Facile fabrication of a thermal/pH responsive IPN hydrogel drug carrier based on cellulose and chitosan through simultaneous dual-click strategy.

Herein, an interpenetrating network hydrogel (IPN-Gel) based on cellulose and chitosan was synthesized via simultaneous amino-anhydride and azide-alkyne click reaction in water in one pot. The samples were characterized by various analytical methods including FTIR, SEM, XRD, XPS, 1H NMR and so forth. The fabrication conditions were optimized by single factor experiments with water uptake (WU) and gel mass fraction (GMF) as two indexes. The WU and GMF of the IPN-Gel prepared under optimized conditions were 1192.37 % and 74.00 %, respectively. Its WU descended with the ascension in temperature, and first descended and then gradually ascended with the ascension in pH, confirming that the IPN-Gel had thermal/pH dual responsiveness. Using 5-Fu as a model drug, the release behavior of 5-Fu in IPN-Gel was explored. Its release behavior could be regulated by changing temperature and pH values, and it followed the Korsmeyer Peppas model. The viability of 4 T1 cells and HUVEC cells exceeded 80 % after 48 h of incubation at a high concentration of 200 µg/mL IPN-Gel, and hemolytic percentage was below the allowed limit of 5 %. The study provides a new strategy for the preparation of the IPN-Gel with biocompatibility, swelling reversibility and controllable drug release.

Association of FOXL2 and ERCC6 variants with premature ovarian insufficiency and their potential use in clinical IVF guidance.

Premature ovarian insufficiency (POI) is the main cause of infertility in women. Some cases of POI are thought to be caused by genetic defects and the clinical outcomes of these patients are unknown. Here, we performed whole-exome sequencing of the peripheral blood of a cohort of 55 subjects with POI and identified one heterozygous missense variant in FOXL2 (c.1045G>C; p.Arg349Gly) and two heterozygous missense variants in ERCC6 (c.379G>A; p.Val127Ile and c.4223A>C; p.Glu1408 Ala) in four POI patients. All of these heterozygous mutations were predicted to be deleterious and were parentally inherited from their heterozygous fathers. The mRNA and protein expression of FOXL2 and ERCC6 were absent or decreased in the patients. The patients carrying the variants of FOXL2 (c.1045G>C; p.Arg349Gly) and ERCC6 (c.379G>A; p.Val127Ile) failed to conceive in two and four assisted reproductive cycles, respectively. Another patient and her sister carrying the ERCC6 (c.4223A>C; p.Glu1408 Ala) variant achieved good clinical outcomes after assisted reproductive therapy. Our findings support the possible roles of FOXL2 and ERCC6 in POI and might contribute to the genetic counseling of POI patients.

Phylogeographic analysis of Y-chromosomal haplogroup C2a-M48-F8472, a minor paternal lineage of Han populations with possible ancestry of Xiongnu.

BACKGROUND: Y-chromosome haplogroup C2a-M48-F8472, a unique paternal line in the ancient Xiongnu population, is concentrated in the modern Han people. The most closely related lineage of this paternal lineage is mainly distributed in Tungusic-, Mongolic-, and Turkic-speaking populations. AIM: To investigate the formation process of this unique distribution state. SUBJECTS AND METHODS: In total, 36 sequences of haplogroup C2a-M48-F8472 were analysed to generate a revised phylogenetic tree with age estimation and to explore the geographic distribution pattern. RESULTS: The results suggested that northern China is likely the diffusion centre of this paternal haplogroup. This lineage is concentrated in the Liu clan () of Han populations and may have originated in the Tuge tribe () of Xiongnu populations. The initial expansion (∼2,600 years ago) and the second phase of expansion (∼1,570 years ago) of haplogroup C2a-M48-F8472 coincide with the earlier appearance and later disappearance of the Tuge tribe. As a sub-clade of M48, the history of F8472 suggested that ancient peoples related to Tungusic-speaking populations were intricately connected with the demographic history of populations in the Mongolian Plateau. CONCLUSION: The appearance of this paternal line in the Han population is helpful for understanding the mixed history of ancient and modern people in the Mongolian Plateau and Central China.

Propensity score matching analysis of early vs. delayed surgery for intertrochanteric fracture in older patients: a retrospective multicenter cohort study of 7414 patients with a mean 4-year follow up.

BACKGROUND: The widespread acceptance of early surgery as a treatment for acute intertrochanteric fracture (ITF) has been accompanied by ongoing controversy due to conflicting conclusions presented in previous studies. This study aims to compare the occurrence of perioperative complications and mortality, as well as functional outcomes in older patients with ITF who underwent either early or delayed surgery. METHODS: A retrospective multicenter cohort study involving 7414 patients with ITF between Jan. 2017 and Dec. 2021 was conducted. After predefined participants selection inclusion and exclusion criteria, 2323 surgically treated ITF patients were included and analyzed utilizing propensity score matching (PSM) method. Their demographics, injury-related data, surgery-related data, and perioperative adverse outcomes during hospitalization were collected and compared between the early or delayed surgery groups by PSM with a 1:4 ratio. All participants received a minimum of two-year follow-up and perioperative outcomes, functional outcomes, and survival analyses were conducted and compared. RESULTS: After adjustment for potential confounders, there were no significant difference in surgery duration, intraoperative blood loss, transfusion rate, mortality rates, functional outcomes, and perioperative complications rates including severe complications, cardiac complications, pulmonary complications, and neurological complications regardless of whether the patient was treated with early or delayed surgery (all P > 0.05). Although length of hospital stay (mean, 11.5 versus 14.4 days, P < 0.001), total hospital costs (mean, 39305 versus 42048 yuan, P < 0.001), and minor complications rates including hematological complications (31.7% versus 41.2%, P = 0.007) and nutritional/metabolic complications (59.3% versus 66.4%, P = 0.039) were lower in the early surgery group, our result indicated patients with early surgery were more inclined to receive more blood transfusion (mean, 2.8 versus 2.2 units, P = 0.004). CONCLUSIONS: Our findings suggest that a 48-hour delay in surgical intervention for older patients with an ITF does not result in a higher mortality rate, worse functional outcomes, and increased incidence of major perioperative complications when compared to early surgery. While expedited surgery is undoubtedly necessary for suitable patients, a reasonable preoperative delay of 48 h may be justified and safe for those with severe conditions, rather than strictly adhering to the current guidelines.

Enhancing visual working memory in schizophrenia: effects of frontoparietal theta tACS in low-performing patients.

Schizophrenia is a complex neuro-psychiatric disorder including positive symptoms, negative symptoms, and cognitive deficits. A key cognitive dysfunction in schizophrenia is a deficit in visual working memory (VWM). VWM involves three distinct stages: encoding, maintenance, and retrieval. The deficit in any one stage would produce the same symptom (i.e., poor VWM), although their causes are not the same. In this study, we used a retro-cue VWM task that provides helpful cues at different stages: early in maintenance (early cue), late in maintenance (late cue), or during retrieval (retrieval cue). This modification would help "tag" or identify the cognitive stage(s) most responsible for impaired VWM performance in schizophrenia. Additionally, we took advantage of this tagging feature and applied 6 Hz transcranial alternating current stimulation (tACS) over the right dorsolateral prefrontal cortex (DLPFC) and right posterior parietal cortex (PPC)-which has previously been shown to enhance VWM in low-performing healthy individuals-to examine whether tACS would improve a specific stage or all stages of VWM processing in schizophrenia. We observed that cues significantly enhanced performance in low-performing patients, who benefited equally from early and late maintenance cues, but not from retrieval cues. These low-performers also responded well to theta tACS in their overall VWM performance as opposed to a specific VWM stage. No improvement effect was observed in high-performing patients for both retro cue and tACS. Together, our data suggest that 1) low-performing patients' VWM deficits likely stem from poor memory consolidation rather than retrieval, 2) right frontoparietal theta tACS can improve low-performing patients' VWM performance, and 3) such facilitatory tACS effect is not selective of a specific VWM stage and thus is likely driven by an improvement in overall visual attention.

Efficacy and safety of different drugs for the treatment of bacterial vaginosis: a systematic review and network meta-analysis.

Objective: Bacterial vaginosis is a disease caused by vaginal microecology disorder, which seriously affects female health. At present, there are many drugs to treat BV, and this study aims to compare the efficacy and safety of multiple drugs for BV through a network meta-analysis (NMA). Methods: All studies were sourced from PubMed and Embase databases from the establishment date to April 13, 2023. We evaluated the clinical cure success rate and adverse effects (abnormal increase in vaginal discharge, external genital irritation, and vulvar itching) and performed subgroup analyses of the clinical cure success rate for different modes of administration. All statistical analyses were performed using R and STATA 14.0 software for network meta-analysis. Results: We included 42 studies that met the criteria, involving a total of 8382 patients. Network meta-analysis results showed that metronidazole and secnidazole had a higher rate of adverse reactions than placebo (RR 7.06; 95%-CI 2.61-19.10, RR 4.03; 95%-CI 1.63-9.98), the adverse reaction rate of probiotics group was lower than that of metronidazole group (RR 0.44; 95%-CI 0.21-0.93). The clinical cure rate of oral ornidazole was better than clindamycin (RR 16.08; 95%-CI 1.72-150.47), Secnidazole (RR 8.17; 95%-CI 1.66-40.25) and probiotics. Direct meta-analysis results showed that ornidazole had a better clinical cure rate than Secnidazole (RR 1.22; 95%-CI 1.10-1.34), oral ornidazole had a better clinical cure rate than Secnidazole (RR 1.23; 95%-CI 1.11-1.36). The clinical cure rate of vaginal application of sucrose was better than metronidazole (RR 1.12; 95%-CI 1.03-1.21) and metronidazole had a lower clinical cure rate than probiotics (RR 0.68; 95%-CI 0.52-0.88). Conclusions: The results of this systematic review and network meta-analysis suggest that ornidazole may be an effective alternative for the treatment of BV, and that sucrose and probiotics are potential BV treatments that need to be validated by more high-quality clinical studies in the future.

Disrupting stroke-induced GAT-1-syntaxin1A interaction promotes functional recovery after stroke.

Although stroke is a frequent cause of permanent disability, our ability to promote stroke recovery is limited. Here, we design a small-molecule stroke recovery promoting agent that works by dissociating γ-aminobutyric acid (GABA) transporter 1 (GAT-1) from syntaxin1A (Synt1A), a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein. Stroke induces an increase in GAT-1-Synt1A interaction in the subacute phase, a critical period for functional recovery. Uncoupling GAT-1-Synt1A reverses stroke-induced GAT-1 dysfunction and cortical excitability decline and enhances synaptic GABAergic inhibition and consequently cortical oscillations and network plasticity by facilitating the assembly of the SNARE complex at the synapse. Based on the molecular mechanism of GAT-1 binding to Synt1A, we design GAT-1-Synt1A blockers. Among them, ZLQ-3 exhibits the greatest potency. Intranasal use of ZLQ-3-1, a glycosylation product of ZLQ-3, substantially lessens impairments of sensorimotor and cognitive functions in rodent models. This compound, or its analogs, may serve as a promoting agent for stroke recovery.

Altitude and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) in China: A Population-Based Study.

Yufei Wang, Qiong Meng, Jin Zhang, Bing Guo, Nanyan Li, Qian Deng, Julinling Hu, Deji Quzong, Han Guan, Danzhen Wangjiu, Hui Yu, Zhifeng Li, and Junmin Zhou. Altitude and metabolic dysfunction-associated fatty liver disease (MAFLD) in China: a population-based study. High Alt Med Biol. 00:00-00, 2024. Objectives: The epidemiological evidence for the relationship between altitude and metabolic dysfunction-associated fatty liver disease (MAFLD) is scarce. This study aims to examine the altitude-MAFLD relationship and explore the potential mediators explaining the relationship. Methods: Data were derived from the China Multi-Ethnic Cohort. The participants' altitude information was extracted from their residential addresses. MAFLD was diagnosed based on radiographically confirmed hepatic steatosis and any one of the following three items: overweight/obese status, diabetes mellitus, or metabolic dysregulation. We performed multivariable logistic regression and mediation analyses to assess the altitude-MAFLD associations and potential mediators, respectively. In the mediation analysis, mediation proportion is an estimate of the extent to which the total effect (altitude-MAFLD association) is accounted for by the pathway through the mediators. Results: In total, 87,679 participants (female: 60.7%, mean age: 51.36 years) were included. The odds ratio of MAFLD was 1.61 (95% confidence interval [CI]: 1.52-1.71) between high and low altitudes, 1.52 (95% CI: 1.43-1.62) between high and middle altitudes, and 1.06 (95% CI: 1.01-1.10) between middle and low altitudes. Of the total estimated effect between high and low altitude, physical activity and vegetable intake accounted for 15.7% (95% CI: 12.8-19.1) and 3.8% (95% CI: 1.2-6.6), respectively. Of the total estimated effect between high and middle altitude, physical activity and vegetable intake accounted for 31.4% (95% CI: 26.2-34.8) and 2.3% (95% CI: 0.6-3.8), respectively. Of the total estimated effect between middle and low altitude, vegetable intake accounted for 11.8% (95% CI: 3.2-61.5). Conclusion: Higher altitude was associated with increased odds of MAFLD, and physical activity and vegetable intake mediated such association. Multifaceted efforts should be taken in public health to promote healthy lifestyles among higher altitude residents.

A Critical Review of Phenomenological Research Related to Schizophrenia in China.

INTRODUCTION: Phenomenological qualitative research delves into the essence and meaning of phenomena through subjects' lived experiences. Despite its widespread use in humanities disciplines, its integration with psychopathology is rare in China. METHODS: We systematically reviewed phenomenological studies on schizophrenia in China to assess their content and quality and offer insights for future research. Following PRISMA guidelines, we reviewed 28 articles. Quality assessment focused on adherence to theoretical principles, transparency, coherence, and evidence. RESULTS: Topics covered various illness-related experiences, including treatment seeking, medication, hospitalization, rehabilitation, relapse, sexuality, and reproduction. Some studies also explored caregiver experiences. However, only 5 articles were rated excellent, with most lacking theoretical depth. CONCLUSION: Phenomenological research related to schizophrenia in China is mostly peripheral to the psychopathology of schizophrenia, and the qualification rate is low. Researchers should keep in mind the nature of phenomenological attitudes, delving into the essence and meaning of phenomena.

A lightweight defect detection algorithm for escalator steps.

In this paper, we propose an efficient target detection algorithm, ASF-Sim-YOLO, to address issues encountered in escalator step defect detection, such as an excessive number of parameters in the detection network model, poor adaptability, and difficulties in real-time processing of video streams. Firstly, to address the characteristics of escalator step defects, we designed the ASF-Sim-P2 structure to improve the detection accuracy of small targets, such as step defects. Additionally, we incorporated the SimAM (Similarity-based Attention Mechanism) by combining SimAM with SPPF (Spatial Pyramid Pooling-Fast) to enhance the model's ability to capture key information by assigning importance weights to each pixel. Furthermore, to address the challenge posed by the small size of step defects, we replaced the traditional CIoU (Complete-Intersection-over-Union) loss function with NWD (Normalized Wasserstein Distance), which alleviated the problem of defect missing. Finally, to meet the deployment requirements of mobile devices, we performed channel pruning on the model. The experimental results showed that the improved ASF-Sim-YOLO model achieved an average accuracy (mAP50) of 96.8% on the test data set, which was a 22.1% improvement in accuracy compared to the baseline model. Meanwhile, the computational complexity (in GFLOPS) of the model was reduced to a quarter of that of the baseline model, while the frame rate (FPS) was improved to 575.1. Compared with YOLOv3-tiny, YOLOv5s, YOLOv8s, Faster-RCNN, TOOD, RTMDET and other deep learning-based target recognition algorithms, ASF-Sim-YOLO has better detection accuracy and real-time processing capability. These results demonstrate that ASF-Sim-YOLO effectively balances lightweight design and performance improvement, making it highly suitable for real-time detection of step defects, which can meet the demands of escalator inspection operations.

Peak Identification in Evolutionary Multimodal Optimization: Model, Algorithms, and Metrics.

In this paper, we present a two-phase multimodal optimization model designed to efficiently and accurately identify multiple optima. The first phase employs a population-based search algorithm to locate potential optima, while the second phase introduces a novel peak identification (PI) procedure to filter out non-optimal solutions, ensuring that each identified solution represents a distinct optimum. This approach not only enhances the effectiveness of multimodal optimization but also addresses the issue of redundant solutions prevalent in existing algorithms. We propose two PI algorithms: HVPI, which uses a hill-valley approach to distinguish between optima, without requiring prior knowledge of niche radii; and HVPIC, which integrates HVPI with bisecting K-means clustering to reduce the number of fitness evaluations (FEs). The performance of these algorithms was evaluated using the F-measure, a comprehensive metric that accounts for both the accuracy and redundancy in the solution set. Extensive experiments on a suite of benchmark functions and engineering problems demonstrated that our proposed algorithms achieved a high precision and recall, significantly outperforming traditional methods.

Upcycling Waste Polyethylene Terephthalate to Produce Nitrogen-Doped Porous Carbon for Enhanced Capacitive Deionization.

Porous carbon with a high surface area and controllable pore size is needed for energy storage. It is still a significant challenge to produce porous carbon in an economical way. Nitrogen-doped porous carbon (N-PC) was prepared through carbonization of a mixture of waste PET-derived metal-organic frameworks (MOFs) and ammonium. The obtained N-PC exhibits a large surface area and controlled pore size. When utilized as an electrode material for supercapacitors, the N-PC exhibits a specific capacitance of 224 F g-1, significantly surpassing that of commercial activated carbon (AC), which has a capacitance of 111 F g-1. In the subsequent capacitive deionization (CDI) tests, the N-PC demonstrated a maximum salt adsorption capacity of 19.9 mg g-1 at 1.2 V in a NaCl electrolyte (0.5 g L-1), and the salt adsorption capacity increased to 24.7 mg g-1 at 1.4 V. The N-PC electrode also exhibited superior regeneration. The present work not only presents a potential approach to develop cost-effective electrodes for seawater purification but also paves the way for recycling of waste plastics into high value-added products.

Abalone shell-derived Mg-doped mesoporous hydroxyapatite microsphere drug delivery system loaded with icariin for inducing apoptosis of osteosarcoma cells.

Hydroxyapatite (HAP) porous microspheres with very high specific surface area and drug loading capacity, as well as excellent biocompatibility, have been widely used in tumour therapy. Mg2+ is considered to be a key factor in bone regeneration, acting as an active agent to stimulate bone and cartilage formation, and is effective in accelerating cell migration and promoting angiogenesis, which is essential for bone tissue repair, anti-cancer, and anti-infection. In this study, abalone shells from a variety of sources were used as raw materials, and Mg2+-doped abalone shell-derived mesoporous HAP microspheres (Mg-HAP) were prepared by hydrothermal synthesis as Mg2+/ icariin smart dual delivery system (ICA-Mg-HAP, IMHA). With increasing of Mg2+ doping, the surface morphology of HAP microspheres varied from collapsed macroporous to mesoporous to smooth and non-porous, which may be due to Mg2+ substitution or coordination in the HAP lattice. At 30% Mg2+ doping, the Mg-HAP microspheres showed a more homogeneous mesoporous morphology with a high specific surface area (186.06 m2/g). The IMHA microspheres showed high drug loading (7.69%) and encapsulation rate (83.29%), sustained Mg2+ release for more than 27 days, sustained and stable release of icariin for 60 hours, and good responsiveness to pH (pH 6.4 > pH 5.6). In addition, the IMHA delivery system stimulated the rapid proliferation of bone marrow mesenchymal stem cells and induced apoptosis in MG63 cells by blocking the G2 phase cycle of osteosarcoma cells and stimulating the high expression of apoptotic genes (Bcl-2, caspase-3, -8, -9). This suggests that the abalone shell-based IMHA may have potential applications in drug delivery and tumour therapy.

A novel fluorescent sensor for evaluating pH changes in organophosphorus pesticides-treated cells and C. elegans.

pH plays an important role in the evaluation of the healthy status in versatile circumstances. The fluctuation of pH could be affected by complex internal and external stimuli. Especially, the abnormal pH changes is a common characteristic of organophosphorus pesticides (OPs)-caused damage owing to the irreversible inhibition of acetylcholinesterase (AChE) activity. Therefore, the rapid and efficient detection of pH changes is of great significance for predicting the OPs poisoning in living system. However, quick and convenient detecting pH levels in living cells is still limited by the lack of effective chemical tools. Here, a novel fluorescent probe TH-1 based on ESIPT mechanism was synthesized, showing specific fluorescent effects in different pH solutions. Importantly, the AChE catalyzed the hydrolysis product of acetylthiocholine iodide (ATCh) and changed the pH of solution, which influence its fluorescent intensity. Moreover, the probe TH-1 was applied to detecting the pH levels in living cells and C. elegans, providing an efficient chemical sensor for revealing the potential mechanisms of OPs in physiological and pathological processes.

Anion-Substituted Hybrid Zinc Halides with Remarkable Dielectric Switches.

Thermo-responsive dielectric switching hybrid halides, displaying reversible dielectric bistability, have recently made them highly versatile and attractive for their structural tunability and rich functional properties. However, the substantial improvement of the dielectric switching operating range is limited near room temperature, and obtaining ultra-wide dielectric switching temperature region is a major challenge. Herein, a remarkable dielectric switching effect is reported with ultra-wide dielectric switching temperature region in a hybrid halide system, caused by dipolar orientational polarization ascribing order-disorder phase transitions. The new A2BX4 hybrid halide [C6H5(CH2)4NH3]2ZnBr4 (4PBA-ZnBr4) with an ultra-wide dielectric hysteresis loop of about 55 K near room temperature is designed successfully through halogen substitution. Meanwhile, structurally similar hybrid materials 4PBA-ZnI4 were designed as controls. More interestingly, the crystal structure, phase transition temperature (Tc), dielectric and semiconductor properties exhibit significant discrepancies as the halogen atoms vary from Br to I. This discovery provides an efficiently regulated anionic framework to construct hybrid halides with ultra-wide high dielectric switching and reliable cycling stability by assembling with various cations, making them potentially excellent candidates for highly responsive room temperature smart switches or transducer devices.

Ultrasensitive Single-Molecule Biosensor by Periodic Modulation of Magnetic Particle Motion.

Ultrasensitive detection of low-abundance biomarkers by modern single-molecule technologies is critical for better diagnosis of severe diseases, but inevitable nonspecific bindings often cause fluctuations in the single-molecule counting results. Here we present an approach to improve the specificity in a single-molecule immunoassay by translating molecular binding signals into periodic nanomotion of magnetic particles. The sandwiched immunoassay is modified by using a long linker to tether one antibody onto a gold-covered substrate and a magnetic particle with another antibody coated as the reporter. By actively oscillating the particles with alternating magnetic fields, we could reliably identify specific binding through intensity fluctuation in plasmonic images of single particles. As a proof of concept, we demonstrate the detection of IFN-γ at the femtomolar level by the digital counting of specifically bound molecules. This active strategy outperforms existing passive motion-based approaches in sensitivity and speed, paving the way for disease diagnosis with low-abundance biomarkers.

Systemic lupus erythematosus: pathogenesis and targeted therapy.

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by dysregulated immune responses and autoantibody production, which affects multiple organs and varies in clinical presentation and disease severity. The development of SLE is intricate, encompassing dysregulation within the immune system, a collapse of immunological tolerance, genetic susceptibilities to the disease, and a variety of environmental factors that can act as triggers. This review provides a comprehensive discussion of the pathogenesis and treatment strategies of SLE and focuses on the progress and status of traditional and emerging treatment strategies for SLE. Traditional treatment strategies for SLE have mainly employed non-specific approaches, including cytotoxic and immunosuppressive drugs, antimalarials, glucocorticoids, and NSAIDs. These strategies are effective in mitigating the effects of the disease, but they are not a complete cure and are often accompanied by adverse reactions. Emerging targeted therapeutic drugs, on the other hand, aim to control and treat SLE by targeting B and T cells, inhibiting their activation and function, as well as the abnormal activation of the immune system. A deeper understanding of the pathogenesis of SLE and the exploration of new targeted treatment strategies are essential to advance the treatment of this complex autoimmune disease.

Naked Gene Delivery Induces Autophagy for Effective Treatment of Acute Lung Injury in a Mouse Model.

Background: Acute lung injury (ALI) leads to diffuse pulmonary interstitial and alveolar edema, further developing into acute respiratory distress syndrome (ARDS). The present therapeutic approaches showed limited effects with poor clinical efficacy or severe side effects. This study aims to develop novel pharmaceutical agents to reduce lung damage with acceptable side effects for ALI. Methods: Naked gene delivery system based on epigallocatechin 3-gallate (EGCG) was synthesized to deliver plasmid expressing DNA damage regulated autophagy modulator 1 (DRAM1), designated as EGCG/DRAM1 (ED). ED was characterized by dynamic light scattering analysis and transmission electron microscope. The biodistribution of ED in mice was measured by an in vivo small animal imaging system. The therapeutic potentials of ED were evaluated in MLE12 cells and LPS-induced ALI mice. Results: Our results showed that ED was nearly spherical with a diameter of ~100 nm and increased the stability of DRAM1 plasmid that encapsulated. The synthesized ED showed negligible toxicity at the selected experimental concentration in MLE12 cells. ED could be taken up by MLE12 cells with high efficiency and escape from the lysosome. In ALI mice, ED facilitated the accumulation and retention of DRAM1 plasmid in lung, and attenuated pulmonary edema and pulmonary vascular permeability. The therapeutic effects of ED on ALI were associated with increased autophagy and reduced oxidative stress in lung. Conclusion: In summary, ED attenuated pulmonary edema and pulmonary vascular permeability, and improved pulmonary dysfunction in ALI mice. This naked gene delivery system for autophagy enhancement may serve as a potential therapeutic strategy to attenuate ALI.

Cutoff Values for Glycated Albumin, 1,5-Anhydroglucitol, and Fructosamine as Alternative Markers for Hyperglycemia.

BACKGROUND: Glycated albumin (GA), 1,5-anhydroglucitol (1,5-AG), and fructosamine have attracted considerable interest as markers of hyperglycemia. This study aimed to evaluate the optimal cutoff values for GA, 1,5-AG, and fructosamine and to determine their respective diagnostic efficacies in relation to hyperglycemia. METHODS: We enrolled 6012 individuals who had undergone fasting blood glucose (FBG) and Hemoglobin A1c (HbA1c) tests along with at least one alternative glycemic marker. Receiver operating characteristic (ROC) curves and the upper or lower limit of the reference range (97.5 or 2.5 percentiles) were used to ascertain the optimal cutoff values. Follow-up data from healthy individuals were used to identify patients who developed diabetes mellitus (DM). RESULTS: The ROC cutoff values for GA, 1,5-AG, and fructosamine were 13.9%, 13.3 µg/mL, and 278 µmol/L, respectively, with corresponding area under the curve (AUC) values of 0.860, 0.879, and 0.834. The upper limits of the reference intervals for GA and fructosamine were 15.1% and 279 µmol/L, respectively, and the lower limit for 1,5-AG was 5.3 µg/mL. Among the GA cutoff values, the ROC cutoff had the highest sensitivity. Analyzing the follow-up data showed that lowering the GA cutoff from 16.0% to 13.9% identified an additional 40 people with DM progression. CONCLUSIONS: Lowering the GA cutoff values significantly increased the sensitivity of DM diagnosis and enhanced its potential as a screening marker by identifying more individuals with diabetes progression. Conversely, modifications to the cutoff values for 1,5-AG and fructosamine did not confer any discernible diagnostic or predictive advantages.