensor material and provides new ideas for the detection and treatment of these three hazardous gases.