Tandem Targeting and Dual Aggregation of an AIEgen for Enhanced Near-Infrared Fluorescence Imaging of Tumors.

Near-infrared (NIR) aggregation-induced emission luminogens (AIEgens) are excellent probes for tumor imaging, but there still is space to improve their imaging specificity and sensitivity. In this work, a strategy of tandem targeting and dual aggregation of an AIEgen is proposed to achieve these two purposes. An AIEgen, ß-tBu-Ala-Cys(StBu)-Lys(Biotin)-Pra(QMT)-CBT (Ala-Biotin-QMT), is designed to tandem target the biotin receptor and leucine aminopeptidase of a cancer cell and thereafter undergo CBT-Cys click reaction-mediated dual aggregations in the cell. Experimental results show that Ala-Biotin-QMT renders 4.8-fold and 7.9-fold higher NIR fluorescence signals over those in the "biotin + LAP inhibitor"-treated control groups in living HepG2 cells and HepG2 tumor-bearing mice, respectively. We anticipate that Ala-Biotin-QMT, which has the tandem targeting and dual aggregation property to simultaneously achieve enhanced tumor enrichment and fluorescence onset, could be applied for accurate cancer diagnosis in the clinic in the future.

SGLT2 inhibitor promotes ketogenesis to improve MASH by suppressing CD8+ T cell activation.

During the progression of metabolic dysfunction-associated steatohepatitis (MASH), the accumulation of auto-aggressive CD8+ T cells significantly contributes to liver injury and inflammation. Empagliflozin (EMPA), a highly selective inhibitor of sodium-glucose co-transporter 2 (SGLT2), exhibits potential therapeutic benefits for liver steatosis; however, the underlying mechanism remains incompletely elucidated. Here, we found that EMPA significantly reduced the hepatic accumulation of auto-aggressive CD8+ T cells and lowered granzyme B levels in mice with MASH. Mechanistically, EMPA increased ß-hydroxybutyric acid by promoting the ketogenesis of CD8+ T cells via elevating 3-hydroxybutyrate dehydrogenase 1 (Bdh1) expression. The ß-hydroxybutyric acid subsequently inhibited interferon regulatory factor 4 (Irf4), which is crucial for CD8+ T cell activation. Furthermore, the ablation of Bdh1 in T cells aggravated the manifestation of MASH and hindered the therapeutic efficacy of EMPA. Moreover, a case-control study also showed that SGLT2 inhibitor treatment repressed CD8+ T cell infiltration and improved liver injury in patients with MASH. In summary, our study indicates that SGLT2 inhibitors can target CD8+ T cells and may be an effective strategy for treating MASH.

Associations Between Serum Vitamin A Levels in Early Pregnancy and the Risk of Gestational Diabetes Mellitus.

Background: The relationship between vitamin A levels and gestational diabetes mellitus (GDM) is not well understood, and prospective studies are lacking. Methods: This was a prospective, longitudinal study. A total of 391 women in early pregnancy were recruited between October and December 2018 at Shunyi District Maternal and Child Health Hospital (Beijing, China). Serum vitamin A concentration was measured at enrollment. GDM was diagnosed on the basis of a 75 g oral glucose-tolerance test at 24-28 weeks of follow-up. Logistic regression was used for the analysis. Results: None of the subjects in the cohort had vitamin A deficiency or excess. At the follow-up, 76 participants had developed GDM. Participants who developed GDM were older and had higher body mass index, fasting insulin, HbA1c, fasting glucose, homeostasis model assessment for insulin resistance, triglyceride, low-density lipoprotein cholesterol, and high-sensitivity CRP levels, as well as higher serum vitamin A levels at baseline. On logistic multivariate analysis, higher vitamin A was positively associated with higher risk of GDM. The adjusted OR was 2.85 (95% CI 1.04-7.80, P=0.042) for Q4 versus Q1 and 1.59 (95% CI 1.11-2.28, P=0.011) for every 1 SD increase in serum vitamin A levels. In participants within the vitamin A reference range (0.33-0.78 mg/L), the positive association also maintained significance. Conclusion: Higher serum vitamin A levels were associated with higher GDM risks, even within the reference range. The results and possible mechanisms need to be further verified and clarified.

First Report of Didymella uniseptata Causing Leaf Spot on Taraxacum mongolicum in China.

Dandelion (Taraxacum mongolicum), belonging to the Asteraceae family, is one of the main associated species in the alpine meadow, and is famous for its both feeding and medicinal values (Lin et al. 2022; Wang et al. 2022). In September 2021 (vigorous growth period), a newly emerging leaf spot disease of T. mongolicum were observed on natural grassland in Ruoergai County, Aba (Ngawa) Tibetan and Qiang Autonomous Prefect, China (33°59'51'' N, 102°44'57'' E, alt. 3414 m). Leaf disease incidence was ranged from 10% to 15%. The symptoms appeared as brown to dark brown, circular or irregular, sunken spots; eventually, the infected sites of leaves formed a hole in the middle position of lesions. For isolation, 21 tissue pieces (5mm × 5mm) from 7 symptomatic leaf samples of 4 different plants were surface sterilized with 70% ethanol for 30 s and rinsed three times with sterilized distilled water. Then, these tissues were placed on potato dextrose agar (PDA) at 25°C and incubated in the dark for 2 to 7 days. Finally, six pure Didymella strains with consistent colony characteristics were obtained from hyphal tips as described by Xue et al. (2023). Colonies on PDA were brown to black with concentric circles, and abundant black pycnidia were visible; reverse similar in color. Conidia were ellipsoidal, ovoid, hyaline, 0 to 1-septate, 4.07 to 8.67 × 2.74 to 5.35 µm (average 3.60 × 6.55 µm; n = 50). Seven-week-old healthy plants were obtained by growing T. mongolicum seeds in pots (two plants per pot). The six pure Didymella strains were subsequently used to inoculate healthy plants as follows: for each strain, eight pots were spray inoculated with a mycelial suspension of about 4 × 104 CFU/ml, referring to our previous method (Xue et al. 2023). In addition, eight pots considered as non-inoculated controls were sprayed with sterilized distilled water. All pots were individually covered with transparent polyethylene bags for 5 days to maintain high relative humidity and placed in a greenhouse at 23 to 29°C. After incubation for 10 days, the typical symptoms consisted of brown to dark brown, sunken spots, which were similar to those previously observed in nature grassland; however, symptoms were not observed on the non-inoculated plants (controls). The same fungus was reisolated from the lesions and confirmed by the morphological and molecular methods described in this note, thus fulfilling Koch's postulates. To further identify this fungal pathogen, ITS-rDNA, and two other protein-coding genes (rpb2 and tub2) of the representative strain REG28 were amplified with primers described by Chen et al. (2022). Sequences were deposited in GenBank (PP385777 for ITS, PP781948 for rpb2, and PP781947 for tub2). A maximum likelihood (RAxML) phylogenetic tree based on the combined ITS, rpb2, and tub2 alignments showed REG28, and ex-type CGMCC 3.20069 of D. uniseptata (Chen et al. 2022) formed a subclade with 100% bootstrap support (Fig. S1). The causal agent of this disease was confirmed as D. uniseptata by the morphological, molecular, and pathogenic features described above. Recently, D. macrophylla has been reported as the first record on T. officinale in Russia (Gomzhina et al. 2020). To our knowledge, this is the first report of D. uniseptata causing leaf spots on T. mongolicum worldwide. This information will be useful for the diagnosis, detection, pathogen identification and future control of this disease on T. mongolicum in natural grassland.

Optimizing a national examination for medical undergraduates via modern automated test assembly approaches.

BACKGROUND: Automated test assembly (ATA) represents a modern methodology that employs data science optimization on computer platforms to automatically create test form, thereby significantly improving the efficiency and accuracy of test assembly procedures. In the realm of medical education, large-scale high-stakes assessments often necessitate lengthy tests, leading to elevated costs in various dimensions (such as examinee fatigue and expenses associated with item development). This study aims to augment the design of the medical education assessments by leveraging modern ATA approaches. METHODS: To achieve the objective, a four-step process employing psychometric methodologies was used to calibrate and analyze the item pool of the Standardized Competence Test for Clinical Medicine Undergraduates (SCTCMU), a nationwide summative test comprising 300 multiple-choice questions (MCQ) in China. Subsequently, two modern ATA approaches were employed to determine the optimal item combination, accounting for both statistical and content requirements specified in the test blueprint. The qualities of the assembled test form, generated using modern ATA approaches, underwent meticulous evaluation. RESULTS: Through an exploration of the psychometric properties of the SCTCMU as a foundational step, the evaluation revealed commendable quality in the item properties. Furthermore, the evaluation of the quality of assembled test form using modern ATA approaches indicated the ability to ascertain the optimal test length within the predefined measurement precision. Specifically, this investigation demonstrates that the application of modern ATA approaches can substantially reduce the test length of assembled test form, while simultaneously maintaining the required statistical and content standards specified in the test blueprint. CONCLUSIONS: This study harnessed modern ATA approaches to facilitate the automatic construction of test form, thereby significantly enhancing the efficiency and precision of test assembly procedures. The utilization of modern ATA approaches offers medical educators a valuable tool to enhance the efficiency and cost-effectiveness of medical education assessment.

Comparative analysis of atherosclerotic cardiovascular disease burden between ages 20-54 and over 55 years: insights from the Global Burden of Disease Study 2019.

BACKGROUND: To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. METHODS: We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20-54 and > 55 years from 1990-2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. RESULTS: From 1990-2019, the global prevalence rates of IHD, IS, and PAD in the 20-54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20-54 years group than in the > 55 years group. For PAD, DALYs among those aged 20-54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. CONCLUSIONS: The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.

Enhancing Postanesthesia Care Unit Management Based on Noise Reduction Strategies Grounded in Comfort Theory.

PURPOSE: To explore the management improvement measures and application effects of reducing noise in postanesthesia care unit (PACU) based on Comfort Theory. DESIGN: Randomized controlled clinical trial. METHODS: A total of 1,300 patients who underwent general anesthesia or combined nerve block anesthesia and were transferred to the PACU in May and August 2021 were divided into a control group (630 cases) and a study group (670 cases) based on time. The control group received routine PACU management, and management based on Comfort Theory to reduce the noise in the PACU was implemented with the study group, including physiological comfort, psychological and spiritual comfort, social and cultural comfort, and environmental comfort. The overall noise level in PACU, retention time in PACU, incidence of nursing adverse events, and patient satisfaction were compared before and after implementation. FINDINGS: In the observation group, the noise values of the four time periods in the PACU were significantly decreased, the retention time was (59.92 ± 22.0) minutes, the incidence of nursing adverse events and vomiting was 0.1%, and the patient satisfaction was 99.8%, which were significantly better than those in the control group, and the differences were statistically significant (P < .05). CONCLUSIONS: The management of noise reduction in PACU based on Comfort Theory can significantly reduce the noise level in PACU, effectively shorten the PACU retention time, reduce the incidence of nursing adverse events, and improve the nursing satisfaction of patients.

Herbal Medicine-Derived Exosome-Like Nanovesicles: A Rising Star in Cancer Therapy.

Plant-derived exosome-like nanovesicles (PDNVs) are small nanoscale vesicles containing lipids, RNAs, proteins and some plant natural products secreted by plant cells. Over the last decade, PDNVs have garnered significant interest due to its exceptional therapeutic benefits in the treatment of various diseases. Herbal medicine, as a medicinal plant, plays an important role in the treatment of diseases including cancer. Especially in recent years, the function of herbal medicine derived exosome-like nanovesicles (HMDNVs) in the treatment of cancer has been widely concerned, and has become a research hotspot of nanomedicine. In this review, the biological characteristics, functions and the therapeutic advantages of PDNVs are reviewed, as well as the recent achievements and research progress of HMDNVs in cancer treatment, demonstrating its enormous promise as a cancer therapy, and new insights are provided for future research and development of anti-tumor drugs.

Study on the Influence of Waste Rock Wool on the Properties of Cement Mortar under the Dual Fiber Effect of Polyvinyl Alcohol Fibers and Steel Fibers.

In this paper, the effect of waste rock-wool dosage on the workability, mechanical strength, abrasion resistance, toughness and hydration products of PVA and steel fiber-reinforced mortars was investigated. The results showed that the fluidity of the mortar gradually decreased with the increase in the dosage of waste rock wool, with a maximum reduction of 10% at a dosage of 20%. The higher the dosage of waste rock wool, the greater the reduction in compressive strength. The effect of waste rock wool on strength reduction decreases with increasing age. When the dosage of waste rock wool was 10%, the 28 days of flexural and compressive strengths were reduced by 4.73% and 10.59%, respectively. As the dosage of waste rock wool increased, the flexural-to-compressive ratio increased, and at 20%, the maximum value of 28 days of flexural-to-compressive ratio was 0.210, which was increased by 28.05%. At a 5% dosage, the abraded volume was reduced from 500 mm3 to 376 mm3-a reduction of 24.8%. Waste rock wool only affects the hydration process and does not cause a change in the type of hydration products. It promotes the hydration of the cementitious material system at low dosages and exhibits an inhibitory effect at high dosages.

Effects of ciprofol infusion on hemodynamics during induction and maintenance of anesthesia and on postoperative recovery in patients undergoing thoracoscopic lobectomy: Study protocol for a randomized, controlled trial.

INTRODUCTION: Ciprofol, a new candidate drug, is effective and safe for the maintenance of anesthesia in non-cardiothoracic and non-neurological elective surgery. However, few studies have been conducted on general anesthesia using ciprofol in patients undergoing thoracoscopic lobectomy. Therefore, this study aims to observe the effects of ciprofol on hemodynamics and on postoperative recovery in patients undergoing thoracoscopic lobectomy. METHODS AND ANALYSIS: This randomized controlled trial will include 136 patients aged 18-65 years undergoing elective thoracoscopic lobectomy between April 2023 and December 2024. The participants will be randomly assigned to the propofol or ciprofol group. The primary outcome to be assessed is the hemodynamic fluctuation during the induction and maintenance of anesthesia. The secondary outcomes involve quality of anesthesia induction and quality of recovery from anesthesia. The former includes TLOC (time to loss of consciousness), the use of vasoactive agents, the incidence of injection pain, body movement, muscle twitching and coughing during induction of anesthesia. The latter includes TROC (time to recovery of consciousness), post anesthesia care unit (PACU) time, incidence of postoperative nausea and vomiting (PONV), postoperative agitation, intraoperative awareness and quality of recovery (QoR) score. DISCUSSION: A number of clinical trials have confirmed that ciprofol, as a new sedative-hypnotic agent, has advantages of better tolerance, higher sedation satisfaction score, and lower incidence of adverse reactions, especially in reducing the incidence of injection pain. But considering that ciprofol was recently developed, limited data are available regarding its use for general anesthesia. This study aims to investigate the effects of ciprofol on hemodynamics and on postoperative recovery of patients undergoing thoracoscopic lobectomy. The results of this study may provide evidence for the safe application of ciprofol, a new choice of general anesthetic for thoracic surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT05664386).

Customizing Bayesian multivariate generalizability theory to mixed-format tests.

Mixed-format tests, which typically include dichotomous items and polytomously scored tasks, are employed to assess a wider range of knowledge and skills. Recent behavioral and educational studies have highlighted their practical importance and methodological developments, particularly within the context of multivariate generalizability theory. However, the diverse response types and complex designs of these tests pose significant analytical challenges when modeling data simultaneously. Current methods often struggle to yield reliable results, either due to the inappropriate treatment of different types of response data separately or the imposition of identical covariates across various response types. Moreover, there are few software packages or programs that offer customized solutions for modeling mixed-format tests, addressing these limitations. This tutorial provides a detailed example of using a Bayesian approach to model data collected from a mixed-format test, comprising multiple-choice questions and free-response tasks. The modeling was conducted using the Stan software within the R programming system, with Stan codes tailored to the structure of the test design, following the principles of multivariate generalizability theory. By further examining the effects of prior distributions in this example, this study demonstrates how the adaptability of Bayesian models to diverse test formats, coupled with their potential for nuanced analysis, can significantly advance the field of psychometric modeling.

Identification, Pathogenicity, and Fungicide Sensitivity of Colletotrichum Species Associated with Anthracnose on Italian Ryegrass in Southwestern China.

Italian ryegrass (Lolium multiflorum L.) is widely cultivated as an important forage worldwide because of its high nutritional value and good palatability. Anthracnose caused by Colletotrichum species was a common and new emerging disease of Italian ryegrass. In this study, 88 Colletotrichum isolates were collected from diseased leaves of Italian ryegrass planting regions in Sichuan, Chongqing and Guizhou provinces of southwestern China between 2019 and 2022. By pure culture technique, 15 representative single-spore isolates were obtained for further study. Multi-locus phylogenetic analysis coupled with morphological features showed that these isolates were finally identified as six new record species: C. cereale of the C. graminicola species complex, C. fioriniae and C. nymphaeae of the C. acutatum species complex, C. boninense and C. citricola of the C. boninense species complex, and C. nageiae. Pathogenicity tests indicated that all species could induce anthracnose symptoms; of these, C. cereale was more invasive than other species, followed by C. fioriniae, C. nageiae, C. citricola and C. boninense; C. nymphaeae was weakest pathogenic to Italian ryegrass plants (P ≤ 0.05). Fungicide sensitivity assays showed that iprodione, propineb and oxime·tebuconazole had strong inhibitory effect on the mycelial growth of six Colletotrichum species; in addition, azoxystrobin and fludioxonil also significantly inhibited the mycelial growth of C. nymphaeae and C. fioriniae, respectively. These results provide the basis for the diagnosis and detection in the field, pathogen identification and management of anthracnose on Italian ryegrass.

Influence of Different Types of Fillers on the Performance of PMMA-Based Low-Temperature Rapid Repair Mortar.

In order to further optimize the performance of PMMA (Polymethyl Methacrylate) repair mortar. In this paper, fly ash, talcum powder and wollastonite powder are used as fillers to modify the PMMA repair mortar. The effects of these three fillers on the working performance, mechanical performance and durability of PMMA repair mortar were explored. The study shows that the three fillers have good effect on the bond strength of the repair mortar, in which the fly ash has the best effect on the mechanical performance. The mechanical properties of PMMA repair mortar were best when the amount of fly ash was 60 phr (parts per hundred, representing the amount of the material added per hundred parts of PMMA). At this time, the 28 d compressive strength was 71.26 MPa and the 28 d flexural strength was 28.09 MPa, which increased by 13.31% and 15.33%, respectively. Wollastonite powder had the least negative effect on the setting time of the PMMA repair mortar. When the dosage of wollastonite powder was increased to 100 phr, the setting time was only extended from 65 min to 94 min. When the talc dosage was 60 phr, the best improvement in salt freezing resistance was achieved. After 100 cycles of salt freezing, the mass loss rate and strength loss rate decreased to 0.159% and 4.97%, respectively, which were 75.1% and 37.7% higher than that of the control group. The addition of all three fillers reduced the porosity and the proportion of harmful pores in the mortar. This study contributes to a comprehensive understanding how different types of fillers affect PMMA repair mortars, and it also provides theoretical support for the further development of low-temperature rapid repair mortars.

Effects of TCM external scalding therapy on spleen-stomach deficiency cold stomachache and inflammatory indexes.

OBJECTIVE: To determine the efficacy and safety of traditional Chinese medicine (TCM) external scalding therapy on spleen-stomach deficiency cold stomachache. METHODS: The medical records of 98 patients with spleen-stomach deficiency cold stomachache treated in the Affiliated Hospital of Jiangnan University from January 2019 to January 2020 were collected and analyzed retrospectively. Among them, 52 patients treated with western medicine were assigned to the control group, while the other 46 patients treated additionally with TCM external scalding therapy were assigned to the observation group. The two groups were compared in terms of serum gastrin (GAS), inflammatory factors and visual analogue scale (VAS) score, adverse reaction rate and symptom remission time. RESULTS: After treatment, the observation group showed a significantly lower GAS level than the control group (P<0.05), along with significantly lower serum levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) than the control group (all P<0.05). The observation group demonstrated significantly lower VAS score than the control group (P<0.05). The observation group experienced notably shorter remission time of dull epigastric pain, epigastric distension, fatigue and belching and acid reflux than the control group (all P<0.05), and a significantly lower incidence of adverse reactions was found in the observation group than that in the control group (P<0.05). Multivariate analysis revealed that history of alcoholism and treatment method were independent risk factors affecting patient outcomes (all P<0.05). CONCLUSION: TCM external scalding therapy has shown effectiveness in treating spleen-stomach deficiency cold stomachache. It alleviates stomachache symptoms and also reduces the occurrence of adverse reactions and inflammation, holding great potential for widespread adoption in clinical practice.

Near-infrared AIEgens for sulfatase imaging in breast cancer in vivo.

Aggregation-induced emission luminogens (AIEgens) enable highly sensitive and in situ visualization of sulfatase to benefit the early diagnosis of breast cancer (BC), but current sulfatase AIEgens always emit visible light (<650 nm). Herein, a near-infrared (NIR) AIEgen QMT-SFA is developed for sulfatase imaging in vivo. Hydrophilic QMT-SFA is cleaved by sulfatase to yield hydrophobic QMT-OH, which subsequently aggregates into nanoparticles to turn the AIE fluorescence "on", enabling sensitive sulfatase imaging in 4T1 cells and mouse models.

Turning bad into good: A medium-entropy double perovskite oxide with beneficial surface reconstruction for active and robust cathode of solid oxide fuel cells.

The cathodes of solid oxide fuel cells (SOFCs) often suffer from detrimental cation segregations and associated impurities poisoning, leading to insufficient electroactivity and poor stability. Here we developed a medium-entropy double perovskite GdBa(Co1.2Mn0.2Fe0.2Ni0.2Cu0.2)O5-δ (ME-GBCO) for promising SOFC cathode. The increased configuration entropy can effectively tailor the surface composition with in situ formed active BaCoO3-δ (BCO) species, rather than inert and deleterious BaOx segregation on parent GdBaCo2O5-δ (GBCO) surface. Accordingly, the layered ME-GBCO cathode with beneficial surface reconstruction exhibited not only high oxygen reduction activity but excellent durability against CO2 impurity, enabling it a very attractive cathode for intermediate temperature SOFCs (IT-SOFCs). Our study provides a new idea for development of efficient and durable cathodes via configurational entropy induced rational surface reconstruction.

The observation of atmospheric HONO by wet-rotating-denuder ion chromatograph in a coastal city: Performance and influencing factors.

Due to the significance of atmospheric HONO as a reservoir for radicals and the presence of substantial unknown sources of HONO, there is a pressing need for accurate and consistent measurement of its concentration. In this study, we compared the measurements obtained from the monitor for aerosols and gases in ambient air (MARGA) based on wet chemical method with those from the incoherent broadband cavity-enhanced absorption spectroscopy (IBBCEAS) based on optical method to assess the suitability of the MARGA instrument for accurate HONO detection. The diurnal patterns obtained by the two instruments are similar, with peaks at 8 a.m. and lows at 5 p.m. Over the course of the observation period, it was often observed that HONO concentrations recorded by the MARGA instrument consistently exceeded those obtained through the IBBCEAS technique, accounting for approximately 91.33% of the total observation time. Throughout the entire observation period, the R2 value between the two instruments was 0.49, indicating relatively good correlation. However, with a slope of only 0.27, it suggests poor agreement between the two instruments. Furthermore, the R2 and slopes between the two instruments vary with the seasons and day-night. The larger the quartile values of NO2, NH3, and BC, the greater the slopes of both MARGA and IBBCEAS instruments, and the higher the concentrations of NO2, NH3, and BC (indicator of semivolatile oxidizable hydrocarbons), the greater the differences between the two instruments, all indicating that NH3 may promote the reaction of NO2 with semivolatile oxidizable hydrocarbons to produce HONO. The O3 with its strong oxidizing properties may cause underestimation in the MARGA instrument by oxidizing NO2- to NO3- in the absorbing solution. It is challenging to derive a universal correction formula due to the interference of various chemical substances. Hence, MARGA should not be used for HONO research in the future.

Diminished levels of insulin-like growth factor-1 may be a risk factor for peripheral neuropathy in type 2 diabetes patients.

AIMS/INTRODUCTION: To investigate risk factors for diabetic peripheral neuropathy (DPN) and to explore the connection between insulin-like growth factor-1 (IGF-1) and DPN in individuals with type 2 diabetes. MATERIALS AND METHODS: A total of 790 patients with type 2 diabetes participated in a cross-sectional study, divided into two groups: those with DPN (DPN) and those without DPN (non-DPN). Blood samples were taken to measure IGF-1 levels and other biochemical markers. Participants underwent nerve conduction studies and quantitative sensory testing. RESULTS: Patients with DPN exhibited significantly lower levels of IGF-1 compared with non-DPN patients (P < 0.001). IGF-1 was positively correlated with the average amplitude of both motor (P < 0.05) and sensory nerves (P < 0.05), but negatively correlated with the vibration perception threshold (P < 0.05). No significant difference was observed between IGF-1 and nerve conduction velocity (P > 0.05), or the temperature detection threshold (P > 0.05). Multivariate regression analysis identified diabetes duration, HbA1c, and the low levels of IGF-1 as independent risk factors (P < 0.001). Receiver operating characteristic analysis determined that at 8 years duration of diabetes, 8.5% (69.4 mmol/mol) HbA1c and 120 ng/mL IGF-1, the optimal cut-off points, indicated DPN (P < 0.001). CONCLUSIONS: A reduction of IGF-1 in patients with DPN suggests a potential protective role against axon injury in large fiber nerves of type 2 diabetes patients.

A Membrane-Targeting Aggregation-Induced Emission Probe for Monitoring Lipid Droplet Dynamics in Ischemia/Reperfusion-Induced Cardiomyocyte Ferroptosis.

Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor is ischemia/reperfusion (I/R)-induced cardiomyocyte ferroptosis, marked by iron overload and lipid peroxidation. However, the impact of lipid droplet (LD) changes on I/R-induced cardiomyocyte ferroptosis is unclear. In this study, an aggregation-induced emission probe, TPABTBP is developed that is used for imaging dynamic changes in LD during myocardial I/R-induced ferroptosis. TPABTBP exhibits excellent LD-specificity, superior capability for monitoring lipophagy, and remarkable photostability. Molecular dynamics (MD) simulation and super-resolution fluorescence imaging demonstrate that the TPABTBP is specifically localized to the phospholipid monolayer membrane of LDs. Imaging LDs in cardiomyocytes and myocardial tissue in model mice with MIRI reveals that the LD accumulation level increase in the early reperfusion stage (0-9 h) but decrease in the late reperfusion stage (>24 h) via lipophagy. The inhibition of LD breakdown significantly reduces the lipid peroxidation level in cardiomyocytes. Furthermore, it is demonstrated that chloroquine (CQ), an FDA-approved autophagy modulator, can inhibit ferroptosis, thereby attenuating MIRI in mice. This study describes the dynamic changes in LD during myocardial ischemia injury and suggests a potential therapeutic target for early MIRI intervention.