Comprehensive evaluation of immune dysregulation in secondary hemophagocytic lymphohistiocytosis.

Host immune dysfunction plays a crucial role in the onset, progression, and outcome of hemophagocytic lymphohistiocytosis (HLH). This study aimed to comprehensively evaluate the peripheral immune profiles in patients with newly diagnosed secondary hemophagocytic lymphohistiocytosis (sHLH), and explore their predictive value for patient prognosis. A total of 77 patients with sHLH were enrolled in this study, with 31 of them experiencing mortality. Flow cytometry was used to assess the percentages, absolute numbers, and phenotypes of lymphocyte subsets. Simultaneously, cytokine levels and routine laboratory indicators were also collected. In sHLH patients, lymphocyte subset absolute numbers were significantly impaired, accompanied by T cell hyperactivation, B cell hyperactivation, and increased plasmablast proliferation. Prognostic analysis revealed that lower CD8+ T cell percentages, elevated APTT, IL-6, IL-10 levels, and increased CD4+CD28null T cell proportions were associated with poor patient outcomes. The study demonstrates dysregulation in the counts and phenotypes of lymphocyte subsets in sHLH patients. Several key factors, including IL-6, IL-10, APTT, and various T cell percentages, have potential as prognostic markers and therapeutic targets in sHLH.

Serum and urine metabolomics based on UPLC-QTOF/MS reveal the effect and potential mechanism of "schisandra-evodia" herb pair in the treatment of Alzheimer's disease.

The "schisandra-evodia" herb pair (S-E) is a herbal preparation to treat Alzheimer's disease (AD). This study aims to investigate the therapeutic efficacy and potential mechanism of S-E in AD rats, utilizing pharmacodynamic assessments and serum- and urine-based metabolomic analyses. Pharmacodynamic assessments included Morris water maze test, hematoxylin-eosin staining and immunohistochemistry experiments. The results of the study showed that the AD model was successful; the S-E significantly enhanced long-term memory and spatial learning in AD rats. Meanwhile, S-E notably ameliorated Aß25-35-induced cognitive impairment, improved hippocampal neuron morphology, decreased Aß deposition in the hippocampus and mitigated inflammatory damage. We then analyzed serum and urine samples using UPLC-MS/MS to identify potential biomarkers and metabolic pathways. Metabolomic analysis revealed alterations in 40 serum metabolites and 38 urine metabolites following S-E treatment, predominantly affecting pathways related to taurine and hypotaurine metabolism, linoleic acid metabolism, α-linolenic acid metabolism, glycerophospholipid metabolism and arachidonic acid metabolism. This study elucidates the biochemical mechanism underlying AD and the metabolic pathway influenced by S-E, laying the groundwork for future clinical applications.

Effects of Exercise Habits and Gender on Sports e-Learning Behavior: Evidence from an Eye-Tracking Study.

Background/Objective: In the post-epidemic era, an increasing number of individuals were accustomed to learning sports and physical activity knowledge online for fitness and health demands. However, most previous studies have examined the influence of e-learning materials and resources on learners and have neglected intrinsic factors such as experience and physiological characteristics. Therefore, we conducted a study to investigate the effect of exercise habits and gender on sports e-learning behavior via eye-tracking technology. Methods: We recruited a sample of 60 undergraduate students (mean age = 19.6) from a university in Nanjing, China. They were randomly assigned into 4 groups based on 2 genders × 2 exercise habits. Their gaze behavior was collected by an eye-tracking device during the experiment. The cognitive Load Test and Learning Effect Test were conducted at the end of the individual experiment. Results: (1) Compared to the non-exercise habit group, the exercise habit group had a higher fixation count (P<0.05), a shorter average fixation duration (P<0.05), a smaller average pupil diameter (P<0.05), and a lower subjective cognitive load (P<0.05) and better learning outcome (P<0.05). (2) Male participants showed a greater tendency to process information from the video area of interest (AOIs), and had lower subjective cognitive load (P < 0.05) and better learning outcomes (P < 0.05). (3) There was no interaction effect between exercise habits and gender for any of the indicators (P > 0.05). Conclusion: Our results indicate that exercise habits effectively enhance sports e-learning outcomes and reduce cognitive load. The exercise habits group showed significant improvements in fixation counts, average fixation duration, and average pupil diameter. Furthermore, male subjects exhibited superior learning outcomes, experienced lower cognitive load, and demonstrated greater attentiveness to dynamic visual information. These conclusions are expected to improve sports e-learning success and address educational inequality.

BadCM: Invisible Backdoor Attack Against Cross-Modal Learning.

Despite remarkable successes in unimodal learning tasks, backdoor attacks against cross-modal learning are still underexplored due to the limited generalization and inferior stealthiness when involving multiple modalities. Notably, since works in this area mainly inherit ideas from unimodal visual attacks, they struggle with dealing with diverse cross-modal attack circumstances and manipulating imperceptible trigger samples, which hinders their practicability in real-world applications. In this paper, we introduce a novel bilateral backdoor to fill in the missing pieces of the puzzle in the cross-modal backdoor and propose a generalized invisible backdoor framework against cross-modal learning (BadCM). Specifically, a cross-modal mining scheme is developed to capture the modality-invariant components as target poisoning areas, where well-designed trigger patterns injected into these regions can be efficiently recognized by the victim models. This strategy is adapted to different image-text cross-modal models, making our framework available to various attack scenarios. Furthermore, for generating poisoned samples of high stealthiness, we conceive modality-specific generators for visual and linguistic modalities that facilitate hiding explicit trigger patterns in modality-invariant regions. To the best of our knowledge, BadCM is the first invisible backdoor method deliberately designed for diverse cross-modal attacks within one unified framework. Comprehensive experimental evaluations on two typical applications, i.e., cross-modal retrieval and VQA, demonstrate the effectiveness and generalization of our method under multiple kinds of attack scenarios. Moreover, we show that BadCM can robustly evade existing backdoor defenses. Our code is available at https://github.com/xandery-geek/BadCM.

Novel multiclass classification machine learning approach for the early-stage classification of systemic autoimmune rheumatic diseases.

OBJECTIVE: Systemic autoimmune rheumatic diseases (SARDs) encompass a diverse group of complex conditions with overlapping clinical features, making accurate diagnosis challenging. This study aims to develop a multiclass machine learning (ML) model for early-stage SARDs classification using accessible laboratory indicators. METHODS: A total of 925 SARDs patients were included, categorised into SLE, Sjögren's syndrome (SS) and inflammatory myositis (IM). Clinical characteristics and laboratory markers were collected and nine key indicators, including anti-dsDNA, anti-SS-A60, anti-Sm/nRNP, antichromatin, anti-dsDNA (indirect immunofluorescence assay), haemoglobin (Hb), platelet, neutrophil percentage and cytoplasmic patterns (AC-19, AC-20), were selected for model building. Various ML algorithms were used to construct a tripartite classification ML model. RESULTS: Patients were divided into two cohorts, cohort 1 was used to construct a tripartite classification model. Among models assessed, the random forest (RF) model demonstrated superior performance in distinguishing SLE, IM and SS (with area under curve=0.953, 0.903 and 0.836; accuracy= 0.892, 0.869 and 0.857; sensitivity= 0.890, 0.868 and 0.795; specificity= 0.910, 0.836 and 0.748; positive predictive value=0.922, 0.727 and 0.663; and negative predictive value= 0.854, 0.915 and 0.879). The RF model excelled in classifying SLE (precision=0.930, recall=0.985, F1 score=0.957). For IM and SS, RF model outcomes were (precision=0.793, 0.950; recall=0.920, 0.679; F1 score=0.852, 0.792). Cohort 2 served as an external validation set, achieving an overall accuracy of 87.3%. Individual classification performances for SLE, SS and IM were excellent, with precision, recall and F1 scores specified. SHAP analysis highlighted significant contributions from antibody profiles. CONCLUSION: This pioneering multiclass ML model, using basic laboratory indicators, enhances clinical feasibility and demonstrates promising potential for SARDs classification. The collaboration of clinical expertise and ML offers a nuanced approach to SARDs classification, with potential for enhanced patient care.

A Novel Ultrafiltrate Extract of Propolis Exerts Anti-inflammatory Activity through Metabolic Rewiring.

Thousands of years ago, humans started to use propolis because of its medicinal properties, and modern science has successfully identified several bioactive molecules within this resinous bee product. However, a natural propolis extract which has been removed the adhesive glue and preserved propolis bioactive compounds is urgently needed to maximise the therapeutic opportunities. In this study, a novel ultrafiltrate fraction from Brazilian green propolis, termed P30K, was demonstrated with anti-inflammatory properties, both in vitro and in vivo. Total flavonoids and total phenolic acids content in P30K were 244.6 mg/g and 275.8 mg/g respectively, while the IC50 value of inhibition of cyclooxygenase-2 (COX-2) was 8.30 µg/mL. The anti-inflammatory activity of P30K was furtherly corroborated in experimental models of lipopolysaccharides (LPS)-induced acute liver and lung injury. Mechanistically, integrated GC-MS and LC-MS based serum metabolomics analysis revealed that P30K modulated citrate cycle (TCA), pyruvate, glyoxylate and dicarboxylate metabolism pathways to inhibit secretion of pro-inflammatory cytokines. Results of network pharmacology and molecular docking suggested that P30K targeted catechol-O-methyltransferases (COMT), 11ß-hydroxysteroid dehydrogenases (HSD11B1), and monoamine oxidases (MAOA and MAOB) to promote cellular metabolomic rewiring. Collectively, our work reveals P30K as an efficient therapeutic agent against inflammatory conditions and its efficacy is related to metabolic rewiring.

MicroRNA-148a-3p suppresses the glycolysis and Cell proliferation by targeting transmembrane protein 54 in liver cancer.

Liver cancer is the fourth most lethal cancer, but the treatment options for liver cancer are usually limited. Metabolic reprogramming is a hallmark of malignancy, ensuring activated cell glycolysis and increased macromolecular precursors required for the proliferation and migration of exuberant cancer cells. MicroRNAs (miRNAs) have been reported to participate in cancer metabolic shifts mainly by directly silencing the expression of specific genes. Here, we identified miR-148a-3p as a negative regulator for glycometabolism and cell proliferation in liver cancer. miR-148a-3p directly targets the 3'UTR of transmembrane protein 54 (TMEM54), leading to the significant inhibition of lactate production, glucose consumption, intracellular ATP level and extracellular acidification rate (ECAR), as well as the repression of the proliferation and colony formation ability of liver cancer cells. miR-148a-3p expression is often down-regulated in liver cancer tissues. In addition, there was a negative correlation between the expression levels of miR-148a-3p and TMEM54 in liver cancer tissues. Moreover, the low miR-148a-3p expression levels or high TMEM54 expression levels were associated with poorer prognosis in hepatocellular carcinoma (HCC) patients. Together, these findings support that the miR-148a-3p/TMEM54 regulatory pathway regulates the glycometabolism and cell proliferation in liver cancer, which is a possible target for the diagnosis and treatment of liver cancer.

Bioequivalence and Safety Assessment of 2 Formulations of Low-Dose Metformin Hydrochloride under Fasting Conditions in Healthy Chinese Participants: A Randomized Phase 1 Clinical Trial.

The incidence of type 2 diabetes is high, and the existing metformin hydrochloride (MH) tablets of 250 mg cannot meet the demands of the Chinese drug market. This study aimed to evaluate the bioequivalence and safety of generic formulations of MH tablets (test formulation [T], 250 mg/tablet) and innovative products (reference formulation [R], 250 mg/tablet) under fasting conditions. This was an open-label, single-dose, 2-period, 2-sequence crossover, single-center, randomized phase I clinical trial. T and R were considered bioequivalent if the adjusted geometric mean ratios (GMRs) and 90% confidence intervals of the area under the curve (AUC) and maximum concentration (Cmax ) were within the range of 0.8-1.25. Thirty-five participants completed the trial. The T/R adjusted GMRs (95.7% for Cmax , 98.7% for AUC0→t , 98.8% for AUC0→∞ ) were within the acceptable bioequivalence range of 80%-125%. No serious adverse events or suspected or unexpected serious adverse reactions occurred during this trial. The study findings confirmed that generic MH is a well-tolerated and bioequivalent alternative to innovative products under fasting conditions in healthy Chinese participants. (www.chinadrugtrials.org.cn; registration no. CTR20190356).

Knowledge Structure and Emerging Trends of Mild Cognitive Impairment with Dyssomnias in Recent 20 Years: A Bibliometric Analysis via CiteSpace and VOSviewer.

Background: Mild cognitive impairment (MCI), an intermediate stage between normal aging and dementia, has emerged as a prominent research area in geriatric care due to its heightened propensity for progressing toward dementia. Sleep plays a pivotal role in cognitive function, with dyssomnias not only exacerbating cognitive and affective symptoms associated with neurodegenerative diseases but also contributing to disease progression. Aim: This bibliometric analysis investigates the global research on MCI with dyssomnias over the past two decades, aiming to discern key findings, research domains, and emerging trends in this field. Methods: In this study, a bibliometric analysis was conducted using the search terms "MCI" and "sleep". Data were extracted from the Web of Science Core Collection database, and visualization and collaborative analysis were performed using CiteSpace and VOSviewer. Results: This study encompassed 546 publications from 2003 to 2023. The publication volume and citation rate consistently increased over time. Neurosciences, Clinical Neurology, and Geriatrics Gerontology emerged as the top three research fields. The Journal of Alzheimer's Disease had the highest publication count, while Sleep Medicine received the most citations. USA, China, and Italy led in publication output. Collaborative clusters among authors and institutions were identified, but cooperation between clusters was limited. Active cocited reference clusters included "obstructive sleep apnea", "possible mediating pathways", and "isolated rapid eye movement sleep behaviour disorder". The top frequently mentioned keywords, besides "MCI", were "Alzheimer's disease", "dementia", "risk factor", and "Parkinson's Disease". Notable keyword clusters spanned circadian rhythm, Parkinson's disease, MCI, dementia with Lewy body, subjective cognitive impairment, Lewy body disease, Alzheimer's disease, and dietary patterns. Conclusion: The field of MCI with dyssomnias is rapidly expanding, encompassing a wide range of neurodegenerative disorders and sleep disturbances. Current research endeavors are primarily focused on elucidating the underlying pathogenesis, predicting disease progression, and developing innovative treatment strategies for individuals affected by MCI with dyssomnias.

The impact of public leadership on collaborative administration and public health delivery.

BACKGROUND: This research depicts the linkage of public leadership on public health delivery (PHD) and collaborative administration. The research is also focused to examine the effect of public leadership on public health delivery through the intervening variable of collaborative administration by using both social information processing theory and collaboration theory. METHODS: This research is based on quantitative method. Data was collected from 464 public hospital administration in the context of Pakistan. This study evaluated data using SPSS, AMOS, and PROCESS Macro. RESULTS: Public leadership has a positive profound effect on public health delivery and collaborative administration, and that collaborative administration significantly promotes public health delivery. The outcomes also exposed that public leadership has substantial influence on public health delivery through intervening collaborative administration. CONCLUSIONS: Whilst public leadership demonstrated positive outcomes on public health delivery and collaborative administration, there is a need for more rigor studies on collaborative governance leadership, collaborative ethics and collaborative norms in the public health service.

Analysis on Application and Funding Situation of General，Young Scholar and Regional Scholar Programs from NSFC in Field of Integrated Traditional Chinese and Western Medicine in 2023 / 中国实验方剂学杂志

By combing the application and funding situation of general， young scholar and regional scholar programs from National Natural Science Foundation of China（NSFC） in field of integrated traditional Chinese and western medicine in 2023， this paper summarizes the distribution of supporting units， application and funding hotspots， and the problems of application and funding projects in this discipline， in order to provide a reference for applicants and supporting organizations to understand the hotspot dynamics and reporting requirements of the discipline. In 2023， the discipline of integrated traditional Chinese and western medicine received a total of 2 793 applications， and there were 1 254 applications for general programs， 1 278 applications for young scholar programs， and 261 applications for regional scholar programs. The amounts of project funding obtained by the three were 145， 164 and 35， respectively， and the funding rates were 11.56%， 12.83% and 13.41% in that order. From the situation of obtaining funding， the age distribution of the project leaders who obtained funding for the general， young scholar and regional scholar programs were mainly distributed in the age of 40-46， 30-34， 38-44 years， respectively. Within the supported programs， the Chinese medicine affiliations accounted for 55.52%. With respect to research subjects， the proportion of one single Chinese herbs， or monomers， or extracts accounted for 29.4%， but the proportion of Chinese herb pairs or prescriptions accounted for 47.1%. Research hotspots included ferroptosis， bile acid metabolism， macrophages， mitochondria， microglia， exosomes， intestinal flora， microecology and so on. The current research mainly focused on the common key problems of the advantageous diseases of Chinese and western integrative medicine， but still need to be improved in the basic theories of Chinese and western medicine and multidisciplinary cross-disciplinary research.

Harnessing the High Interfacial Electric Fields on Water Microdroplets to Accelerate Menshutkin Reactions.

Even though it is still an emerging field, the application of a high external electric field (EEF) as a green and efficient catalyst in synthetic chemistry has recently received significant attention for the ability to deliver remarkable control of reaction selectivity and acceleration of reaction rates. Here, we extend the application of the EEF to Menshutkin reactions by taking advantage of the spontaneous high electric field at the air-water interfaces of sprayed water microdroplets. Experimentally, a series of Menshutkin reactions were accelerated by 7 orders of magnitude. Theoretically, both density functional theory calculations and ab initio molecular dynamics simulations predict that the reaction barrier decreases significantly in the presence of oriented external electric fields, thereby supporting the notion that the electric fields in the water droplets are responsible for the catalysis. In addition, the ordered solvent and reactant molecules oriented by the electric field alleviate the steric effect of solvents and increase the successful collision rates, thus facilitating faster nucleophilic attack. The success of Menshutkin reactions in this study showcases the great potential of microdroplet chemistry for green synthesis.

Protective effect and mechanism of different proportions of "Danggui-Kushen" herb pair on ischemic heart disease.

This study aims to investigate the protective effect and mechanism of "Danggui-Kushen" herb pair (DKHP) on ischemic heart disease (IHD). The rat model of myocardial reperfusion injury (MIRI) was established by ligation of the left anterior descending coronary artery. Rats were randomly divided into seven groups and administered orally for 7 days: control group, IHD group, DKHP1:1 group, DKHP1:2 group, DKHP2:1 group, DKHP1:3 group, DKHP3:1 group, the dosage was 2.7 g/kg. Measure electrocardiogram (ECG), myocardial infarction and injury assessment, Hematoxylin and eosin (HE) staining to evaluate myocardial injury and the protective effect of DKHP. Lactate dehydrogenase (LDH), Reactive oxygen species (ROS), IL-1ß and IL-6 kit detection, immunohistochemical analysis, establishment of H9c2 cardiomyocyte hypoxia (Hypoxia) model, DKHP pretreatment for 3 h, MTT method to detect cell survival rate, cell immunofluorescence to observe NF- The expression of TLR-4, NF-κB, p-NF-κB, IKßα, p-IKßα, HIF-1α, VEGF and other genes and proteins were detected by κB nuclear translocation, mitochondrial membrane potential measurement, Western blot and Polymerase Chain Reaction (PCR). Compared with the model group, DKHP can reduce the size of myocardial infarction, reduce the levels of factors such as LDH, ROS, IL-1ß and IL-6, and improve the cell survival rate; Compared with the model group, DKHP can inhibit the nuclear transfer of NF-κB and reduce mitochondrial damage; the results of immunohistochemical analysis, PCR and Western blot showed that compared with the model group, DKHP can reduce TLR-4, p-NF-κB, Expression levels of p-IKßα, HIF-1α, VEGF and other proteins. Reveal that DKHP may play a protective role in ischemic heart disease by reducing inflammation and oxidative stress damage. DKHP may have protective effect on ischemic heart disease, and its mechanism may be through reducing inflammatory response and oxidative stress damage to achieve this protective effect.

The study of therapeutic efficacy and mechanisms of Schisandra chinensis and Evodia rutaecarpa combined treatment in a rat model of Alzheimer's disease.

Schisandra chinensis and Evodia rutaecarpa are traditional Chinese herbs used to treat neurodegenerative diseases. This study investigates the combined effects of SC and ER on learning and memory in an Alzheimer's disease rat model and their underlying mechanisms. Methods: High-performance liquid chromatography was employed to analyze the primary active constituents of Schisandra and Evodia. The effects of the combined treatment of Schisandra and Evodia on learning and memory in an Alzheimer's disease rat model were evaluated through Morris water maze and Hematoxylin-Eosin staining experiments. Immunohistochemical analysis was conducted to investigate the impact of S-E on Aß1-42 and P-tau proteins. Western blotting and real-time quantitative polymerase chain reaction were utilized to quantify the expression of pivotal proteins and genes within the BDNF/TRKB/CREB and GSK-3ß/Tau pathways. Results: The treatment group exhibited significant neuroprotective effects, ameliorating learning and memory impairments in the Alzheimer's disease rat model. The treatment regimen modulated the activity of the BDNF/TRKB/CREB and GSK-3ß/Tau pathways by influencing the expression of relevant genes, thereby reducing the generation of Aß1-42 and P-Tau proteins and inhibiting the deposition of senile plaques. Furthermore, among the three treatment groups, the combined treatment demonstrated notably superior therapeutic effects on Alzheimer's disease compared to the single-drug treatment groups.

High Electric Fields on Water Microdroplets Catalyze Spontaneous and Fast Reactions in Halogen-Bond Complexes.

The use of external electric fields as green and efficient catalysts in synthetic chemistry has recently received significant attention for their ability to deliver remarkable control of reaction selectivity and acceleration of reaction rates. Technically, methods of generating high electric fields in the range of 1-10 V/nm are limited, as in-vacuo techniques have obvious scalability issues. The spontaneous high fields at various interfaces promise to solve this problem. In this study, we take advantage of the spontaneous high electric field at the air-water interface of sprayed water microdroplets in the reactions of several halogen bond systems: Nu:--X-X, where Nu: is pyridine or quinuclidine and X is bromine or iodine. The field facilitates ultrafast electron transfer from Nu:, yielding a Nu-X covalent bond and causing the X-X bond to cleave. This reaction occurs in microseconds in microdroplets but takes days to weeks in bulk solution. Density functional theory calculations predict that the reaction becomes barrier-free in the presence of oriented external electric fields, supporting the notion that the electric fields in the water droplets are responsible for the catalysis. We anticipate that microdroplet chemistry will be an avenue rich in opportunities in the reactions facilitated by high electric fields and provides an alternative way to tackle the scalability problem.

Effects of nitrogen reduction combined with bio-organic fertilizer on soil bacterial community diversity of red raspberry orchard.

Understanding soil bacterial diversity under nitrogen reduction is necessary for the crucial role in soil nitrogen cycling. However, the effects of combined fertilization on soil chemical properties, microbial community structure, and yield are unknown. This study was conducted to investigate the effect of nitrogen fertilizer reduction with bio-organic fertilizer on soil bacterial community diversity of red raspberry orchard. Six treatments were set in this study: NF-100%, NF-75%, NF-50%, NF-25% and CF, no nitrogen fertilizer and bio-organic fertilizer for CK. The bacterial community structures of soil were analyzed by 16S rRNA gene amplification high-throughput sequencing technology. Nitrogen fertilizer reduction with bio-organic fertilizer increased soil organic matter (SOM), total nitrogen (TN), alkali-hydrolyzable nitrogen (AN), available phosphorus (AP), available potassium (AK), and reduced soil pH. NF-50% and NF-25% treatments increased the yield of red raspberry. Nitrogen reduction combined with bio-organic fertilizer increased the relative abundance of copiotrophic bacteria and decreased the relative abundance of oligotrophic bacteria. The increase in copiotrophic bacteria in the soil of red raspberry orchard could indicate an increase in soil nutrient availability, which have positive implications for soil fertility and production. However, nitrogen fertilizer reduction with bio-organic fertilizer altered the abundance and diversity of soil bacteria, which was reduced compared to CF treatments. The PCoA analysis of the soil bacterial community showed that the community structure of NF-25% treatment was more different from other treatments, indicating that the fertilization method changed the community structure of soil bacteria. The results of a redundancy analysis showed that SOM, pH, AN, TN, and AP were the main factors affecting the microbial community structure. Overall, the reduction of nitrogen fertilizer with bio-organic fertilizer significantly increased the soil nutrient content, reduced the relative abundance and diversity of soil bacteria, increased the relative abundance of beneficial bacteria in the soil, changed the bacterial community structure of soil, increased production and created suitable soil conditions for the red raspberry growth.

Selenium application during fruit development can effectively inhibit browning of fresh-cut apples by enhancing antioxidant capacity and suppressing polyphenol oxidase activity.

Browning is a crucial factor affecting the quality of fresh-cut apples. A safe, simple, and effective method to inhibit browning is urgently needed in fresh-cut apple production. We carried out this study to explore the effect mechanism of exogenous selenium (Se) fertilizer on fresh-cut apple browning. During the development of apples, 0.75 kg/plant Se fertilizer was exerted on the 'Fuji' apple tree at the critical stage of the young fruit stage (late May), early fruit expansion stage (late June), and fruit expansion stage (late July), an equal amount of Se-free organic fertilizer was used as control. Polyphenol oxidase (PPO), peroxidase (POD), and phenylalanine ammonia-lyase (PAL) activities, phenolic and malondialdehyde (MDA) content, antioxidant enzymes activity, and DPPH free radical scavenging rate of the apple at different development stages were investigated. The highest Se accumulation efficiency was observed in apple fruit one month after applying Se fertilizer, which was 41.1%. Se-rich apples exhibited a more remarkable ability to resist browning than control after fresh-cut. The anti-browning effect of the fertilization group (M7) was the best, the PPO activity decreased to 0.5 × 103 U kg-1, and the browning index was 28.6. The total Se content (TSC) of 331.4 µg kg-1 DW and organic Se content (OSC) of 292.0 µg kg-1 DW were the highest in the apple samples, reached the classification standard of Se content in Se-rich food. The correlation analysis found that fresh-cut apple browning was closely related to antioxidant capacity and PPO activity. The stronger the antioxidant capacity of fresh-cut apples treated with Se fertilizer, the lower their browning degree. Therefore, exogenous Se can alleviate fresh-cut apples browning by improving antioxidant capacity and reducing PPO activity. Se-rich apples could increase the Se content of the human essential trace element and inhibit the browning of fresh-cut apples, which would become a new, safe and effective way to solve the fresh-cut apples browning.

Effect of acupuncture on episodic memory for amnesia-type mild cognitive impairment: study protocol of a multicenter, randomized, controlled trial.

BACKGROUND: Amnesic mild cognitive impairment (aMCI) is the main subtype of mild cognitive impairment (MCI) and has the highest risk of conversion to Alzheimer's disease (AD) among all MCI subtypes. Episodic memory impairment is the early cognitive impairment of aMCI, which has become an important target for AD prevention. Previous clinical evidence has shown that acupuncture can improve the cognitive ability of MCI patients. This experiment aimed to observe the efficacy and neural mechanism of TiaoshenYizhi acupuncture on the episodic memory of patients with aMCI. METHODS: In this multicenter, parallel-group, double-blind, randomized controlled trial, 360 aMCI participants will be recruited from six subcenters and randomly assigned to the acupuncture group, sham acupuncture group, and control group. The acupuncture group will receive TiaoshenYizhi (TSYZ) acupuncture, the sham acupuncture group will use streitberger sham acupuncture, and the control group will only receive free health education. Participants in the two acupuncture groups will receive real acupuncture treatment or placebo acupuncture three times per week, 24 sessions over 8 consecutive weeks. The primary outcome will be global cognitive ability. Secondary outcomes will be a specific cognitive domain, including episodic memory and execution ability, electroencephalogram, and functional magnetic resonance imaging data. Outcomes will be measured at baseline and the fourth and eighth weeks after randomization. Repeated measurement analysis of variance and a mixed linear model will be used to observe the intervention effect. DISCUSSION: The protocol will give a detailed procedure to the multicenter clinical trial to further evaluate the efficacy and neural mechanism of TiaoshenYizhi acupuncture on episodic memory in patients with aMCI. From this research, we expect to provide clinical evidence for early aMCI management. TRIAL REGISTRATION: http://www.chictr.org.cn/edit.aspx?pid=142612&htm=4 , identifier: ChiCTR2100054009.

Methylene-Bridged Dimerization by Cu-Catalyzed Deconstructive C-C Cleavage of Oxacycloalkane.

Herein, we demonstrate the successful utilization of copper catalysis and oxygen oxidation for consecutive C(sp3)-C(sp3) bond cleavage in alkyl cyclic ethers. A key step involves a copper-oxygen autoxidation process, generating in situ alkoxy radicals and triggering sequential C-C bond cleavage. This ß-oxidative cleavage strategy enables the use of cyclic ethers as valuable C1 building blocks for the synthesis of bridged methylene dimers. This reaction holds promise for inspiring alternative methods targeting inert C(sp3)-C(sp3) bond cleavage.

[Research progress in role of autophagy in diabetic wound healing and traditional Chinese medicine intervention].

Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.