Effects of Recombinant Human Granulocyte/Macrophage Colony-Stimulating Factor on Diabetic Lower Extremity Ulcers: Case Series of Nine Patients.

Background: Diabetic lower extremity ulcer, including diabetic foot ulcer (DFU) and leg ulcer, is one of the refractory complications of diabetes, the treatment of which is challenging, expensive, and lengthy. Recombinant Human Granulocyte/Macrophage Colony-stimulating Factor (rhGM-CSF) is an immunomodulatory cytokine that has been mainly applied in the treatment of hematological diseases. Clinical evidence regarding GM-CSF in the treatment of diabetic lower extremity ulcers is limited. This study is the first case series that investigates the repurpose effects of rhGM-CSF on diabetic ulcer healing in real clinical practice. Methods: Nine patients diagnosed with diabetes and refractory lower extremity ulcer (ulcer duration ≥2 weeks) were included from September 2021 to February 2023 in the Division of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Patients with Wagner grade ≥4 and SINDAD ≥5 were excluded. The included subjects were treated with rhGM-CSF plus standard of care (SOC) including glycemic control, foot care education, debridement of necrotic tissues, topical wound dressings, offloading, and infection control when necessary. The observation endpoint was complete epithelialization. Their clinical manifestations, laboratory tests, and therapeutic effects were extracted and analyzed. Results: The case series included 9 cases aged from 29 to 80 years and all the patients were male. Seven of 9 patients presented neuropathic ulcer. Only one case showed non-infected ulcer from tissue samples and one case presented ankle brachial index (ABI) <0.9. It was observed that the ulcer areas among these 9 patients gradually declined throughout the whole treatment period with the average healing velocity 0.32 ± 013 cm2/day and the mean time to complete healing 16.0 ± 3.7 days. The relative area (percentage of initial ulcer area) decreased to 66.7 ± 13.0% on average after the first treatment. Ulcers in all the 9 patients achieved complete epithelialization after 4-8 times treatments. Conclusion: The case series suggests rhGM-CSF as a promising therapeutic strategy for the treatment of diabetic ulceration. More robust data from randomized controlled trials are required to further evaluate its clinical efficacy.

Electroacupuncture regulates Rab5a-mediating NGF transduction to improve learning and memory ability in the early stage of AD mice.

AIMS: Nerve growth factor (NGF) loss is a potential factor for the degeneration of basal forebrain cholinergic neurons (BFCNs) in Alzheimer's disease (AD), and Rab5a is a key regulatory molecule of NGF signaling transduction. Here, we investigated the changes of Rab5a in 5 × FAD mice and further explored the mechanism of Electroacupuncture (EA) treatment in improving cognition in the early stage of AD. METHODS: The total Rab5a and Rab5a-GTP in 5-month-old 5 × FAD mice and wild-type mice were detected using WB and IP technologies. 5 × FAD mice were treated with EA at the Bai hui (DU20) and Shen ting (DU24) acupoints for 4 weeks and CRE/LOXP technology was used to confirm the role of Rab5a in AD mediated by EA stimulation. The Novel Object Recognition and Morris water maze tests were used to evaluate the cognitive function of 5 × FAD mice. The Nissl, immunohistochemistry, and Thioflavin S staining were used to observe pathological morphological changes in the basal forebrain circuit. The Golgi staining was used to investigate the synaptic plasticity of the basal forebrain circuit and WB technology was used to detect the expression levels of cholinergic-related and NGF signal-related proteins. RESULTS: The total Rab5a was unaltered, but Rab5a-GTP increased and the rab5a-positive early endosomes appeared enlarged in the hippocampus of 5 × FAD mice. Notably, EA reduced Rab5a-GTP in the hippocampus in the early stage of 5 × FAD mice. EA could improve object recognition memory and spatial learning memory by reducing Rab5a activity in the early stage of 5 × FAD mice. Moreover, EA could reduce Rab5a activity to increase NGF transduction and increase the levels of phosphorylated TrkA, AKT, and ERK in the basal forebrain and hippocampus, and increase the expression of cholinergic-related proteins, such as ChAT, vAchT, ChT1, m1AchR, and m2AchR in the basal forebrain and ChAT, m1AchR, and m2AchR in the hippocampus, improving synaptic plasticity in the basal forebrain hippocampal circuit in the early stage of 5 × FAD mice. CONCLUSIONS: Rab5a hyperactivation is an early pathological manifestation of 5 × FAD mice. EA could suppress Rab5a-GTP to promote the transduction of NGF signaling, and enhance the synaptic plasticity of the basal forebrain hippocampal circuit improving cognitive impairment in the early stage of 5 × FAD mice.

The fate of plastic wraps in constructed wetland: Surface structure and microbial community.

The high use of plastic wraps leads to significant environmental pollution. In this study, the surface structure and microbial community evolution of commercially available plastic wraps [polyethylene (PE), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), and polylactic acid (PLA)] in constructed wetlands (CWs) were investigated. The results indicated that all plastic wraps gradually decreased in molecular weight, crystallinity, melting, and crystallization temperatures, whereas a gradual increase was observed in the surface roughness, polymer dispersity index (PDI), carbonyl index (CI) and Shannon index of microorganisms colonizing the CWs. The aging rate of the plastic wrap was in the order: PLA > PVC > PE > PVDC, at the same site in the CWs, and it was in the order: soil surface > plant roots > subsoil, for the same plastic wrap. The diversity of microorganisms colonizing the same plastic wrap was in the order: plant roots > subsoil > soil surface. The Shannon indices of microorganisms on plastic wraps were lower than those in the soil, indicating that the diversity of microorganisms colonizing plastic wraps is limited. Additionally, the microbial community structure on the plastic surface was co-differentiated by the plastic type, placement position in the CWs, and aging time. Significantly different microbial community structures were found on the PVC and PVDC wrap surfaces, revealing that the chlorine in plastics limits microbial diversity. Unclassified members of Rhizobiaceae and Pseudomonadaceae were the dominant genera on the surface of the plastic wraps, suggesting that they may be the microorganisms involved in plastic degradation processes. The study provides valuable perspectives to facilitate a comprehensive understanding of the migration, fate, and environmental risks associated with microplastics (MPs) in wetlands.

Differential Gene Analysis of Langerhans Cell Histiocytosis and the Significance of MMP1-Targeted Drug Repositioning.

Langerhans cell histiocytosis (LCH) is a rare condition predominantly affecting young children. Activation of the MAPK pathway has offered key new insights into the pathogenesis of LCH; however, the precise mechanisms underlying its occurrence and development are still far from being completely elucidated. There is still a relapse/reactivation rate in patients with multisystem LCH. Therefore, this study aimed to investigate other potential LCH pathophysiologies and prospective therapeutic targets. The gene expression omnibus (GEO) database was used to retrieve gene expression profiles of LCH (GSE16395). Three distinct types of analyses were performed after identifying the common differentially expressed genes (DEGs) in LCH: hub gene identification, functional annotation, module construction, drug repositioning, and expression analysis via immunohistochemistry (IHC). We identified 417 common DEGs and 50 central hub genes. This functional study highlighted the significance of keratinization, skin development, and inflammation. In addition, we predicted new drug candidates (RS2 drugs targeting matrix metalloprotease1, MMP1) that could be used for LCH treatment. Finally, gene-miRNA and gene-TF networks and immune cell infiltration were analyzed for MMP1-related genes. MMP1 expression levels in LCH tissues were validated by IHC. Our study identified the central communal genes and novel drug candidates. These shared pathways and hub genes offer new perspectives on future mechanisms of action and therapeutic targets.

Suppression of AGRN enhances CD8+ T cell recruitment and inhibits breast cancer progression.

Breast cancer (BC) stands as a prominent contributor to global cancer-related mortality, with an increasing incidence annually. This study aims to investigate AGRN gene expression in BC, as well as explore its influence on the tumor immune microenvironment. AGRN displayed a pronounced upregulation in BC tissues relative to paracancerous tissues. Single-cell RNA analysis highlighted AGRN-specific elevation within cancer cell clusters and also showed expression expressed in stromal as well as immune cell clusters. AGRN upregulation was positively correlated with clinicopathological stage and negatively correlated with BC prognosis. As revealed by the in vitro experiment, AGRN knockdown effectively hinders BC cells in terms of proliferation, invasion as well as migration. AGRN protein, which may interact with EXT1, LRP4, RAPSN, etc., was primarily distributed in the cell cytoplasm. Notably, immune factors might interact with AGRN in BC, evidenced by its discernible associations with immunofactors like IL10, CD274, and PVRL2. Mass spectrometry and immunohistochemistry revealed that the reduction of AGRN led to an increase in CD8+ T cells with triple-negative breast cancer (TNBC). Mechanistically, the connection between TRIM7 and PD-L1 is improved by AGRN, acting as a scaffold, thereby facilitating the accelerated degradation of PD-L1 by TRIM7. Downregulation of AGRN inhibits BC progression and increases CD8+ T cell recruitment. Targeting AGRN may contribute to BC treatment. The biomarker AGRN, serving as a therapeutic target for BC, emerges as a prospective avenue for enhancing both diagnosis and prognosis in BC cases.

[Astragali Radix-Curcumae Rhizoma inhibits colon cancer progression and enhances 5-FU efficacy by regulating hypoxia-inducible factors and tumor stem cells].

The animal and cell models were used in this study to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in inhibiting colon cancer progression and enhancing the efficacy of 5-fluorouracil(5-FU) by regulating hypoxia-inducible factors and tumor stem cells. The animal model was established by subcutaneous transplantation of colon cancer HCT116 cells in nude mice, and 24 successfully modeled mice were randomized into model, 5-FU, HQEZ, and 5-FU+HQEZ groups. The tumor volume was measured every two days. Western blot was employed to measure the protein levels of epidermal growth factor receptor(EGFR), dihydropyrimidine dehydrogenase(DPYD), and thymidylate synthase(TYMS), the key targets of the hypoxic core region, as well as the hypoxia-inducible factors HIF-1α and HIF-2α and the cancer stem cell surface marker CD133 and SRY-box transcription factor 2(SOX2). The results of animal experiments showed that HQEZ slowed down the tumor growth and significantly increased the tumor inhibition rate of 5-FU. Compared with the model group, HQEZ significantly down-regulated the protein levels of EGFR and DPYD, and 5-FU+HQEZ significantly down-regulated the protein levels of EGFR and TYMS in tumors. Compared with the model group, HQEZ significantly down-regulated the protein levels of HIF-1α, HIF-2α, SOX2, and CD133 in the hypoxic core region. Compared with the 5-FU group, 5-FU+HQEZ lowered the protein levels of HIF-1α, HIF-2α, and SOX2. The cell experiments showed that the protein le-vels of HIF-1α and HIF-2α in HCT116 cells elevated significantly after low oxygen treatment. Compared with 5-FU(1.38 µmol·L~(-1)) alone, HQEZ(40 mg·mL~(-1)) and 5-FU+HQEZ significantly down-regulated the protein levels of HIF-1α, HIF-2α, and TYMS. In conclusion, HQEZ can inhibit the expression of hypoxia-responsive molecules in colon cancer cells and reduce the properties of cancer stem cells, thereby enhancing the therapeutic effect of 5-FU on colon cancer.

Landscape of transcriptome-wide m6A modification in diabetic liver reveals rewiring of PI3K-Akt signaling after physical exercise.

AIM: Type 2 diabetes mellitus (T2DM) is one of the most common diseases, and epigenetic modification N6-methyladenosine (m6A) is essential for transcriptional modulation involved in its development. However, the precise role and landscape of transcriptome-wide m6A alterations in molecular adaptations after physical exercise have yet to be fully elucidated. METHODS: Four-week-old male C57BL/6J mice received a high-fat diet (HFD) for 12 weeks to establish a diabetic state, and HFD mice were simultaneously subjected to physical exercise (HFD + EX). The hepatic RNA m6A methylome was examined, the conjoint MeRIP-seq and RNA-seq was performed, and the exercise-modulated genes were confirmed. RESULTS: Physical exercise significantly ameliorates liver metabolic disorder and triggers a dynamic change in hepatic RNA m6A. By analyzing the distribution of m6A in transcriptomes, an abundance of m6A throughout mRNA transcripts and a pattern of conserved m6A after physical exercise was identified. It is noteworthy that conjoint MeRIP-seq and RNA-seq data revealed that both differentially methylated genes and differentially expressed genes were enriched in all stages of the PI3K-Akt signaling pathway, in particular the upstream nodes of this pathway, which are considered a valuable therapeutic target for T2DM. Moreover, in vivo and in vitro analyses showed that exercise-mediated methyltransferase Rbm15 positively regulated the expression of two upstream genes (Itga3 and Fgf21) in an m6A-dependent manner. CONCLUSION: These findings highlight the pivotal role of the exercise-induced m6A epigenetic network and contribute insights into the intricate epigenetic mechanism underlying insulin signaling.

Trunk kinematic analysis of ascent and descent stairs in college students with idiopathic scoliosis: a case-control study.

BACKGROUND CONTEXT: Traditional 3D motion analysis typically considers the spine as a rigid entity. Nevertheless, previous single-joint models have proven inadequate in evaluating the movement across different spinal segments in patients with idiopathic scoliosis (IS). Scoliosis significantly impairs movement functions, especially during activities such as ascending and descending stairs. There is a lack of research on the patterns of stair movement specifically for patients with IS. PURPOSE: This study aims to investigate trunk kinematics in college students with IS during stair ascent and descent tasks. A total of 56 participants, 28 with IS and 28 with healthy controls, were recruited for this case-control study. The trunk movements were analyzed using a motion analysis system that incorporated a multisegment spine model. Understanding the multi-segment spine kinematics during stair tasks can contribute to the development of effective rehabilitation programs for individuals with IS. STUDY DESIGN: Case-control study. SAMPLE SIZE: 28 IS and 28 controls. OUTCOME MEASURES: Cobb angle, spinal curvature, spinal active range of motion (ROM), Kinematics METHODS: The Qualisys system (Gothenburg, Sweden) was utilized in this study with a sampling frequency of 150 Hz. It recorded the kinematics in the thoracic, lumbar, thoracic cage, and pelvis while ascending and descending stairs for both the 28 IS individuals and the 28 control participants. Additionally, clinical parameters such as the Cobb angle, curvature of the spine, spinal range of motion (ROM), and other relevant factors were concurrently assessed among the subjects. Project supported by the National Natural Science Foundation of China (Grant No. 82205306). The authors declare no conflict of interest in preparing this article. RESULTS: The findings of this study revealed that IS individuals exhibited reduced kyphotic curvature in the sagittal plane (p<.05) when compared to the control group. In contrast, these IS patients displayed greater coronal curvature (Cobb angle) in the frontal plane and a more substantial difference in thoracic side bending range of motion in comparison to the control group (p.05). Moreover, during the ascending stair activity, IS patients showed reduced thoracic cage flexion-extension range of motion (p<.05), while displaying increased lumbar rotation range of motion and anterior-posterior pelvic tilt range of motion (p<.05) in contrast to the control group. Notably, the kinematic analysis during the descent of stairs indicated that IS patients exhibited a larger range of motion in thoracic flexion-extension, thoracic side bending, thoracic cage side bending, thoracic rotation, and thoracic cage rotation when compared to the control group (p<.05). CONCLUSIONS: The results showed significant differences in trunk kinematics between the two groups during both stair ascent and descent tasks. The utilization of the "multisegment spine model" facilitates the acquisition of motion information across multiple segments of the spine in patients diagnosed with IS, effectively enhancing the assessment outcomes derived from imaging information. The three-dimensional structural deformity in the trunk affects both static and dynamic activity patterns. In different activity states, IS patients demonstrate stiff movements in certain segments while experiencing compensatory instability in others. In the future, clinical rehabilitation programs for IS should prioritize stair-related activity training.

Impact of Delirium Onset and Duration on Mortality in Patients With Cancer Admitted to the ICU.

BACKGROUND: Little is known on the effects of delirium onset and duration on outcome in critically ill patients with cancer. OBJECTIVES: To determine the impact of delirium onset and duration on intensive care unit (ICU) and hospital mortality and length of stay (LOS) in patients with cancer. METHODS: Of the 915 ICU patients admitted in 2018, 371 were included for analysis after excluding for terminal disease, <24-h ICU stay, lack of active cancer and delirium. Delirium was defined as early if onset was within 2 days of ICU admission, late if onset was on day 3 or later, short if duration was 2 days or less, and long if duration was 3 days or longer. Patients were placed into 4 combination groups: early-short, early-long, late-short, and late-long delirium. Multivariate analysis controlling for sex, age, metastatic disease, and predelirium hospital LOS was performed to determine ICU and hospital mortality and LOS. Exploratory analysis of long-term survival was also performed. Restricted cubic splines were performed to confirm the use of 2 days to distinguish between early versus late onset and short versus long duration. RESULTS: A total of 32.9% (n = 122) patients had early-short, 39.1% (n = 145) early-long, 16.2% (n = 60) late-short, and 11.9% (n = 44) late-long delirium. Late-long delirium was independently associated with increased ICU (OR 4.45, CI 1.92-10.30; P < .001) and hospital (OR 2.91, CI 1.37-6.19; P = .005) mortality and longer ICU (OR 1.97, CI 1.58-2.47; P < .001) LOS compared to early-short delirium. Early delirium had better overall survival at 18 months than late delirium. Long-term survival further improved when delirium duration was 2 days or less. Prediction heatmaps confirm the use of a 2-day cutoff. CONCLUSION: Late delirium, especially with long duration, significantly worsens outcome in ICU patients with cancer and should be considered a harbinger of poor overall condition.

Detection and Recognition of the Invasive species, Hylurgus ligniperda, in Traps, Based on a Cascaded Convolution Neural Network.

BACKGROUND: Hylurgus ligniperda, an invasive species originating from Eurasia, is now a major forestry quarantine pest worldwide. In recent years, it has caused significant damage in China. While traps have been effective in monitoring and controlling pests, manual inspections are labor-intensive and require expertise in insect classification. To address this, we applied a two-stage cascade convolutional neural network, YOLOX-MobileNetV2 (YOLOX-Mnet), for identifying H. ligniperda and other pests captured in traps. This method streamlines target and non-target insect detection from trap images, offering a more efficient alternative to manual inspections. RESULTS: Two cascade convolutional neural network models were employed in two stages to detect both target and non-target insects from images captured in the same forest. Initially, You Only Look Once X (YOLOX) served as the target detection model, identifying insects and non-insects from the collected images, with non-insect targets subsequently filtered out. In the second stage, MobileNetV2, a classification network, classified the captured insects. This approach effectively reduced false positives from non-insect objects, enabled the inclusion of additional classification terms for multi-class insect classification models, and utilized sample control strategies to enhance classification performance. CONCLUSION: Application of the cascade convolutional neural network model accurately identified H. ligniperda, and Mean F1-score of all kinds of insects in the trap was 0.98. Compared to traditional insect classification, this method offers great improvement in the identification and early warning of forest pests, as well as provide technical support for the early prevention and control of forest pests. This article is protected by copyright. All rights reserved.

Reference Standards of Cardiorespiratory Fitness Measured With the Cardiopulmonary Exercise Test Using the Treadmill in Chinese Adults Younger Than 60 Years.

PURPOSE: Cardiorespiratory fitness (CRF) is a strong predictor of cardiorespiratory diseases and varies by race. The purpose of this study was to provide CRF reference standards and a prediction equation for peak oxygen uptake (V˙O 2peak ) from treadmill-based cardiopulmonary exercise testing (CPX) in Chinese individuals. METHODS: Healthy participants (n = 4199) who completed a CPX using a treadmill were studied. The percentiles of V˙O 2peak were determined for four age groups (decades). A regression prediction model was developed from the derivation cohort (n = 3361), validated in the independent validation cohort (n = 838), and compared with the widely used Wasserman equation and the Fitness Registry and the Importance of Exercise National Database (FRIEND) equation. RESULTS: The mean V˙O 2peak values of four age groups (20-29, 30-39, 40-49, and 50-59 yr) were 42.6, 41.2, 38.7, and 35.9 mL/kg/min, respectively, for men, and 37.1, 34.7, 32.0, and 30.3 mL/kg/min, respectively, for women. The 50th percentiles of relative V˙O 2peak decreased with age for both sexes. The prediction equation was: Absolute V˙O 2peak (mL/min) = 236.68 - (504.64 × sex [male = 0; female = 1]) + (21.23× weight [kg]) - (14.31 × age [yr]) + (9.46 × height [cm]) (standard error of the estimate = 379.59 mL/min, R2 = 0.66, P < .001).Percentage predicted V˙O 2peak for the validation sample was 100.2%. The novel equation performed better than the other two equations. CONCLUSION: This study reports the first CRF reference standards and prediction equation generated from treadmill CPX in China. These reference standards provide a framework for interpreting the CRF of the Chinese population and could be useful information for a global CRF database.

Robust Superhydrophobic Composite Fabric with Self-Healing and Chemical Durability.

Superhydrophobic fabrics with multiple functions have become a research hotspot. However, it is challenging to make self-healing mechanically robust and eco-friendly superhydrophobic fabrics, which are limited by complex fabrication processes and excessive use of environmentally unfriendly solvents during fabrication. Herein, inspired by the secretion of a waxy substance from the surface of lotus leaves to restore water repellency, self-healing superhydrophobic composite fabrics (as-synthesized PA66/6-PET@Tico) are obtained by constructing a papillary TiO2 and tentacle-like fluorinated acrylate polymer (FCB015) coating on polyester-nylon composite fabrics using two-step hydrothermal method. The result indicates that PA66/6-PET@Tico with hierarchical micro/nanostructure exhibits excellent superhydrophobic and self-healing properties. Compared with FCB015 coated fabric, the contact angles (CA) of water and soybean oil rise to 172.2° and 166.8° from 137.4° and 98.8°, respectively. After mechanical abrasion, PA66/6-PET@Tico recovers a water contact angle (WCA) of 165.6° at room temperature. The WCA remains higher than 155° after 18 h of chemical corrosion. Furthermore, the bacterial inhibition rates of PA66/6-PET@Tico for Staphylococcus Aureus and Escherichia Coli are 99.90 and 98.38%, respectively. In this work, a new idea is proposed for designing a simple and effective self-healing superhydrophobic coating, expecting to promote the large-scale industrial production and application of functional surfaces.

Elevation-dependent pattern of net CO2 uptake across China.

The elevation gradient has long been known to be vital in shaping the structure and function of terrestrial ecosystems, but little is known about the elevation-dependent pattern of net CO2 uptake, denoted by net ecosystem productivity (NEP). Here, by analyzing data from 203 eddy covariance sites across China, we report a negative linear elevation-dependent pattern of NEP, collectively shaped by varying hydrothermal factors, nutrient supply, and ecosystem types. Furthermore, the NEP shows a higher temperature sensitivity in high-elevation environments (3000-5000 m) compared with the lower-elevation environments (<3000 m). Model ensemble and satellite-based observations consistently reveal more rapid relative changes in NEP in high-elevation environments during the last four decades. Machine learning also predicts a stronger relative increase in high-elevation environments, whereas less change is expected at lower elevations. We therefore conclude a varying elevation-dependent pattern of the NEP of terrestrial ecosystems in China, although there is significant uncertainty involved.

Functional and Compositional Changes in Sirex noctilio Gut Microbiome in Different Habitats: Unraveling the Complexity of Invasive Adaptation.

The mutualistic symbiosis relationship between the gut microbiome and their insect hosts has attracted much scientific attention. The native woodwasp, Sirex nitobei, and the invasive European woodwasp, Sirex noctilio, are two pests that infest pines in northeastern China. Following its encounter with the native species, however, there is a lack of research on whether the gut microbiome of S. noctilio changed, what causes contributed to these alterations, and whether these changes were more conducive to invasive colonization. We used high-throughput and metatranscriptomic sequencing to investigate S. noctilio larval gut and frass from four sites where only S. noctilio and both two Sirex species and investigated the effects of environmental factors, biological interactions, and ecological processes on S. noctilio gut microbial community assembly. Amplicon sequencing of two Sirex species revealed differential patterns of bacterial and fungal composition and functional prediction. S. noctilio larval gut bacterial and fungal diversity was essentially higher in coexistence sites than in separate existence sites, and most of the larval gut bacterial and fungal community functional predictions were significantly different as well. Moreover, temperature and precipitation positively correlate with most of the highly abundant bacterial and fungal genera. Source-tracking analysis showed that S. noctilio larvae at coexistence sites remain dependent on adult gut transmission (vertical transmission) or recruitment to frass (horizontal transmission). Meanwhile, stochastic processes of drift and dispersal limitation also have important impacts on the assembly of S. noctilio larval gut microbiome, especially at coexistence sites. In summary, our results reveal the potential role of changes in S. noctilio larval gut microbiome in the successful colonization and better adaptation of the environment.

Hierarchically Responsive Alternating Nano-Copolymers with Tailored Interparticle Bonds.

Self-assembly of inorganic nanoparticles (NPs) is an essential tool for constructing structured materials with a wide range of applications. However, achieving ordered assembly structures with externally programmable properties in binary NP systems remains challenging. In this work, we assemble binary inorganic NPs into hierarchically pH-responsive alternating copolymer-like nanostructures in an aqueous medium by engineering the interparticle electrostatic interactions. The polymer-grafted NPs bearing opposite charges are viewed as nanoscale monomers ("nanomers"), and copolymerized into alternating nano-copolymers (ANCPs) driven by the formation of interparticle "bonds" between nanomers. The resulting ANCPs exhibit reversibly responsive "bond" length (i.e., the distance between nanomers) in response to the variation of pH in a range of ~7-10, allowing precise control over the surface plasmon resonance of ANCPs. Moreover, specific interparticle "bonds" can break up at pH≥11, leading to the dis-assembly of ANCPs into molecule-like dimers and trimers. These dimeric and trimeric structures can reassemble to form ANCPs owing to the resuming of interparticle "bonds", when the pH value of the solution changes from 11 to 7. The hierarchically responsive nanostructures may find applications in such as biosensing, optical waveguide, and electronic devices.

A nano-platform combats the "attack" and "defense" of cytoskeleton to block cascading tumor metastasis.

The cytoskeleton facilitates tumor cells invasion into the bloodstream via vasculogenic mimicry (VM) for "attack", and protects cells against external threats through cytoskeletal remodeling and tunneling nanotubes (TNTs) for "defense". However, the existing strategies involving cytoskeleton are not sufficient to eliminate tumor metastasis due to mitochondrial energy supply, both within tumor cells and from outside microenvironment. Here, considering the close relationship between cytoskeleton and mitochondria both in location and function, we construct a nano-platform that combats the "attack" and "defense" of cytoskeleton in the cascading metastasis. The nano-platform is composed of KFCsk@LIP and KTMito@LIP for the cytoskeletal collapse and mitochondrial dysfunction. KFCsk@LIP prevents the initiation and circulation of cascading tumor metastasis, but arouses limited suppression in tumor cell proliferation. KTMito@LIP impairs mitochondria to trigger apoptosis and impede energy supply both from inside and outside, leading to an amplified effect for metastasis suppression. Further mechanisms studies reveal that the formation of VM and TNTs are seriously obstructed. Both in situ and circulating tumor cells are disabled. Subsequently, the broken metastasis cascade results in a remarkable anti-metastasis effect. Collectively, based on the nano-platform, the cytoskeletal collapse with synchronous mitochondrial dysfunction provides a potential therapeutic strategy for cascading tumor metastasis suppression.

MTIE-Net: Multi-technology fusion of low-light image enhancement network.

Images obtained in low-light scenes are often accompanied by problems such as low visibility, blurred details, and color distortion, enhancing them can effectively improve the visual effect and provide favorable conditions for advanced visual tasks. In this study, we propose a Multi-Technology Fusion of Low-light Image Enhancement Network (MTIE-Net) that modularizes the enhancement task. MTIE-Net consists of a residual dense decomposition network (RDD-Net) based on Retinex theory, an encoder-decoder denoising network (EDD-Net), and a parallel mixed attention-based self-calibrated illumination enhancement network (PCE-Net). The low-light image is first decomposed by RDD-Net into a lighting map and reflectance map; EDD-Net is used to process noise in the reflectance map; Finally, the lighting map is fused with the denoised reflectance map as an input to PCE-Net, using the Fourier transform for illumination enhancement and detail recovery in the frequency domain. Numerous experimental results show that MTIE-Net outperforms the comparison methods in terms of image visual quality enhancement improvement, denoising, and detail recovery. The application in nighttime face detection also fully demonstrates its promise as a pre-processing means in practical applications.

Association of maternal phthalates exposure and metabolic gene polymorphisms with congenital heart diseases: a multicenter case-control study.

BACKGROUND: The majority of congenital heart diseases (CHDs) are thought to result from the interactions of genetics and the environment factors. This study aimed to assess the association of maternal non-occupational phthalates exposure, metabolic gene polymorphisms and their interactions with risk of CHDs in offspring. METHODS: A multicenter case-control study of 245 mothers with CHDs infants and 268 control mothers of health infant was conducted from six hospitals. Maternal urinary concentrations of eight phthalate metabolites were measured by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Twenty single nucleotide polymorphisms (SNPs) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and 19 (CYP2C19), uridine diphosphate (UDP) glucuronosyl transferase family 1 member A7 (UGT1A7), family 2 member B7 (UGT2B7) and B15(UGT2B15) genes were genotyped. The multivariate logistic regressions were used to estimate the association between maternal phthalates exposure or gene polymorphisms and risk of CHDs. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene and gene-phthalates exposure interactions. RESULTS: There was no significant difference in phthalate metabolites concentrations between the cases and controls. No significant positive associations were observed between maternal exposure to phthalates and CHDs. The SNPs of UGT1A7 gene at rs4124874 (under three models, log-additive: aOR = 1.74, 95% CI:1.28-2.37; dominant: aOR = 1.86, 95% CI:1.25-2.78; recessive: aOR = 2.50, 95% CI: 1.26-4.94) and rs887829 (under the recessive model: aOR = 13.66, 95% CI: 1.54-121) were significantly associated with an increased risk of CHDs. Furthermore, the associations between rs4124874 (under log-additive and dominant models) of UGT1A7 were statistically significant after the false discovery rate correction. No significant gene-gene or gene-phthalate metabolites interactions were observed. CONCLUSIONS: The polymorphisms of maternal UGT1A7 gene at rs4124874 and rs887829 were significantly associated with an increased risk of CHDs. More large-scale studies or prospective study designs are needed to confirm or refute our findings in the future.

Bilayer fiber membrane electrospun from polylactic acid/alginate/bromelain and polylactic acid for enhancing the functionality of tea bags.

Tea bags have been extensively used in the food industry and daily life as an efficient way to pack tea. However, the large pores of the commercial tea bags not only lead to the inner contents of tea bag susceptible to bacteria and moisture but also result in the faster water infusion which is undesired during tea brewing. In this study, the polylactic acid (PLA)-PLA/sodium alginate (SA)/bromelain (BL) bilayer fiber membrane imitating the asymmetric wetting structure of lotus leaf blades was fabricated to avoid the above disadvantages of commercial tea bag. The PLA/SA/BL skin-core nanofiber membrane which imitating the skin-core structure of lotus leaf stems was first prepared as the hydrophilic and support layer, then a hydrophobic PLA layer was deposited on top via electrospinning. The PLA-PLA/SA/BL bilayer fiber membrane had a breaking strength of 5.5 MPa and started to decompose at 260 °C. Using this bilayer membrane, tea bags were designed with a novel structure where the hydrophobic PLA layer was placed in the same direction. The novel structure endow the those tea bags a slow and directional water transfer property. Therefore, the PLA-PLA/SA/BL bilayer fiber membrane has great potential for applications as tea bags.

A core-shell AuNRs@BUT-16 nanocomposite for enhancement SERS detection and efficient removal of deoxynivalenol.

INTRODUCTION: Deoxynivalenol (DON) is widely found in grains and poses a serious threat to human health, so there is an urgent need to develop methods for its simultaneous removal and detection. The novel metal organic framework (MOF) material BUT-16 has a high adsorption capacity (79.8%) for DON. Meanwhile, surface-enhanced Raman spectroscopy (SERS) has been widely used for rapid detection of analytes. OBJECTIVES: The aim of this work is to prepare a material that can be used for enhancement SERS detection and efficient removal of DON. METHODS: AuNRs@BUT-16 was prepared by in-situ solvothermal method and characterized using a series of characterization tools. AuNRs@BUT-16 was used as an adsorbent and SERS substrate for the removal and detection of DON, and some factors affecting the adsorption and SERS detection were investigated. The adsorption mechanism between DON and AuNRs@BUT-16 was investigated using molecular docking. The proposed SERS method was used to detect DON contamination in real samples. RESULTS: The prepared core-shell AuNRs@BUT-16 showed a synergistic effect in improving DON adsorption and SERS response. 97.6 % of DON was removed by AuNRs@BUT-16 in aqueous solution, and 70 % in 80 % methanol. The pre-enrichment effect of BUT-16 could trap more DON molecules in the "hot spots" of AuNRs, thus the proposed SERS sensor based on AuNRs@BUT-16 substrate displayed outstanding SERS response and the limit of detection of DON was 3.87 × 10-3 µg/mL. Molecular docking revealed that hydrogen bond and π-alkyl interaction were the main reasons for high affinity between BUT-16 and DON, and Au-O bonds facilitated the adsorption of DON on AuNRs. CONCLUSIONS: AuNRs@BUT-16 with superior enrichment and SERS detection capabilities has been used for simultaneous removal and SERS detection of DON, and it also has great potential to realize sensitive and selective detection and removal of DON in multiple disciplines.