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Abstract We propose a novel miniaturized optical attenuator based on the evanescent-field coupling between two nanofibers. Benefiting from a wavelength-dependent waveguiding property of the coupled structure, a tunable attenuation with maximum extinction ratio of ~ 20 dB is demonstrated with an ultrawide optical bandwidth up to 0.7 μm in experiment. The wavelength-depended waveguiding properties of both one single nanofiber and coupled nanofibers are investigated in both theory and simulation. Using an adiabatic coupling structure, an attenuation range from − 0.16 dB to − 18.46 dB is obtained within a spectrum from 1.2 μm to 1.7 μm experimentally. Moreover, the simulated results indicate that, the attenuation only shows a slight change of ~ 0.1 dB with a lateral misalignment of 0.5 μm between the two nanofibers, indicating a high tolerance of this attenuator to the lateral misalignment. Considering the wide bandwidth as well as the ultracompact structure, this attenuator shows high potential in applications such as all-fiber optical sensing and communicating.

Objective This study aimed to investigate the effects of dietary supplementation with Agaricus blazei polysaccharide (ABP) at varying concentrations on the performance, egg quality, blood biochemistry, intestinal morphology, and microflora of quail. Methods The study involved a total of 2,700 Korean quails, which were randomly divided into three groups. The measured variables encompassed productive performance, egg parameters, carcass parameters, serum metabolites, immune response parameters, antioxidative properties, and gut microbiome. Results The addition of ABP did not have a significant effect on average daily feed intake. However, it was found to increase the average daily egg weight and egg production rate, reduce the feed-egg ratio. There were no significant impacts on egg quality measures such as egg shape index, egg yolk index and color, egg yolk and protein content. However, ABP supplementation significantly increased the Hough unit (p

Abstract Background The aim of this study was to investigate the associations of blood phosphorus levels with the risk of developing medial arterial calcification (MAC) in lower-limb arteries and diabetic foot (DF) in diabetes patients. We sought to enhance the understanding of the pathophysiology of diabetic complications and develop strategies to mitigate diabetes-related risks. Methods We conducted a retrospective analysis of 701 diabetic patients from the Department of Endocrinology at Sun Yat-Sen Memorial Hospital (2019–2023). We utilized multimodel-adjusted logistic regression to investigate the associations of serum phosphorus levels and the risk of developing MAC and DF. Restricted cubic spline plots were employed to model the relationships, and threshold analysis was used to identify inflection points. Subgroup analyses were performed to explore variations across different demographics. The diagnostic utility of phosphorus concentrations was assessed via the C index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results Of the 701 patients (mean age 63.9 years; 401 (57.20%) were male), 333 (47.50%) had MAC, and 329 (46.93%) had DF. After controlling for numerous confounding variables, each one-unit increase in phosphorus concentrations was associated with an increased risk of developing MAC (OR 2.65, 95% CI 1.97–3.57, p

Background: Cold environments pose serious threats on human health, with increased risk for myocardial infarction, stroke, frostbite, and hypothermia. Acquired cold acclimation is required to minimize cold-induced injures and to improve metabolic health. However, the underlying mechanisms remain to be fully elucidated. Objective: We aimed to identify critical amino acids involved in cold acclimation and unmask the regulatory mechanisms. Methods: A total of twenty male participants were recruited and followed up after 3 months’ natural cold exposure. Cold-induced vasodilation (CIVD) tests and clinical biochemical analysis were performed at baseline and after 3-months cold exposure, whilst blood samples were collected, and plasma amino acids were analyzed by targeted metabolomics. To further confirm the effect of lysine on cold tolerance and explain the latent mechanism, mice were challenged with chronic cold exposure for 7 days with lysine supplement, then core and local surface temperature as well as thermogenesis activity were detected. Results: Continuous cold exposure shortened the CIVD onset time and increased the average finger temperature. Levels of the plasma lysine and glycine were decreased in both humans and mice. Venn analysis from three datasets revealed that lysine was the only significantly changed plasma amino acid, which strongly correlated with the altered CIVD. Moreover, mice sustained a relatively higher core temperature and surface temperature in the back, tail and paws upon lysine supplementation. Furthermore, lysine supplementation increased the level of histone H3K18cr and promoted the gene and protein expression of Cpt1a, Cpt2 and Cyp27a1 in liver. Conclusion: Our work identified lysine as a critical amino acid for the remodeling of hepatic histone crotonylation that facilitates cold acclimation.

The escalating prevalence of non-alcoholic fatty liver disease (NAFLD), driven by inadequate dietary habits and metabolic imbalances, underscores the urgent need for effective dietary interventions. This study investigated the potential of 80 % peanut diacylglycerol (DAG) as a functional lipid component in preventing NAFLD and associated intestinal microenvironment based on a high-cholesterol diet (HCD)-induced zebrafish model. We first found that the zebrafish fatty liver model shared multiple similar pathways like lipid-induced atherosclerosis, insulin resistance with NAFLD patient in terms of lipid metabolism. Employing larvae and grown zebrafish, we aimed to elucidate the preventive and alleviating effect of a DAG diet on NAFLD respectively. Results showed that DAG post-intervention significantly decreased hepatic lipid accumulation and diminished intestinal inflammatory in fatty liver zebrafish model. Notably, transcriptomic sequencing illuminated upregulation in genes related to lipid metabolism (e.g., fasn, mogat2, cd36), suggesting that peanut DAG accelerated lipid transportation and fostered a metabolic environment less conducive to NAFLD symptoms. Besides, reduced liver lipid droplets and hepatic inflammatory suggested DAG feeding could also prevent the formation of NAFLD. The study provided compelling evidence supporting the incorporation of DAG into the diet as a strategy for the prevention and management of fatty liver disease, proposing a novel approach to functional food development aimed at combating metabolic diseases.

ABSTRACT: This study was performed to investigate the effects of potassium diformate (KDF) on growth performance, apparent digestibility of nutrients, serum biochemical indices, and intestinal microflora of Cherry Valley ducks. In total, 144 female healthy 1-day-old Cherry Valley ducks were divided into 3 groups with 6 replicates per group and 8 ducks per replicate according to the principle of similar body weight. The control group was fed a basic diet. In the 2 experimental groups, 0.8% and 1.2% KDF was added to the basic diet, respectively. The trial period was 6 wk and the pretrial period was 3 wk. The final weight and ADG were significantly higher in the 0.8% KDF group than in the control group (P < 0.05). The feed-to-gain ratio was significantly lower in both KDF groups than in the control group (P < 0.05). The apparent digestibility of CP was significantly higher in both KDF groups than in the control group (P < 0.05). The apparent digestibility of calcium was also significantly higher in the 0.8% KDF group (P < 0.05). The serum levels of alkaline phosphatase, cholesterol, and total protein were significantly lower in the 0.8% KDF group than in the control group (P < 0.05), the IgM content was significantly higher (P < 0.05), the low-density lipoprotein cholesterol, triglyceride, and urea levels were significantly lower (P < 0.01), and the glucose level was significantly higher (P < 0.01). The serum total protein level was significantly higher in the 1.2% KDF group than in the control group (P < 0.05). The relative abundance of Firmicutes and Patescibacteria in the gut of ducks was significantly higher in the 0.8% KDF group than in the control group (P < 0.05), the relative abundance of unclassified Erysipelotrichaceae and Lactobacillus was significantly higher (P < 0.01), and the relative abundance of Fusobacteriota was significantly lower (P < 0.05). However, the relative abundance of Firmicutes in the gut of ducks was significantly higher in the 1.2% KDF group than in the control group (P < 0.05). The relative abundance of unclassified Erysipelotrichaceae and Clostridium sensu stricto 1 was significantly higher (P < 0.01), as was the relative abundance of Fusobacteriota and Proteobacteria (P < 0.05). These findings indicate that the addition of 0.8% KDF to the diet can improve the growth performance of Cherry Valley ducks, promote the absorption of nutrients, change the structure of the microflora in the cecum, and increase the relative abundance of dominant bacteria. It was also shown that there was a significant difference between the 0.8% and 1.2% KDF levels which suggest that the safety margin for overdosing is quite low.

BackgroundAlthough the Chufeng Qingpi Decoction (CQD) has demonstrated clinical effectiveness in the treatment of schistosomiasis, the precise active components and the underlying mechanisms of its therapeutic action remain elusive. To achieve a profound comprehension, we incorporate network pharmacology, bioinformatics analysis, molecular docking, and molecular dynamics simulations as investigative methodologies within our research framework.MethodUtilizing TCMSP and UniProt, we identified formula components and targets. Cytoscape 3.10.0 was used to construct an herb–target interaction network. Genecards, DisGeNET, and OMIM databases were examined for disease-related objectives. A Venn diagram identified the intersection of compound and disease targets. Using Draw Venn, overlapping targets populated STRING for PPI network. CytoNCA identified schistosomiasis treatment targets. GO & KEGG enrichment analysis followed High-scoring genes in PPI were analyzed by LASSO, RF, SVM-RFE. Molecular docking & simulations investigated target-compound interactions.ResultThe component’s target network encompassed 379 nodes, 1629 edges, highlighting compounds such as wogonin, kaempferol, luteolin, and quercetin. Amongst the proteins within the PPI network, PTGS2, TNF, TGFB1, BCL2, TP53, IL10, JUN, MMP2, IL1B, and MYC stood out as the most prevalent entities. GO and KEGG revealed that mainly involved the responses to UV, positive regulation of cell migration and motility. The signal pathways encompassed Pathways in cancer, Lipid and atherosclerosis, Fluid shear stress and atherosclerosis, as well as the AGE-RAGE. Bioinformatics analysis indicated TP53 was the core gene. Ultimately, the molecular docking revealed that wogonin, kaempferol, luteolin, and quercetin each exhibited significant affinity in their respective interactions with TP53. Notably, kaempferol exhibited the lowest binding energy, indicating a highly stable interaction with TP53. Lastly, we validated the stability of the binding interaction between the four small molecules and the TP53 through molecular dynamics simulations. The molecular dynamics simulation further validated the strongest binding between TP53 and kaempferol. In essence, our research groundbreaking in its nature elucidates for the first time the underlying molecular mechanism of CQD in the therapeutic management of schistosomiasis, thereby providing valuable insights and guidance for the treatment of this disease.ConclusionThis study uncovered the efficacious components and underlying molecular mechanisms of the Chufeng Qingpi Decoction in the management of schistosomiasis, thereby offering valuable insights for future fundamental research endeavors.

The adverse impacts of chronic hypoxia on maternal and infant health at high altitudes warrant significant attention. However, effective protective measures against the resultant growth restrictions and neurodevelopmental disorders in infants and young children are still lacking. This study investigated the neurodevelopment of mice offspring under hypoxic conditions by exposing pregnant mice to a hypobaric oxygen chamber that simulated the hypobaric hypoxia at an altitude of 4000 m until 28 days after delivery. Our findings suggested that prolonged exposure to hypoxia might result in emotional abnormalities and social disorders in offspring. The significant reduction in astrogliogenesis was a characteristic feature associated with neurodevelopmental disorders induced by hypoxia. Further studies demonstrated that cold-induced RNA-binding protein (CIRBP) was a key transcriptional regulator in astrogliogenesis, which downregulated astrocytic differentiation under hypoxia through its crosstalk with the NFIA. Our study emphasized the crucial role of CIRBP in regulating astrogliogenesis and highlighted its potential as a promising target for therapeutic interventions in neurodevelopmental disorders associated with hypoxia.

Abstract Parkinson's Disease (PD) is a complex, degenerative disease that affects nerve cells that are responsible for body movement. Artificial Intelligence (AI) algorithms are widely used to diagnose and track the progression of this disease, which causes symptoms of Parkinson's disease in its early stages, by predicting the results of the Unified Parkinson's Disease Rating Scale (UPDRS). In this study, we aim to develop a method based on the integration of two methods, one complementary to the other, Ensembles of Self-Organizing Map and Neuro-Fuzzy, and an unsupervised learning algorithm. The proposed method relied on the higher effect of the variables resulting from the analysis of the initial readings to obtain a correct and accurate preliminary prediction. We evaluate the developed approach on a PD dataset including speech cues. The process was evaluated with root mean square error (RMSE) and modified R square (modified R2). Our findings reveal that the proposed method is effective in predicting UPDRS outcomes by a combination of speech signals (measures of hoarseness). As the preliminary results during the evaluation showed numbers that proved the worth of the proposed method, such as UPDRS = 0.955 and RMSE approximately 0.2769 during the prediction process.

Optical micro/nanofibers (MNFs) taper-drawn from silica fibers possess intriguing optical and mechanical properties. Recently, MNF array or MNFs with identical geometries have been attracting more and more attention, however, current fabrication technique can draw only one MNF at a time, with a low drawing speed (typically 0.1 mm/s) and a complicated process for high-precision control, making it inefficient in fabricating multiple MNFs. Here, we propose a parallel-fabrication approach to simultaneously drawing multiple (up to 20) MNFs with almost identical geometries. For fiber diameter larger than 500 nm, measured optical transmittances of all as-drawn MNFs exceed 96.7% at 1550-nm wavelength, with a diameter deviation within 5%. Our results pave a way towards high-yield fabrication of MNFs that may find applications from MNF-based optical sensors, optical manipulation to fiber-to-chip interconnection.

Torrential bleeding is a rare and life-threatening complication of arteriovenous malformations (AVMs). We report a case of head and neck AVMs present with uncontrollable torrential bleeding, which was treated with embolization and sclerotherapy. Then we explored the potential multidisciplinary handling of the procedure for this kind of case. A 25-year-old female patient was born with right face and head AVMs. The AVMs had grown gradually and ruptured spontaneously with uncontrollable torrential bleeding before admission. Emergent direct hemostasis, nasotracheal intubation, and staged embolization and sclerotherapy were carried out on this patient. Finally, the bleeding stopped and the wound healed successfully. Embolization and sclerotherapy are effective for head and neck AVMs with uncontrollable torrential bleeding. Multidisciplinary collaboration is needed to achieve a good outcome.

Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide. The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases. Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf, but their mechanism of action has still not fully elucidated. We synthesized Moracin N (MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis. MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells. Chemical proteomic results showed that MAN targeted the programmed death ligand 1 (PD-L1) checkpoint pathway and T cell receptor (TCR) signaling pathway, indicating its immune-regulatory function. Cell-free surface plasmon resonance (SPR) results showed the direct interaction of MAN with PD-L1 protein. Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein. MAN downregulated the expression levels of PD-L1 in a time- and dose-dependent manner and disrupted the PD-L1/programmed death 1 (PD-1) binding, including other secondary metabolites of mulberry leaves Guangsangon E (GSE) and Chalcomoracin (CMR). Human peripheral blood mononuclear cells (PBMCs) co-cultured with MAN-treated A549 cells, resulting in the increase of CD8+ GZMB+ T cells and the decrease of CD8+ PD-1+ T cells. It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling. In vivo, MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis, indicating their synergistic effect. Taken together, secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling, enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer. Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.

In this study, we propose a model called CNN-BiLSTM-AM that utilizes deep learning techniques to forecast severe convective weather based on ERA5 hourly data and observations. The model integrates a CNN with a Bidirectional Long Short-Term Memory (BiLSTM) system and an Attention Mechanism (AM). The CNN is tasked with extracting features from the input data, while the BiLSTM effectively captures temporal dependencies. The AM enhances the results by considering the impact of past feature states on severe weather phenomena. Additionally, we assess the performance of our model in comparison to traditional network architectures, including ConvLSTM, Predrnn++, CNN, FC-LSTM, and LSTM. Our results indicate that the CNN-BiLSTM-AM model exhibits superior accuracy in precipitation forecasting. Especially with the extension of the forecast time, the model performs well across multiple evaluation metrics. Furthermore, an interpretability analysis of the convective weather mechanisms utilizing machine learning highlights the critical role of total precipitable water (PWAT) in short-term heavy precipitation forecasts. It also emphasizes the significant impact of regional variables on convective weather patterns and the role of convective available potential energy (CAPE) in fostering conditions conducive to convection. These findings not only confirm the effectiveness of deep learning in the automatic identification of severe weather features but also validate the suitability of the sample dataset employed. Given its remarkable performance and robustness, we advocate for the adoption of this model to enhance the forecast of severe convective weather across various business applications.

IntroductionAcupuncture is a Traditional Chinese Medicine (TCM) method that achieves therapeutic effects through the interaction of neurotransmitters and neural regulation. It is generally carried out manually, making the related process expert-biased. Meanwhile, the neural stimulation effect of acupuncture is difficult to track objectively. In recent years, virtual reality (VR) in medicine has been on the fast lane to widespread use, especially in therapeutic stimulation. However, the use of related technologies in acupuncture has not been reported.MethodsIn this work, a novel acupuncture stimulation technique using VR is proposed. To track the stimulation effect, the electroencephalogram (EEG) is used as the marker to validate brain activities under acupuncture.Results and discussionAfter statistically analyzing the data of 24 subjects during acupuncture at the “Zusanli (ST36)” acupoint, it has been determined that Virtual Acupuncture (VA) has at least a 63.54% probability of inducing similar EEG activities as in Manual Acupuncture (MA). This work may provide a new solution for researchers and clinical practitioners using Brain-Computer Interface (BCI) in acupuncture.

Resistant starch (RS) is defined as the total amount of starch and the products of starch degradation that resists digestion and absorption in the small intestine of the healthy human body within 120 min, but it can be fermented in the large intestine. It provides many health benefits for humans, such as preventing diabetes, improving the intestinal microenvironment, reducing blood sugar, blood fat and weight, thus sparking great interest of scholars in multiple fields such as agriculture, food and medicine. RS has become one of the hot topics in crop nutrition quality improvement and healthy food research. According to the different chemical structures, sources and properties, RS can be divided into five types: RS1, RS2, RS3, RS4 and RS 5. Banana is the world's largest traded fruit, the fourth largest food crop, and a source of carbohydrates for two billion people worldwide. Banana RS belongs to the RS2 type and is the only RS identified as dietary fiber by the US Food and Drug Administration. Banana fruit is rich in RS, with a content of over 40% in unripen fruit, which is much higher than that in rice (< 3.0%), wheat (< 3.5%), high amylose corn (< 22.4%) and other crops. Banana is a direct source of functional food. Since British physiologist Englyst first discovered and named RS in 1982, significant progresses have been made in bananas in terms of the morphological characteristics of RS granules, effects of processing conditions and complexation reaction on the morphological characteristics of RS granules, the relationship between accumulation and degradation characteristics and fruit quality, preparation methods and applications in food processing. However, compared to cereal crops like rice, studies on the core genes involved in RS synthesis, regulation mechanisms of transcription factors for the core genes expression influencing RS synthesis, functional identification, and molecular breeding in banana are significantly lagging behind. The previous work on the cytology, physiology and biochemistry, food processing, molecular biology of banana RS since 1982 is reviewed, and prospect for future work is put forward.

Introducing an additive is a practical approach to improve the lubrication performance of base oil in the field of tribology. Herein, a series of sulfoximine derivatives was synthesized and incorporated into base oil A51 as additives. The tribological properties of these lubricants were evaluated at both room and high temperatures, and the result demonstrated that they displayed excellent friction reduction and wear resistance in the friction process under both test conditions. Moreover, the chemical composition of the worn scar surface was inspected using EDS, XPS and TOF-SIMS to explore the lubricating mechanism. It is reasonable to conclude that the synergistic interaction between the aromatic ring scaffolds and elements like N, F, and S facilitated the adsorption of lubricant on the steel block surfaces and forming a tribofilm during the friction process. This tribofilm has a dominant impact on the system’s lubrication performance. This research provides novel oil-soluble lubricant additives, offering a facile approach to formulating high-quality lubricants.

The excessive extraction of river sand has led to significant ecological issues. Moreover, the environmental impact and resource demand of cement production have increasingly turned the spotlight on sea sand as a viable alternative due to its abundance and ease of extraction. Concurrently, alkali-activated binders, a novel type of low-carbon cementitious material, have gained attention for their low energy consumption, high durability, and effective chloride ion fixation capabilities. However, they are susceptible to carbonation. Introducing a controlled sea sand amount can raise the materials’ carbonation resistance, although carbonation may raise the concentration of free Cl− within the structure to levels that could risk the integrity of steel reinforcements by accelerating corrosion. In this context, the current study investigates sea sand alkali-activated slag (SSAS) concrete prepared with varying water–binder (W/B) ratios to evaluate its impact on flowability, mechanical strength, performances, and chloride ion distribution post-carbonation. The results demonstrate that the mechanical property of SSAS concrete diminishes as the water-to-binder ratio increases, with a more pronounced reduction observed. The depth of carbonation in mortar specimens also rises with the W/B ratio, whereas the compressive strength post-carbonation initially decreases before showing an increase as carbonation progresses. Furthermore, carbonation redistributes chloride ions in SSAS, leading to a peak Cl− concentration near the carbonation front. However, this peak amplitude does not show a clear correlation with changes in the W/B ratio. This study provides a theoretical foundation for employing sea sand and alkali-activated concrete.

Excessive long-term manganese intake can inflict irreversible damage to the nervous system, with a predominant effect on the substantia nigra-striatum pathway. Through a mouse model simulating manganese exposure, we delved into its implications on the central nervous motor system, uncovering autophagy-lysosome dysfunction as a pivotal factor in manganese-induced neurotoxicity. Our research illuminated the molecular mechanisms behind TFEB’s role in manganese-triggered neuronal autophagy dysfunction, offering insights into the cellular and molecular mechanisms of manganese-induced abnormal protein accumulation. This study lays a significant theoretical foundation for future endeavors aimed at safeguarding against manganese neurotoxicity. Furthermore, TFEB emerges as a potential early molecular biomarker for manganese exposure, providing a solid basis for preemptive protection and clinical treatment for populations exposed to manganese.

Glutathione peroxidase 2 (GPX2) is a selenium-dependent enzyme and protects cells against oxidative damage. Recently, GPX2 has been identified as a candidate gene for backfat and feed efficiency in pigs. However, it is unclear whether GPX2 regulates the development of porcine preadipocytes and skeletal muscle cells. In this study, adenoviral gene transfer was used to overexpress GPX2. Our findings suggest that overexpression of GPX2 gene inhibited proliferation of porcine preadipocytes. And the process is accompanied by the reduction of the p-p38. GPX2 inhibited adipogenic differentiation and promoted lipid degradation, while ERK1/2 was reduced and p-p38 was increased. Proliferation of porcine skeletal muscle cells was induced after GPX2 overexpression, was accompanied by activation in JNK, ERK1/2, and p-p38. Overexpression methods confirmed that GPX2 has a promoting function in myoblastic differentiation. ERK1/2 pathway was activated and p38 was suppressed during the process. This study lays a foundation for the functional study of GPX2 and provides theoretical support for promoting subcutaneous fat reduction and muscle growth.

AbstractObjectives To construct a valid and reliable Nutritional Literacy Scale for patients with end-stage kidney disease (ESKD) receiving dialysis and evaluate associations between nutrition literacy and quality of life.Methods A total of 208 ESKD patients receiving dialysis were selected for this study. Nutrition literacy evaluation items were drafted based on dietary guidelines for chronic kidney disease (CKD), Literature reviews and expert consultation. Scale reliability and validity were then assessed. Factors influencing nutrition literacy and the associations among nutrition literacy, nutritional status, and quality of life were evaluated.Results The scale consists of 28 items with a scale-level content validity index of 0.91 and item-level content validity indices ranging from 0.83 to 1.00. Factor analysis identified 4 common factors (dimensions) named nutrition knowledge, cognitive attitude, behavioral practice, and information acquisition ability that collectively explained 56.31% of literacy score variation. The overall Cronbach’s α coefficient of the scale was 0.83, the dimensional Cronbach’s α coefficients ranged from 0.79 to 0.87, and the retest reliability was r = 0.73 (p

Abstract Background Sunflower is an important ornamental plant, which can be used for fresh cut flowers and potted plants. Plant architecture regulation is an important agronomic operation in its cultivation and production. As an important aspect of plant architecture formation, shoot branching has become an important research direction of sunflower. Results TEOSINTE-BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors are essential in regulating various development process. However, the role of TCPs in sunflowers has not yet been studied. This study, 34 HaTCP genes were identified and classified into three subfamilies based on the conservative domain and phylogenetic analysis. Most of the HaTCPs in the same subfamily displayed similar gene and motif structures. Promoter sequence analysis has demonstrated the presence of multiple stress and hormone-related cis-elements in the HaTCP family. Expression patterns of HaTCPs revealed several HaTCP genes expressed highest in buds and could respond to decapitation. Subcellular localization analysis showed that HaTCP1 was located in the nucleus. Paclobutrazol (PAC) and 1-naphthylphthalamic acid (NPA) administration significantly delayed the formation of axillary buds after decapitation, and this suppression was partially accomplished by enhancing the expression of HaTCP1. Furthermore, HaTCP1 overexpressed in Arabidopsis caused a significant decrease in branch number, indicating that HaTCP1 played a key role in negatively regulating sunflower branching. Conclusions This study not only provided the systematic analysis for the HaTCP members, including classification, conserved domain and gene structure, expansion pattern of different tissues or after decapitation. But also studied the expression, subcellular localization and function of HaTCP1. These findings could lay a critical foundation for further exploring the functions of HaTCPs.

We demonstrate CW optical waveguiding in a silica MNF with power up to 13 W, making it possible for high-speed optomechanical driving of microparticles, and efficient second/third harmonic generation.

Systematic biases and coarse resolutions are major limitations of current precipitation datasets. Many studies have been conducted for precipitation bias correction and downscaling. However, it is still challenging for the current approaches to handle the complex features of hourly precipitation, resulting in the incapability of reproducing small-scale features, such as extreme events. In this study, we proposed a deep-learning model called PBT (Population-Based Training)-GRU (Gate Recurrent Unit) based on numerical model NWP gridded forecast data and observation data and employed machine-learning (ML) methods, such as Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), and Gradient-Boosted Decision Tree (GBDT), to correct the WRF hourly precipitation forecasts. To select the evaluation method, we conducted a sample balance experiment and found that when the proportion of positive and negative samples was 1:1, the Threat Score (TS) and accuracy scores were the highest, while the Probability of Detection (POD) score was slightly lower. The results showed that: (1) the overall errors of the PBT-GRU model were relatively smaller, and its root mean square error (RMSE) was only 1.12 mm, which was reduced by 63.04%, 51.72%, 58.36%, 37.43%, and 26.32% compared to the RMSE of WRF, SVM, KNN, GBDT, and RF, respectively; and (2) according to the Taylor diagram, the standard deviation (σn) and correlation coefficient (r) of PBT-GRU were 1.02 and 0.99, respectively, while the σn and r of RF were 1.12 and 0.98, respectively. Furthermore, the σn and r of the SVM, GBDT, and KNN models were between those of the above models, with values of 1.24 and 0.95, 1.15 and 0.97, and 1.26 and 0.93, respectively. Based on a comprehensive analysis of the TS, accuracy, RMSE, r and σn, the PBT-GRU model performed the best, with a significantly better correction effect than that of the ML methods, resulting in an overall performance ranking of PBT-GRU > RF > GBDT > SVM > KNN. This study provides a hint of the possibility that the proposed PBT-GRU model can outperform model precipitation correction based on a small sample of one-station data. Thus, due to its promising performance and excellent robustness, we recommend adopting the proposed PBT-GRU model for precipitation correction in business applications.

The advancement of Numerical Weather Prediction (NWP) is pivotal for enhancing high-impact weather forecasting and warning systems. However, due to the high spatial and temporal inhomogeneity, the moisture field is difficult to describe by initial conditions in NWP models, which is the essential thermodynamic variable in the simulation of various physical processes. Data Assimilation techniques are central to addressing these challenges, integrating observational data with background fields to refine initial conditions and improve forecasting accuracy. This study evaluates the effectiveness of integrating observations from the Fengyun-4A (FY-4A) Advanced Geosynchronous Radiation Imager (AGRI) and ground-based microwave radiometer (MWR) in forecasts and mechanism analysis of a heavy rainfall event in the Kaifeng region of central China. Our findings reveal that jointly assimilating AGRI radiance and MWR data significantly enhances the model’s humidity profile accuracy across all atmospheric layers, resulting in improved heavy rainfall predictions. Analysis of the moisture sources indicates that the storm’s water vapor predominantly originates from westward air movement ahead of a high-altitude trough, with sustained channeling towards the rainfall zone, ensuring a continuous supply of moisture. The storm’s development is further facilitated by a series of atmospheric processes, including the interplay of high and low-level vorticity and divergence, vertical updrafts, the formation of a low-level jet, and the generation of unstable atmospheric energy. Additionally, this study examines the influence of Tai-hang Mountain’s terrain on precipitation patterns in the Kaifeng area. Our experiments, comparing a control setup (CTL) with varied terrain heights, demonstrate that reducing terrain height by 50–60% significantly decreases precipitation coverage and intensity. In contrast, increasing terrain height enhances precipitation, although this effect plateaus when the elevation increase exceeds 100%, closely mirroring the precipitation changes observed with a 75% terrain height increment.

Abstract Background Insulin‐like growth Factor 2 mRNA‐binding protein 3 (IGF2BP3) is a highly conserved RNA‐binding protein and plays a critical role in regulating posttranscriptional modifications. Methods Immunoprecipitation was used to examine the interaction of Parkin and IGF2BP3. Mass spectrometry was performed to identify the ubiquitination sites of IGF2BP3. RNA‐immunoprecipitation was conducted to examine the target genes of IGF2BP3. Xenograft mouse model was constructed to determine the tumorigenesis of IGF2BP3. Results IGF2BP3 expression is negatively correlated with Parkin expression in human cervical cancer cells and tissues. Parkin directly interacts with IGF2BP3, and overexpression of Parkin causes the proteasomal degradation of IGF2BP3, while knockdown of PARK2 increases the protein levels of IGF2BP3. Mechanistically, in vivo and in vitro ubiquitination assays demonstrated that Parkin is able to ubiquitinate IGF2BP3. Moreover, the ubiquitination site of IGF2BP3 was identified at K213 in the first KH domain of IGF2BP3. IGF2BP3 mutation results in the loss of its oncogenic function as an m6A reader, resulting in the inactivation of the phosphoinositide 3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK) signalling pathways. In addition, IGF2BP3 mutation results in the attenuation of Parkin‐mediated mitophagy, indicating its inverse role in regulating Parkin. Consequently, the tumourigenesis of cervical cancer is also inhibited by IGF2BP3 mutation. Conclusion IGF2BP3 is ubiquitinated and regulated by the E3 ubiquitin ligase Parkin in human cervical cancer and ubiquitination modification plays an important role in modulating IGF2BP3 function. Thus, understanding the role of IGF2BP3 in tumourigenesis could provide new insights into cervical cancer therapy.

The ϵ-spectral radius of a connected graph is the largest eigenvalue of its eccentricity matrix. In this paper, we identify the unique n-vertex tree with diameter 4 and matching number 5 that minimizes the ϵ-spectral radius, and thus resolve a conjecture proposed in [W. Wei, S. Li, L. Zhang, Characterizing the extremal graphs with respect to the eccentricity spectral radius, and beyond, Discrete Math. 345 (2022) 112686].

Abstract Background Multiple ground-glass nodules (mGGNs) in the lung has been defined as synchronous multiple primary lung cancer (SMPLC), it is has been very difficult challenging to differentiate SMPLC from intrapulmonary metastases, and its treatment remains controversial. Case presentation We report a case simultaneously involving mGGNs and lung adenocarcinoma harboring primary EGFR-T790M mutation, in which the patient underwent the radical resection of lesions in the left upper lung, and continued the osimertinib treatment for the residual mGGNs in all lobes of the right lung. These mGGNs displayed different responses to osimertinib. Conclusions We reported a successful strategy on the postoperative treatment for mGGNs. For those that cannot be completely resected, the chemotherapy, radiotherapy, stereotactic body radiation therapy, immunotherapy and targeted therapy have been performed instead. The EGFR-TKI therapy strategy showed significant advantages, but how to achieve even better therapeutic effect needs more researches.

Effective chemotherapy for clinical treatment of brain diseases is still lacking due to the poor penetration of the blood-brain barrier (BBB). The aim of this study was to construct a folate modified pterostilbene (Pt) loaded polymeric micellar delivery system (F-Pt/M) with mPEG-PCL as carrier material to aim at penetrating the BBB for brain tissue targeting via receptor-mediated endocytosis. In this study, F-Pt/M was prepared using thin-film hydration method and then optimized by response surface methodology (RSM) with the entrapment efficiency (EE), drug loading (DL) and hydrodynamic diameter (HD) as indexes. The average hydrodynamic diameter and zeta potential of optimal F-Pt/M were 133.2 nm and 24.6 mV, respectively. DL (18.3%) and EE (98.6%) made the solubility of Pt in water about 25 times higher than that of crude Pt. Results of DSC evaluation revealed that drugs were successfully encapsulated inside the polymeric micelles. TEM images showed that homogeneous spherical micellar structures with a narrow size distribution were developed. The release result in vitro showed that F-Pt/M presented sustained release behavior compared to control free Pt solution. Compared to non-targeted Pt/M, F-Pt/M had a significantly higher cytotoxicity against FR-overexpressing A172 cells. In vitro cellular uptake tests illustrated that the micellar delivery system could significantly improve the accumulation of drugs in target cells via receptor-mediated endocytosis. BBB penetration value (P) of F-Pt/M was about 4 folds higher than that of free Pt group. In addition, drug targeting index (DTI) was calculated to determine targeting of F-Pt/M to the brain which was found to be 4.89, implying improved brain targeting was achieved. Hence, the developed F-Pt/M exhibited great potential for delivering more drug molecules across the BBB for the treatment of brain diseases.

Neurotoxicity caused by environmental lead (Pb) pollution is a worldwide public health concern, and developing a therapeutic strategy against Pb-induced neurotoxicity is an important area in the current research. Our prior research has demonstrated the significant involvement of microglia-mediated inflammatory responses in the manifestation of Pb-induced neurotoxicity. Additionally, the suppression of proinflammatory mediator activity significantly mitigated the toxic effects associated with Pb exposure. Recent studies have highlighted the critical role of the triggering receptor expressed on myeloid cells 2 (TREM2) in the pathogenesis of neurodegenerative disorders. TREM2 exerted protective effects on inflammation, but whether TREM2 is involved in Pb-induced neuroinflammation is poorly understood. In the present study, cell culture experiments and animal models were designed to investigate the role of TREM2 in Pb’s neuroinflammation. We examined the impact of pro- and anti-inflammatory cytokines involved in Pb-induced neuroinflammation. Flow cytometry and microscopy techniques were applied to detect microglia phagocytosis and migration ability. Our results showed that Pb treatment significantly downregulated TREM2 expression and altered the localization of TREM2 expression in microglia. The protein expression of TREM2 was restored, and the inflammatory responses provoked by Pb exposure were ameliorated upon the overexpression of TREM2. Furthermore, the phagocytosis and migratory capabilities of microglia, which were impaired due to Pb exposure, were alleviated by TREM2 overexpression. Our in vitro findings were corroborated in vivo, demonstrating that TREM2 regulates the anti-inflammatory functions of microglia, thereby mitigating Pb-induced neuroinflammation. Our results provide insights into the detailed mechanism by which TREM2 alleviates Pb-induced neuroinflammation and suggest that activating the anti-inflammatory functions of TREM2 may represent a potential therapeutic strategy against environmental Pb-induced neurotoxicity.

PurposeTo retrospectively report our preliminary experience of treating hand arteriovenous malformations (AVMs) with embolo/sclerotherapy.Materials and methodsRetrospectively review the demographics, treatment detail, outcome data, and complications of 13 consecutive patients with hand AVMs from January 2018 to December 2021. We embolize the dominant outflow vein with elastic coils and then use absolute ethanol or polidocanol for intravascular sclerotherapy and bleomycin for interstitial sclerotherapy.ResultsYakes type II presents in four lesions, type IIIa in six, and type IIIb in three. A total of 29 treatment episodes were conducted for the 13 patients (1 episode for 3 patients, 2 for 4 patients, and 3 for 6 patients; the repeated treatment rate was 76.9%). The mean stretched length of coils for 1 treatment episode was 95 cm. The mean absolute ethanol dosage was 6.8 ml (range 4–30 ml). In addition, 10 ml of 3% polidocanol foam was injected and interstitial sclerotherapy with 150,000 IU bleomycin was performed on every patient. The post-operative arterial-dominant outflow vein pressure index (AVI) increased in the 29 procedures (6.55 ± 1.68 vs. 9.38 ± 2.80, P

Background: Lead contamination is a major public health concern. Previous studies have demonstrated that lead exposure could affect the hippocampus, which is a complex and heterogeneous structure composed of 12 subregions. Here, we explored volumetric and functional changes in hippocampal subfields and neuropsychological alterations after lead exposure. Methods: We performed a cross-sectional study at a smelting company between September 2020 and December 2021. Blood lead level was recorded, and neuropsychological functions were assessed by Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). The hippocampus was segmented into 12 subfields in each hemisphere in magnetic resonance images (MRIs). Then, the effect of altered hippocampal subfield volumes on brain functions were studied by seed-based functional connectivity (FC) analysis. Finally, the relationships between the lead level with hippocampal subfield volumes and neuropsychological functions were investigated. Baseline characteristics, hippocampal subfield volumes, and FC analysis were compared between lead-exposed (≥ 300 μg/L) and the control group (≤ 100 μg/L). Results: In 76 participants, lead level positively correlated with SDS(r = 0.422) and negatively correlated with MoCA(r = −0.414), MMSE(r = −0.251), Concentration(r = −0.331), Recall(r = −0.319), Orientation(r = −0.298) and Executive Function/Visuospatial abilities(r = −0.231). Lead group (26 participants) had lower MoCA and MMSE and higher SDS than control group (23 participants). A significantly decreased volume in the left CA4 and GC-ML-DG subfields was found in the lead group compared with the control group. The left GC-ML-DG of the lead group showed a decreased FC with the bilateral postcentral gyrus. The left CA4(r = −0.409) and left GC-ML-DG (r = −0.383) volumes negatively correlated with lead level. The FC between left GC-ML-DG and left postcentral gyrus positively correlated with MoCA(r = 0.318), MMSE(r = 0.379) and Recall(r = 0.311). The FC between left GC-ML-DG and right postcentral gyrus positively correlated with MoCA(r = 0.326), Executive Function/Visuospatial abilities(r = 0.307) and Concentration(r = 0.297). Conclusion: High blood lead level was associated with neuropsychological alterations, hippocampal structural and functional changes. The left GC-ML-DG and CA4 atrophy might serve as predictive imaging markers for neurological damage associated with high lead exposure.

A simulation and sensitivity test of a rainstorm over Bosten Lake area of Xinjiang province on August 14， 2020 were done based on WRF4.0， and the mesoscale structure characteristics were analyzed.The results show that： （1）the rainstorm process was driven by the Iranian high pressure system， the Centra Asian trough moved eastward， and merged with the West Siberian trough in the Central Tianshan Mountains， forming a large trough from north to south.The Bosten Lake area was located in the center of the trough， and the southwest airflow in front of the trough was strong， which provided a favorable large-scale circulation background for the formation and development of the rainstorm process.（2） During the rainstorm， the water vapor was transported from the upper part of the Central Asia to the lower part of the mountain.（3）Atmospheric upward motion， favorable coupling situation of vorticity and divergence at high and low levels， existence of low-level jet and release of unstable energy in the atmosphere jointly triggered the occurrence of the rainstorm.（4） The sensitivity tests showed that， the Kuruktag Mountain had a significant impact on precipitation.When the height of the mountain decreased， the rainfall increased and the precipitation range increased.

The atom-bond connectivity energy (ABC energy) of an undirected graph $ G $, denoted by $ \mathcal{E}_{ABC}(G) $, is defined as the sum of the absolute values of the ABC eigenvalues of $ G $. Gao and Shao [The minimum ABC energy of trees, Linear Algebra Appl., 577 (2019), 186-203] proved that the star $ S_n $ is the unique tree with minimum ABC energy among all trees on $ n $ vertices. In this paper, we characterize the trees with the minimum ABC energy among all trees on $ n $ vertices except the star $ S_n $.

Abstract As the tight reservoir of Lucaogou Formation in Jimsar sag is characterized as large burial depth and poor physical properties, hydraulic fracturing technology is greatly needed to increase the production. Firstly, based on elastic theory, the borehole displacement formula under stress is derived, then the borehole quasi-ellipse characteristic model is proposed, on this basis, the in-situ stress prediction model based on borehole deformation is constructed. Secondly, the force analysis of diamond bit during drilling is performed, and the continuous prediction formula of elastic modulus based on weight on bit (WOB) and torque parameters is derived. Combined with these two steps, a new model of continuous in-situ stress prediction based on borehole deformation and drilling parameters is established. Compared with the values measured by the acoustic emission method in the laboratory, the deviation between the predicted in-situ stress values and those measured by the acoustic emission method is less than 4%, which meets the accuracy requirements of the fracturing in the oil field. The prediction results show that the minimum horizontal principal stress of Lucaogou Formation is 51.1–62.7 MPa, and the maximum horizontal principal stress is 58.9–69.1 MPa, respectively. The maximum horizontal principal stress direction is NW–SE direction with an angle of about 159°. The results show that the fracture direction in the study area is in accordance with the present in-situ stress direction, which is beneficial to the secondary reconstruction of natural fractures and keeps good opening property of fractures. This study provides a theoretical basis for in-situ stress prediction and compressibility evaluation of tight reservoir.

This paper assessed the positive effects of selenized-oligochitosan (SOC) on zearalenone(ZEN)-induced intestinal dysfunction in piglets. Sixty piglets were randomly divided into 4 groups. Group C was fed the basal diet as a control and Group Z was supplemented with 2 μg/g ZEN in the basal diet; Group ZS1 and ZS2 were supplemented with 0.3 or 0.5 μg/g SOC (calculated by selenium), in addition to 2 μg/g ZEN in the basal diet. After 42 days, ileal mucosal structure, digestive enzyme activities, tight junction protein mRNA expressions, plasma D-lactate and D-xylose contents, and plasma diamine oxidase activities were determined. Compare with Group C, ileal villus height, value of villus height/crypt depth, trypsin, lipase and α-amylase activities, occluding, claudin-1 and ZO-1 mRNA expressions, and plasma D-xylose levels were significantly decreased (p

Objective: Grain-sized moxibustion is an effective treatment for hyperlipidemia, but how it regulates dyslipidemia and liver lipid deposits still needs to be fully understood. This study explored the molecular biological mechanism of grain-sized moxibustion to regulate hepatic autophagy in hyperlipidemic rats by affecting ULK1 and TFEB through the AMPK/mTOR signaling pathway. Methods: Thirty male Sprague-Dawley (SD) rats were fed a high-fat diet for eight weeks to induce hyperlipidemia. Hyperlipidemic rats were divided into the HFD group, HFD + Statin group, HFD + CC + Moxi group, and grain-sized moxibustion intervention group (HFD + Moxi group). The control (Blank) group consisted of normal rats without any intervention. Grain-sized moxibustion and drug interventions were initiated eight weeks after high-fat diet induction and continued for ten weeks. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), as well as hepatic triglyceride (TG), were measured after treatment. Hepatic steatosis and the expression of LC3I, LC3II, p62, p-AMPK, AMPK, p-mTOR, mTOR, ULK1, p-ULK1, and TFEB in the liver were analyzed. Results: Compared with the HFD group, grain-sized moxibustion improved hyperlipidemia and hepatocyte steatosis, increased the LC3, p-AMPK, p-ULK1, and nuclear TFEB expression in the liver, but decreased the p62 and p-mTOR expression. Conclusion: Grain-sized moxibustion at ST36 acupoints could regulate the blood lipid level of SD rats with hyperlipidemia, increase the expression level of ULK1 and TFEB by activating the AMPK/mTOR signaling pathway in liver tissues, and initiate the transcription of autophagy genes such as LC3.

Background and aimsGalanin is a naturally occurring peptide that plays a critical role in regulating inflammation and energy metabolism, with expression in the liver. The exact involvement of galanin in non-alcoholic fatty liver disease and related fibrosis remains controversial.MethodsThe effects of subcutaneously administered galanin were studied in mice with non-alcoholic steatohepatitis (NASH) induced by a high-fat and high-cholesterol diet for 8 weeks, and in mice with liver fibrosis induced by CCl4 for 7 weeks. The underlying mechanism was also studied in vitro on murine macrophage cells (J774A.1 and RAW264.7).ResultsGalanin reduced inflammation, CD68-positive cell count, MCP-1 level, and mRNA levels of inflammation-related genes in the liver of NASH mice. It also mitigated liver injury and fibrosis caused by CCl4. In vitro, galanin had anti-inflammatory effects on murine macrophages, including reduced phagocytosis and intracellular reactive oxygen species (ROS). Galanin also activated AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling.ConclusionGalanin ameliorates liver inflammation and fibrosis in mice, potentially by modifying macrophage inflammatory phenotype and activating AMPK/ACC signaling.

IntroductionThe modernized lifestyle has been paralleled by an epidemic of inflammatory bowel disease (IBD). Excessive consumption of cold beverages is especially common among the modern humans. However, whether cold stress contributes directly to the gut barrier and gut–brain axis is not clear.MethodsWe conducted a cold stress model induced by cold water. The mice were treated with 14 consecutive days of intragastric cold or common water administration. We observed changes in gut transit and gut barrier in the colon. We also employed RNA sequencing-based transcriptomic analysis to identify the genes potentially driving gut injury, and simultaneously examined the gut microbiota and metabolites in the feces.ResultsWe found that cold stress disturbed the intestinal function and increased gut permeability. A set of core genes related to immune responses were consistently overexpressed in the cold stress group. Additionally, cold stress induced decreased bacterial diversity, ecological network, and increased pathogens mainly belonging to Proteobacteria. The dopamine signaling pathway-related metabolites were largely reduced in the cold stress group.ConclusionThis study revealed that cold stress could trigger an IBD-like phenotype in mice, implying that cold stress is a possible risk factor for IBD development.

As increasing number of people migrated to high altitude, highland encephalopathy and hypoxia-induced cognitive impairment arouse public attention. Yet, its underlying mechanisms remain unclear. Emerging evidence has implied neuroinflammation and neuronal loss may be involved. In the present study, we investigated the neuroinflammation and neuronal loss in mice after hypoxic insult. Our reports showed hypobaric hypoxia exposure for 3 weeks led to impaired spatial exploration and short-term memory in mice, concomitant with neuron loss. In addition, hypoxia induced neuroinflammation and NLRP3 inflammasome activation. Besides, to explore the role of the inflammasome in hypoxia-induced cognitive dysfunction, NLRP3 knockout mice were applied and the results showed that NLRP3 could negatively regulate GPX4 to modify antioxidant capacity. In summary, our work demonstrated that hypoxia exposure led to neuroinflammation and neuronal-deletion, which may be the key events in the process of hypoxia induced cognitive impairment. NLRP3 inflammasome promoted antioxidant deficiency by negatively regulating GPX4.

Rational design and preparation of multifunctional low dimensional nanomaterials are of great importance for in vivo imaging and safety therapy. Meanwhile, nanomaterials with good bio-compatible and effectively photothermal conversion are still demanded to be fabricated in biomedicine. In this work, we have developed two-dimensional bismuth selenide nanosheets as the imaging and photothermal nanoagents. Through doping engineering, the near infrared photothermal conversion of Nd doped nanosheets was boosted by 52 %, which is higher than many previous works. Besides, the prepared nanomaterials can realize infrared and in vivo computed X-ray tomography bioimaging, due to the rich optical-magnetic properties of Nd atoms. The in vitro and vivo experiments with mice display that the Nd doped nanosheets have low toxicity and high biocompatibility. More importantly, the nanomaterials can efficiently achieve photothermal tumor ablation. It is suggested that designed and developed nanosheets have promising applications for biomedicine.

Colon cancer, the third most frequent occurred cancer, has high mortality and extremely poor prognosis. Ginsenoside, the active components of traditional Chinese herbal medicine Panax ginseng, exerts antitumor effect in various cancers, including colon cancer. However, the detailed molecular mechanism of Ginsenoside in the tumor suppression have not been fully elucidated. Here, we chose the representative ginsenoside Rg3 and reported for the first time that Rg3 induces mitophagy in human colon cancer cells, which is responsible for its anticancer effect. Rg3 treatment leads to mitochondria damage and the formation of mitophagosome; when autophagy is inhibited, the clearance of damaged mitochondria can be reversed. Next, our results showed that Rg3 treatment activates the PINK1-Parkin signaling pathway and recruits Parkin and ubiquitin proteins to mitochondria to induce mitophagy. GO analysis of Parkin targets showed that Parkin interacts with a large number of mitochondrial proteins and regulates the molecular function of mitochondria. The cellular energy metabolism enzyme GAPDH is validated as a novel substrate of Parkin, which is ubiquitinated by Parkin. Moreover, GAPDH participates in the Rg3-induced mitophagy and regulates the translocation of Parkin to mitochondria. Functionally, Rg3 exerts the inhibitory effect through regulating the nonglycolytic activity of GAPDH, which could be associated with the cellular oxidative stress. Thus, our results revealed GAPDH ubiquitination by Parkin as a crucial mechanism for mitophagy induction that contributes to the tumor-suppressive function of ginsenoside, which could be a novel treatment strategy for colon cancer.

Morus alba is used as a traditional Chinese medicine due to its various biological activities. Phenylpropanoid metabolism is one of the most important pathways in Morus alba to produce secondary metabolites and response to stress. From the general phenylpropanoid pathway, there are two metabolic branches in M. alba, including flavonoid and lignin biosynthesis, which also play roles in response to stress. However, the dynamic changes between flavonoid and lignin biosynthesis under Botrytis cinerea infection and UV-B stress in M. alba were unclear. To explore the different regulation mode of flavonoid and lignin biosynthesis in M. alba leaves’ response to biotic and abiotic stress, a combined proteomic and metabolomic study of M. alba leaves under UV-B stress and B. cinerea infection was performed. The results showed that most of the proteins involved in the lignin and flavonoid biosynthesis pathway were increased under either UV-B stress or B. cinerea infection in M. alba. This was also confirmed by enzyme assays and metabolomics analysis. Additionally, the abundance of proteins involved in the biosynthesis of jasmonic acid was increased after B. cinerea infection. This suggests that both flavonoid and lignin biosynthesis participate in the responses to abiotic and biotic stress in M. alba, but they might be regulated by different hormone signaling.

Parkin, an E3 ubiquitin ligase, plays a role in maintaining mitochondrial homeostasis through targeting damaged mitochondria for mitophagy. Accumulating evidence suggests that the acetylation modification of the key mitophagy machinery influences mitophagy level, but the underlying mechanism is poorly understood. Here, our study demonstrated that inhibition of histone deacetylase (HDAC) by treatment of HDACis activates mitophagy through mediating Parkin acetylation, leading to inhibition of cervical cancer cell proliferation. Bioinformatics analysis shows that Parkin expression is inversely correlated with HDAC2 expression in human cervical cancer, indicating the low acetylation level of Parkin. Using mass spectrometry, Parkin is identified to interact with two upstream molecules, acetylase acetyl-CoA acetyltransferase 1 (ACAT1) and deacetylase HDAC2. Under treatment of suberoylanilide hydroxamic acid (SAHA), Parkin is acetylated at lysine residues 129, 220 and 349, located in different domains of Parkin protein. In in vitro experiments, combined mutation of Parkin largely attenuate the interaction of Parkin with PTEN induced putative kinase 1 (PINK1) and the function of Parkin in mitophagy induction and tumor suppression. In tumor xenografts, the expression of mutant Parkin impairs the tumor suppressive effect of Parkin and decreases the anticancer activity of SAHA. Our results reveal an acetylation-dependent regulatory mechanism governing Parkin in mitophagy and cervical carcinogenesis, which offers a new mitophagy modulation strategy for cancer therapy.

Drug resistance has become one of the largest challenges for cancer chemotherapies. Under certain conditions, cancer cells hijack autophagy to cope with therapeutic stress, which largely undermines the chemo-therapeutic efficacy. Currently, biomarkers indicative of autophagy-derived drug resistance remain largely inclusive. Here, we report a novel role of lipid rafts/cholesterol-enriched membrane micro-domains (CEMMs) in autophagosome biogenesis and doxorubicin resistance in breast tumors. We showed that CEMMs are required for the interaction of VAMP3 with syntaxin 6 (STX6, a cholesterol-binding SNARE protein). Upon disruption of CEMM, VAMP3 is released from STX6, resulting in the trafficking of ATG16L1-containing vesicles to recycling endosomes and subsequent autophagosome biogenesis. Furthermore, we found that CEMM marker CAV1 is decreased in breast cancer patients and that the CEMM deficiency-induced autophagy is related to doxorubicin resistance, which is overcome by autophagy inhibition. Taken together, we propose a novel model whereby CEMMs in recycling endosomes support the VAMP3 and STX6 interaction and function as barriers to limit the activity of VAMP3 in autophagic vesicle fusion, thus CEMM deficiency promotes autophagosome biogenesis and doxorubicin resistance in breast tumors.

The basic density (ρ), kinematic viscosity (v) and surface tension (γ) data of the 1,2-propanediol (1,2-PPD) (1) + 1,2-propane diamine (1,2-PDA) (2) binary system at T = (293.15, 298.15, 303.15, 308.15, 313.15 and 318.15) K were reported under atmospheric pressure (889 hectopascals in Hohhot, China). After that, the absolute viscosity (η), excess volume (VmE), viscosity deviation (Δη), surface tension difference (Δ γ), apparent molar volume (Vφ,1 and Vφ,2), partial molar volume (V1¯ and V2¯), isothermal expansion coefficient (αp) and excess Gibbs free energy (ΔG*E) of the binary system were further calculated. Meanwhile, the Redlich-Kister (R-K) equations were fitted to VmE, Δ η, and Δ γ values, and the corresponding equation coefficients were obtained to estimate the errors between the experimental and calculated values. Finally, the binary system was characterized by FTIR, UV-vis, FLS, 1H NMR, Raman spectroscopic techniques, and the bond energy and bond length between molecules were calculated by Gaussian 09 software to discuss the intermolecular interaction between 1,2-PPD and 1,2-PDA. The results show that hydrogen bonding interaction does exist among molecules in the form of -OH···N-. Herein, the work provides a basis for engineering design and also provides fundamental data for the application of the binary system.

Abstract Extreme torrential rainfall events are low‐probability events. A “China‐Record Extremely Heavy Rainfall” (CREHR) event with rain rate of 201.9 mm/hr occurred on 20 July in Zhengzhou in North China. Using high‐density meteorological observations, ERA5 reanalysis data, remote sensing data from China's FY‐4A satellite, and numerical simulation, we revealed that sufficient warm–humid airflows were continuously transported to the Zhengzhou area via multiple pathways that were mainly modulated by the large‐scale western Pacific subtropical high to the north along with the anomalies of the westerly belt and a meso‐scale binary typhoon system. At the local scale, under the combined action of the vertical circulation that caused low‐level convergence and high‐level divergence, and the rapid uplift of water vapor related to the blocking by mountainous terrain, this CREHR event was eventually triggered. Particularly, our present work shows the roles of both typhoon Cempaka and meso‐scale convective systems to south of Henan province can not be ignored, producing a strong super‐thick water vapor transport layer. The existence of the binary typhoon raises the level of uncertainty involved in the water vapor transport of this CREHR event.

Abstract Background Anatomic variation may increase the difficulty and risk of anatomic segmentectomy. The preoperative three-dimensional computed tomography bronchography and angiography (3D-CTBA) can provide a detailed model of the segmental structure, and contribute to precise and safe segmentectomy. Case presentation This is a case of anomalous bronchi and pulmonary vessels in the right upper posterior segment (RS2). Under the guidance of 3D-CTBA, anatomic RS2 segmentectomy was performed accurately and safely. The postoperative condition was uneventful. Conclusions This rare case highlights the importance of 3D-CTBA to guild accurate segmentectomy with anatomic variation.

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related mortality worldwide. Nowadays, liver-targeting drug delivery system has been proven as a promising strategy for overcoming HCC. Asialoglycoprotein receptor (ASGPR) is an ideal receptor for liver targeting, which is mainly expressed on hepatocytes. In this study, we developed several novel liver-targeting chitosan nanoparticles to selectively overcome HCC via ASGPR. Chitosan nanoparticles (Gly-CS-VE, Gal-Gly-CS-VE, Gly-CS-DCA, and Gal-Gly-CS-DCA) were prepared by grafting hydrophilic group (glycidol, Gly), hydrophobic group (deoxycholic acid, DCA or vitamin E succinate, VE), and ASGPR recognizing group (galactose, Gal). Subsequently, their characterizations were measured by 1H NMR, FT-IR, TEM, and DLS. Doxorubicin (DOX) was loaded in nanoparticles and released out in a pH-dependent manner. Most importantly, the galactosylated Gal-Gly-CS-VE and Gal-Gly-CS-DCA nanoparticles exhibited significantly stronger in vitro cell internalization, cytotoxicity, anti-migration capabilities and in vivo anticancer efficacies than the corresponding Gly-CS-VE and Gly-CS-DCA nanoparticles, as well as free DOX. Finally, the four chitosan nanoparticles exhibited good biocompatibility without causing any obvious histological damage to the major organs. Overall, the galactosylated chitosan nanoparticles were proven to be promising pharmaceutical formulations for selectively overcoming HCC, with great potential for clinical applications.

Biomineralization is a common phenomenon in nature, and organisms can prepare functional materials with multi-level ordered structures through biomineralization. Herein, inspired by biomineralization, for the first time, we developed an amino acid quantum dots (ACDs)–CO2-Ca(OH)2 system to study the biomineralization process of CaCO3 in the presence of ACDs. The ACDs could not only control the morphology and crystal form of CaCO3 but also could be doped into CaCO3 during the formation of CaCO3 to form ACDs@CaCO3 organic–inorganic hybrid fluorescent materials which had excellent luminous ability. Meanwhile, the morphology and crystal form of CaCO3 could also be controlled by controlling the CO2 flow rate and rotation speed. After that, a possible biomineralization mechanism of CaCO3 in the presence of ACDs was proposed. Finally, the synthetic spherical ACDs@CaCO3 were applied to the field of biological imaging for the first time. Our work not only provides new bionic methods for the synthesis of multifunctional biomineralized materials and new insights for further understanding of biomineralization mechanism, but also the synthesized new biomineralization fluorescent materials have great application potential in the field of bioimaging.