Premorbid physical activity and prognosis after incident myocardial infarction: The atherosclerosis risk in communities study.

BACKGROUND: High to moderate levels of physical activity (PA) are associated with low risk of incident cardiovascular disease. However, it is unclear whether the benefits of PA in midlife extend to cardiovascular health following myocardial infarction (MI) in later life. METHODS: Among 1,111 Atherosclerosis Risk in Communities study participants with incident MI during Atherosclerosis Risk in Communities follow-up (mean age 73 [SD 9] years at MI, 54% men, 21% Black), PA on average 11.9 (SD 6.9) years prior to incident MI (premorbid PA) was evaluated as the average score of PA between visit 1 (1987-1989) and visit 3 (1993-1995) using a modified Baecke questionnaire. Total and domain-specific PA (sport, nonsport leisure, and work PA) was analyzed for associations with composite and individual outcomes of mortality, recurrent MI, and stroke after index MI using multivariable Cox models. RESULTS: During a median follow-up of 4.6 (IQI 1.0-10.5) years after incident MI, 823 participants (74%) developed a composite outcome. The 10-year cumulative incidence of the composite outcome was lower in the highest, as compared to the lowest tertile of premorbid total PA (56% vs. 70%, respectively). This association remained statistically significant even after adjusting for potential confounders (adjusted hazard ratio [aHR] 0.80 [0.67-0.96] for the highest vs. lowest tertile). For individual outcomes, high premorbid total PA was associated with a low risk of recurrent MI (corresponding aHR 0.64 [0.44, 0.93]). When domain-specific PA was analyzed, similar results were seen for sport and work PA. The association was strongest in the first year following MI (e.g., aHR of composite outcome 0.66 [95% CI 0.47, 0.91] for the highest vs. lowest tertile of total PA). CONCLUSIONS: Premorbid PA was associated positively with post-MI cardiovascular health. Our results demonstrate the additional prognostic advantages of PA beyond reducing the risk of incident MI.

Comamonas resistens sp. nov. and Pseudomonas triclosanedens sp. nov., two members of the phylum Pseudomonadota isolated from the wastewater treatment system of a pharmaceutical factory.

Five strains of two novel species were isolated from the wastewater treatment systems of a pharmaceutical factory located in Zhejiang province, PR China. Strains ZM22T and Y6 were identified as belonging to a potential novel species of the genus Comamonas, whereas strains ZM23T, ZM24 and ZM25 were identified as belonging to a novel species of the genus Pseudomonas. These strains were characterized by polyphasic approaches including 16S rRNA gene analysis, multi-locus sequence analysis, average nucleotide identity (ANI), in silico DNA-DNA hybridization (isDDH), physiological and biochemical tests, as well as chemotaxonomic analysis. Genome-based phylogenetic analysis further confirmed that strains ZM22T and Y6 form a distinct clade closely related to Comamonas testosteroni ATCC 11996T and Comamonas thiooxydans DSM 17888T. Strains ZM23T, ZM24 and ZM25 were grouped as a separate clade closely related to Pseudomonas nitroreducens DSM 14399T and Pseudomonas nicosulfuronedens LAM1902T. The orthoANI and isDDH results indicated that strains ZM22T and Y6 belong to the same species. In addition, genomic DNA fingerprinting demonstrated that these strains do not originate from a single clone. The same results were observed for strains ZM23T, ZM24 and ZM25. Strains ZM22T and Y6 were resistant to multiple antibiotics, whereas strains ZM23T, ZM24 and ZM25 were able to degrade an emerging pollutant, triclosan. The phylogenetic, physiological and biochemical characteristics, as well as chemotaxonomy, allowed these strains to be distinguished from their genus, and we therefore propose the names Comamonas resistens sp. nov. (type strain ZM22=MCCC 1K08496T=KCTC 82561T) and Pseudomonas triclosanedens sp. nov. (type strain ZM23T=MCCC 1K08497T=JCM 36056T), respectively.

The relationship between thiamin, folic acid and cognitive function in a rat model of uremia.

End-stage renal disease is a worldwide health burden, but the pathogenesis of uremia-associated cognitive impairment (CI) is poorly recognized. We hypothesized that uremia brings about deficiency of thiamin and folic acid and causes CI by inducing oxidative stress. Therefore, 24 Sprague-Dawley rats were randomly divided into two groups: a 5/6 nephrectomy group (n = 12) and a sham-operated group (n = 12). The Morris water maze was used to assess the cognitive function eight weeks post-surgery, and serum levels of thiamin, folic acid and homocysteine were detected subsequently. Brain and kidney tissues were collected for pathological examination and 8-Hydroxy-2'-deoxyguanosine (8-OHdG) immunochemistry staining. Results showed that the escape latency on training days 1-2 was longer, and the time in quadrant IV on experimental day 6 was significantly shorter in 5/6 nephrectomy group. Meanwhile, the uremic rats showed decreased thiamin, folic acid and increased homocysteine. We also found the time in quadrant IV was positively correlated with thiamin and folic acid level, while negatively correlated with the blood urea nitrogen and 8-OHdG positive cell proportion. Furthermore, in 5/6 nephrectomy group, the hippocampal neuron count was significantly reduced, and a greater proportion of 8-OHdG positive cells were detected. Pretreating LPS-stimulated rat microglial cells with thiamin or folic acid in vitro alleviated the inflammatory impairment in terms of cell viability and oxidative stress. In summary, we applied a uremic rat model and proved that uremia causes serum thiamin and folic acid deficiency, homocysteine elevation, along with neuron reduction and severe oxidative stress in hippocampus, finally leading to CI.

Fibrinogen-albumin ratio predicts treatment response in phospholipase A2 receptor-associated membranous nephropathy with nephrotic syndrome.

BACKGROUND: The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN. METHODS: 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman's correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission. RESULTS: In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766. CONCLUSIONS: FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.

High-Performance Four-Channel Tactile Sensor for Measuring the Magnitude and Orientation of Forces.

Flexible sensors have gained popularity in recent years. This study proposes a novel structure of a resistive four-channel tactile sensor capable of distinguishing the magnitude and direction of normal forces acting on its sensing surface. The sensor uses EcoflexTM00-30 as the substrate and EGaIn alloy as the conductive filler, featuring four mutually perpendicular and curved channels to enhance the sensor's dynamic responsiveness. Experiments and simulations show that the sensor has a large dynamic range (31.25-100 mΩ), high precision (deviation of repeated pressing below 0.1%), linearity (R2 above 0.97), fast response/recovery time (0.2 s/0.15 s), and robust stability (with fluctuations below 0.9%). This work uses an underactuated robotic hand equipped with a four-channel tactile sensor to grasp various objects. The sensor data collected effectively predicts the shapes of the objects grasped. Furthermore, the four-channel tactile sensor proposed in this work may be employed in smart wearables, medical diagnostics, and other industries.

Liver integrity and the risk of Alzheimer's disease and related dementias.

INTRODUCTION: We examined midlife (1990-1992, mean age 57) and late-life (2011-2013, mean age 75) nonalcoholic fatty liver disease (NAFLD) and aminotransferase with incident dementia risk through 2019 in the Atherosclerosis Risk in Communities (ARIC) Study. METHODS: We characterized NAFLD using the fatty liver index and fibrosis-4, and we categorized aminotransferase using the optimal equal-hazard ratio (HR) approach. We estimated HRs for incident dementia ascertained from multiple data sources. RESULTS: Adjusted for demographics, alcohol consumption, and kidney function, individuals with low, intermediate, and high liver fibrosis in midlife (HRs: 1.45, 1.40, and 2.25, respectively), but not at older age, had higher dementia risks than individuals without fatty liver. A U-shaped association was observed for alanine aminotransferase with dementia risk, which was more pronounced in late-life assessment. DISCUSSION: Our findings highlight dementia burden in high-prevalent NAFLD and the important feature of late-life aminotransaminase as a surrogate biomarker linking liver hypometabolism to dementia. Highlights Although evidence of liver involvement in dementia development has been documented in animal studies, the evidence in humans is limited. Midlife NAFLD raised dementia risk proportionate to severity. Late-life NAFLD was not associated with a high risk of dementia. Low alanine aminotransferase was associated with an elevated dementia risk, especially when measured in late life.

Who will name new plant species? Temporal change in the origins of taxonomists in China.

Discovery rates of new plant species need to be accelerated because many species will be extinct before they are formally described. Current studies have focused on where new species may occur and their characteristics. However, who will actually discover and describe these new species has received limited attention. Here, we used 31 576 vascular plant species distributed and described in China as a case study to explore the temporal patterns of the nationalities of the taxonomists. We found that most recently described species are endemic species, and there has been an increasing proportion of species descriptions by resident Chinese taxonomists over time. The proportion of species described by resident taxonomists reached an average of 80.8% between 1977 and 2018. By contrast, species discoveries by non-resident experts, often non-endemic species, showed signs of levelling off. Our study underscores an urgent need for training of, support for and collaboration with resident taxonomists in megadiverse countries with a high potential of discovering undescribed plant species.

Improving the performance of reference-frame-independent quantum key distribution with advantage distillation technology.

The reference-frame-independent quantum key distribution (RFI-QKD) has the advantage of tolerating reference frames that slowly vary. It can generate secure keys between two remote users with slowly drifted and unknown reference frames. However, the drift of reference frames may inevitably compromise the performance of QKD systems. In the paper, we employ the advantage distillation technology (ADT) to the RFI-QKD and the RFI measurement-device-independent QKD (RFI MDI-QKD), and we then analyze the effect of ADT on the performance of decoy-state RFI-QKD and RFI MDI-QKD in both asymptotic and nonasymptotic cases. The simulation results show that ADT can significantly improve the maximum transmission distance and the maximum tolerable background error rate. Furthermore, the performance of RFI-QKD and RFI MDI-QKD in terms of the secret key rate and maximum transmission distance are still greatly improved when statistical fluctuations are taken into account. Our work combines the merits of the ADT and RFI-QKD protocols, which further enhances the robustness and practicability of QKD systems.

Patterns of use of symptomatic treatments for Alzheimer's disease dementia (AD).

BACKGROUND: Symptomatic treatment for Alzheimer's disease (AD) dementia could temporarily slow symptom worsening and improve the quality of life for both AD dementia patients and their caregivers. A comprehensive evaluation of symptomatic treatment patterns using recent data for newly diagnosed AD dementia has not been performed and compared across different countries. METHODS: The drug name, time to the first therapy, duration, discontinuation or switches were described in newly diagnosed AD dementia patients in two databases (a major U.S. health plan [US] and UK-Clinical Practice Research Datalink [CPRD GOLD]). This analysis included patients with newly diagnosed AD dementia in 2018-2019, who initiated symptomatic AD drug therapy, with ≥ 1 year baseline period and ≥ 1 year of follow-up. RESULTS: Over median follow-ups of 698 and 645 days, 63% and 65% of AD dementia patients used symptomatic treatments, with 34% and 77% newly initiating therapy, constituting analytic samples of 7637 patients in the US database and 4470 patients in the CPRD, respectively. The median time to the first therapy was 14 days for US and 49 days for CPRD; donepezil ranked the as most frequently used (69% vs 61%), followed by memantine (19% vs 28%) in the US database and CPRD, respectively. Median time on first therapy was 213 and 334 days, and 30% and 12% of patients proceeded to a second treatment in the US and CPRD databases, respectively. CONCLUSION: Approximately two thirds of newly diagnosed AD dementia patients utilized approved symptomatic treatment. Time on first therapy was relatively short (< 1 year) and the majority did not move to a second therapy, highlighting the need for better adherence and persistence to existing AD symptomatic therapies and the need for additional therapies to alleviate the significant burden of AD dementia.

Qinggan Huoxue Recipe attenuates Alcoholic Liver Disease by suppressing PI3K/AKT signaling pathway based on network pharmacology.

Qinggan Huoxue Recipe (QGHXR) is originated from Xiao Chaihu Decotion. Many experimental studies have confirmed that QGHXR can significantly alleviate the symptoms of alcoholic liver disease (ALD), but the detailed mechanism is still unclear. Using traditional Chinese medicine network pharmacology analysis system database and animal experiments, we found that 180 potentially chemical compositions and 618 potential targets were screened from the prescription, which shared 133 signal pathways with ALD. Through animal experiments, it was found that QGHXR could reduce the liver total cholesterol (TC), serum TC, alanine aminotransferase, aspartate aminotransferase of ALD mice, reduce the lipid droplets and inflammatory injury of liver tissue. Meanwhile, it can also increase PTEN, decrease PI3K and AKT mRNA levels. In this study, we obtained the targets and pathways of QGHXR in the treatment of ALD, and preliminatively verified that QGHXR may improve ALD through PTEN/PI3K/AKT signaling pathway.

Tunable Sulfated Alginate-based Hydrogel Platform with enhanced anti-inflammatory and antioxidant capacity for promoting burn wound repair.

Amidst progressive advancements in tissue engineering, there has been a significant enhancement in the efficacy of anti-inflammatory hydrogel dressings, addressing a myriad of clinical challenges on wound healing. A frequent complication during the initial stages of deep second-degree burn wound healing is the onset of an inflammatory storm, typically occurring without effective intervention. This event disrupts normal biological healing sequences, leading to undesirable regression. In response, we have customized a tunable, multidimensional anti-inflammatory hydrogel platform based on sulfated alginates (Algs), loaded with Prussian blue (PB) nanozymes. This platform competently eliminates surplus reactive oxygen species (ROS) present in the wound bed. Algs, functioning as a mimic of sulfated glycosaminoglycans (including heparin, heparan sulfate, and chondroitin sulfate) in the extracellular matrices (ECM), demonstrate a high affinity towards inflammatory chemokines such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1). This affinity effectively impedes the infiltration of inflammatory cells into the wound. Concurrently, Algs markedly modulate the macrophage phenotype transition from M1 to M2. Ultimately, our potent anti-inflammatory hydrogels, which strategically target inflammatory chemokines, M1 macrophages, and ROS, successfully attenuate dysregulated hyperinflammation in wound sites. Precise immunomodulation administered to deep second-degree burn wounds in mice has demonstrated promotion of neovascular maturation, granulation tissue formation, collagen deposition, and wound closure. Our biomimetic hydrogels, therefore, represent a significant expansion in the repertoire of anti-inflammatory strategies available for clinical practice.

Analysis of Chemical Constituents of Chrysanthemum morifolium Extract and Its Effect on Postprandial Lipid Metabolism in Healthy Adults.

Chrysanthemum extract possesses antioxidant potential and carbohydrate and fat digestive enzyme inhibitory in vitro. However, no evidence supporting chrysanthemum in modulation of postprandial lipemia and antioxidant status in humans presently exists. This study was to analyze the composition of Imperial Chrysanthemum (IC) extract and determine the effect on changes in postprandial glycemic and lipemic response and antioxidant status in adults after consumption of a high-fat (HF) meal. UHPLC-MS method was used to analyze the components of two kinds of IC extracts (IC-P/IC-E) and in vitro antioxidant activities were evaluated using 1,1-diphenyl-2-picrylhydraxyl (DPPH), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and Hydroxyl radical (HR) radical scavenging assays. Following a randomized design, 37 healthy adults (age, 25.2 ± 2.6 years, and BMI, 20.9 ± 1.5 kg/m2) were assigned to two groups that consumed the HF meal, or HF meal supplemented by IC extract. Blood samples were collected at fasting state and then at 0.5, 1, 2, 4, 6 and 8 h after the meal consumption. There were 12 compounds with relative content of more than 1% of the extracts, of which amino acid and derivatives, flavonoids, carboxylic acids and derivatives were the main components. Compared with IC-E, the contents of flavonoids in IC-P increased significantly (p < 0.05), and the cynaroside content exceeded 30%. In addition, IC-P showed strong free radical scavenging activity against DPPH, ABTS and HR radicals. Furthermore, according to repeated−measures ANOVA, significant differences were observed in the maximal changes for postprandial glucose, TG, T-AOC and MDA among the two groups. Postprandial glucose has significant difference between the two groups at 1 h after meal and the level in IC group was significantly lower than that in control group. No significant differences were observed in the incremental area under the curve (iAUC) among the two groups. IC significantly improved the serum antioxidant status, as characterized by increased postprandial serum T-AOC, SOD, GSH and decreased MDA. This finding suggests that IC can be used as a natural ingredient for reducing postprandial lipemia and improving the antioxidant status after consuming a HF meal.

Proteome and physiological analyses reveal tobacco (Nicotiana tabacum) peroxidase 7 (POD 7) functions in responses to copper stress.

Copper is a micronutrient essential for plant growth and development. However, Cu is also a heavy metal element that has deleterious impacts on plants when excessively accumulated in the environment. To understand the molecular mechanism underlying tobacco in response to Cu stress, iTRAQ based technology was used to identify differentially expressed proteins (DEPs) and important metabolic pathways in tobacco plants treated with excessive CuSO4. The results showed that 180 DEPs were detected between the treatment and control, among which 78 were upregulated and 102 were downregulated. These DEPs can be functionally divided into 65 categories and are closely related to metabolic pathways, carbon metabolism, secondary metabolite biosynthesis, biosynthesis of antibiotics, glyoxylate and dicarboxylate metabolism, and glycolysis/gluconeogenesis. Peroxidase7 was significantly upregulated and was selected and overexpressed in tobacco. Then, positive transgenic lines and wild type plants were exposed to a Cu stress environment. The results showed that Peroxidase7 transgenic tobacco plants exhibited enhanced Cu stress resistance with decreased malondialdehyde and Cu contents, and increased shoot dry weight, root length, secondary root number, SOD, POD and CAT activity. The present study suggests that the ROS scavenging mechanism is essential for tobacco plants in response to Cu stress and that Peroxidase7 functions in tobacco plant resistance to excessive Cu environment.

Role of probiotics/synbiotic supplementation in glycemic control: A critical umbrella review of meta-analyses of randomized controlled trials.

The evidence regarding the beneficial effects of probiotics/synbiotic supplementation have been revealed by several meta-analyses, however some of these studies have fielded inconsistent results and a conclusion has yet to be reached. Therefore, the aim of present umbrella meta-analyses was to assess relevant evidence and elucidate the efficacy of probiotics/synbiotic supplementation in glycemic control. A comprehensive search in four databases (Cochrane library, PubMed, Web of science and Scopus) was performed to collect relevant studies up to August 2022, the pooled effects were measured with the use of random/fix-effect model depends on the heterogeneity. A total of 47 eligible meta-analyses involving 47,720 participants were identified to evaluate the pooled effects. The overall results showed that probiotics/synbiotic supplementation delivered significant decreases in fast plasma glucose (ES = -0.408, 95% CI: -0.518, -0.298; P < 0.001; I2 = 82.996, P < 0.001), fast plasma insulin (ES = -1.165, 95% CI: -1.454, -0.876; P < 0.001; I2 = 89.629, P < 0.001), homeostasis model assessment of insulin resistance (ES = -0.539, 95% CI: -0.624, -0.454; P < 0.001; I2 = 56.716, P < 0.001), and glycosylated hemoglobin (ES = -0.186, 95% CI: -0.270, -0.102; P < 0.001; I2 = 59.647, P = 0.001). Subgroup analysis showed that patients with impaired glucose homeostasis might benefit the most from probiotics/synbiotic supplementation. In conclusion, current umbrella meta-analysis strongly supporting the beneficial health effects of probiotics/synbiotic supplementation in glycemic control.

Effects of fish oil-derived n-3 polyunsaturated fatty acid on body composition, muscle strength and physical performance in older people: a secondary analysis of a randomised, double-blind, placebo-controlled trial.

BACKGROUND: the effects regarding n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on sarcopenia have been explored by several clinical trials. Nonetheless, the use of n-3 PUFA for improving body composition, muscle strength and physical performance in older people is conflicting. OBJECTIVES: our aim was to perform a randomised, double-blind, controlled trial to evaluate the effects of 6-month n-3 PUFA supplementation on body composition, muscle strength and physical performance in older Chinese people. METHODS: in this double-blind, placebo-controlled trial, 200 eligible subjects were randomly assigned to receive 4 g/day fish oil capsules (1.34 g eicosapentaenoic [EPA] + 1.07 docosahexaenoic [DHA]) or 4 g/day corn oil capsules (EPA + DHA <0.05 g) for 6 months. The primary outcomes were the changes of body composition, muscle strength (hand grip strength) and physical performance (Timed Up and Go time). Secondary outcomes were the changes in serum lipid profiles. RESULTS: compared with control group, fish oil-derived n-3 PUFA supplementation resulted in significant increases in thigh circumference (interaction time × group effect P < 0.001), total skeletal muscle mass (interaction time × group effect P < 0.001) and appendicular skeletal muscle mass (interaction time × group effect P < 0.001); the differences were still significant even after height correction. Muscle strength and physical performance including hand grip strength (interaction time × group effect P < 0.001) and Timed Up and Go time (interaction time × group effect P < 0.001) were also improved after a 6-month fish oil-derived n-3 PUFA intervention. In terms of serum lipid profiles, fish oil-derived n-3 PUFA supplementation could significantly reduce serum level of triglyceride (interaction time × group effect P = 0.012) and increase high density lipoprotein cholesterol (interaction time × group effect P < 0.001); while no significant improvement was found in serum concentrations of total cholesterol (interaction time × group effect P = 0.413) and low density lipoprotein cholesterol (interaction time × group effect P = 0.089). CONCLUSIONS: our present trial demonstrated that a 6-month fish oil-derived n-3 PUFA supplementation could beneficially affect the body composition, muscle strength, physical performance and serum lipid profiles in older people, which could be into considerations when making strategies aiming to the primary prevention of sarcopenia.

End-to-end diabetic retinopathy grading based on fundus fluorescein angiography images using deep learning.

PURPOSE: To develop and validate a deep learning system for diabetic retinopathy (DR) grading based on fundus fluorescein angiography (FFA) images. METHODS: A total of 11,214 FFA images from 705 patients were collected to form the internal dataset. Three convolutional neural networks, namely VGG16, RestNet50, and DenseNet, were trained using a nine-square grid input, and heat maps were generated. Subsequently, a comparison between human graders and the algorithm was performed. Lastly, the best model was tested on two external datasets (Xian dataset and Ningbo dataset). RESULTS: VGG16 performed the best, with a maximum accuracy of 94.17%, and had an AUC of 0.972, 0.922, and 0.994 for levels 1, 2, and 3, respectively. For Xian dataset, our model reached the accuracy of 82.47% and AUC of 0.910, 0.888, and 0.976 for levels 1, 2, and 3. As for Ningbo dataset, the network performed with the accuracy of 88.89% and AUC of 0.972, 0.756, and 0.945 for levels 1, 2, and 3. CONCLUSIONS: A deep learning system for DR staging was trained based on FFA images and evaluated through human-machine comparisons as well as external dataset testing. The proposed system will help clinical practitioners to diagnose and treat DR patients, and lay a foundation for future applications of other ophthalmic or general diseases.

Tocotrienol-Rich Fractions Offer Potential to Suppress Pulmonary Fibrosis Progression.

Although pulmonary fibrosis (PF) is considered a rare disease, the incidence thereof has increased steadily in recent years, while a safe and effective cure remains beyond reach. In this study, the potential of tocotrienol-rich fractions (TRF) and carotene to alleviate PF was explored. PF was induced in Sprague-Dawley rats via a single intratracheal bleomycin (BLM) (5 mg/kg) instillation. These rats were subsequently treated with TRF, carotene, pirfenidone (Pir) and nintedanib (Nin) for 28 days via gavage administration, whereafter histopathological performance, biochemical functions and molecular alterations were studied in the lung tissues. Our results showed that TRF, carotene, Nin and Pir all ameliorated PF by reducing inflammation and resisting oxidative stress to varying degrees. The related mechanisms involved the TGF-ß1/Smad, PI3K/Akt and NF-κB signaling pathways. Ultimately, our findings revealed that, when combined with TRF, the therapeutic effects of Nin and Pir on PF were enhanced, indicating that TRF may, indeed, provide promising potential for use in combination therapy in the treatment of PF.

Security Analysis of Sending or Not-Sending Twin-Field Quantum Key Distribution with Weak Randomness.

Sending-or-not sending twin-field quantum key distribution (SNS TF-QKD) has the advantage of tolerating large amounts of misalignment errors, and its key rate can exceed the linear bound of repeaterless quantum key distribution. However, the weak randomness in a practical QKD system may lower the secret key rate and limit its achievable communication distance, thus compromising its performance. In this paper, we analyze the effects of the weak randomness on the SNS TF-QKD. The numerical simulation shows that SNS TF-QKD can still have an excellent performance under the weak random condition: the secret key rate can exceed the PLOB boundary and achieve long transmission distances. Furthermore, our simulation results also show that SNS TF-QKD is more robust to the weak randomness loopholes than the BB84 protocol and the measurement-device-independent QKD (MDI-QKD). Our results emphasize that keeping the randomness of the states is significant to the protection of state preparation devices.

Phase-Matching Quantum Key Distribution with Discrete Phase Randomization.

The twin-field quantum key distribution (TF-QKD) protocol and its variations have been proposed to overcome the linear Pirandola-Laurenza-Ottaviani-Banchi (PLOB) bound. One variation called phase-matching QKD (PM-QKD) protocol employs discrete phase randomization and the phase post-compensation technique to improve the key rate quadratically. However, the discrete phase randomization opens a loophole to threaten the actual security. In this paper, we first introduce the unambiguous state discrimination (USD) measurement and the photon-number-splitting (PNS) attack against PM-QKD with imperfect phase randomization. Then, we prove the rigorous security of decoy state PM-QKD with discrete phase randomization. Simulation results show that, considering the intrinsic bit error rate and sifting factor, there is an optimal discrete phase randomization value to guarantee security and performance. Furthermore, as the number of discrete phase randomization increases, the key rate of adopting vacuum and one decoy state approaches infinite decoy states, the key rate between discrete phase randomization and continuous phase randomization is almost the same.

Sending or Not-Sending Twin-Field Quantum Key Distribution with Flawed and Leaky Sources.

Twin-field quantum key distribution (TF-QKD) has attracted considerable attention and developed rapidly due to its ability to surpass the fundamental rate-distance limit of QKD. However, the device imperfections may compromise its practical implementations. The goal of this paper is to make it robust against the state preparation flaws (SPFs) and side channels at the light source. We adopt the sending or not-sending (SNS) TF-QKD protocol to accommodate the SPFs and multiple optical modes in the emitted states. We analyze that the flaws of the phase modulation can be overcome by regarding the deviation of the phase as phase noise and eliminating it with the post-selection of phase. To overcome the side channels, we extend the generalized loss-tolerant (GLT) method to the four-intensity decoy-state SNS protocol. Remarkably, by decomposing of the two-mode single-photon states, the phase error rate can be estimated with only four parameters. The practical security of the SNS protocol with flawed and leaky source can be guaranteed. Our results might constitute a crucial step towards guaranteeing the practical implementation of the SNS protocol.