Development of a bioluminescent immunoassay based on Fc-specific conjugated antibody-nanoluciferase immunoreagents for determining aflatoxin B1.

Aflatoxin B1 (AFB1) is a potent carcinogen, and is among the most hazardous mycotoxins in agricultural products. Therefore, the development of sensitive and convenient detection methods for AFB1 is significant for food safety against mycotoxins. Herein, a bioluminescent enzyme immunoassay (BLEIA) was developed for ultrasensitive detection of AFB1, based on the novel Fc-specific antibody-nanoluciferase (Ab-Nluc) conjugates which were fabricated using an IgG-binding protein-assisted photo-conjugation strategy. In indirect competitive immunoassay format, the proposed BLEIA exhibited the detection limit of 0.0232 ng mL-1, which was 37.4-fold lower than that obtained using the classical enzyme-linked immunosorbent assay (ELISA) based on Ab-horseradish peroxidase (Ab-HRP) chemical conjugates (0.868 ng mL-1). Meanwhile, the BLEIA exhibited high accuracy and precision. Thus, the proposed Fc-specific Ab-Nluc conjugates-based BLEIA provides an ultrasensitive and reliable method for detecting toxins and has potential for use in food safety monitoring.

Ginsenoside Rg2 alleviates astrocyte inflammation and ameliorates the permeability of the Alzheimer's disease related blood-brain barrier.

BACKGROUND: Damage to the blood-brain barrier (BBB) is vital for the development of Alzheimer's disease (AD). Ginsenoside Rg2 (G-Rg2) has been shown to improve a variety of brain injuries, but whether G-Rg2 can improve the BBB leakage related to AD is still unclear. PURPOSE: Illuminate the effect and mechanism of G-Rg2 on AD-related BBB damage. To clarify the role of G-Rg2 in Toll-like receptor pathway and oxidative stress pathway and its effect on tight junction proteins (TJs) expression in vivo and in vitro experiments. METHODS AND RESULTS: In our research, the tightness of the BBB was improved and the inflammatory pathway was suppressed after 4 weeks of treatment with G-Rg2 (10 mg kg-1 and 20 mg kg-1) in aluminum trichloride (AlCl3) plus d-galactose (D-gal) caused AD mice (p < 0.05; p < 0.01). Concurrently, the stability of TJs in mouse brain endothelial cells (bEnd3) was improved after okadaic acid (OA) -induced AD model cells were pretreated with G-Rg2 (5 µM, 10 µM, and 20 µM) for 24 h (p < 0.05; p < 0.01). The oxidative stress pathway and Toll-like receptor pathway in mouse astrocyte-cerebellum (MA-c) were inhibited (p < 0.05; p < 0.01). Meanwhile, in vitro interaction model results showed that G-Rg2 reduced the activation of MA-c, thereby alleviating the degradation of TJs in bEnd3 (p < 0.05; p < 0.01). The co-culture system of MA-c and bEnd3 further clearly demonstrated that G-Rg2 (20 µM) could improve their interaction and enhance BBB tightness. CONCLUSION: This study suggests that G-Rg2 can inhibit the TLR4/MyD88/MMP9 inflammatory pathway by reducing the activation of MA-c and the binding of TLR4 to MyD88, thereby decreasing the secretion of inflammatory factors and matrix metalloproteinases (MMPs), hence maintaining the stability of TJs in bEnd3, which may be one of the mechanisms of G-Rg2 in reducing AD-related BBB damage.

Study of obesity research using machine learning methods: A bibliometric and visualization analysis from 2004 to 2023.

BACKGROUND: Obesity, a multifactorial and complex health condition, has emerged as a significant global public health concern. Integrating machine learning techniques into obesity research offers great promise as an interdisciplinary field, particularly in the screening, diagnosis, and analysis of obesity. Nevertheless, the publications on using machine learning methods in obesity research have not been systematically evaluated. Hence, this study aimed to quantitatively examine, visualize, and analyze the publications concerning the use of machine learning methods in obesity research by means of bibliometrics. METHODS: The Web of Science core collection was the primary database source for this study, which collected publications on obesity research using machine learning methods over the last 20 years from January 1, 2004, to December 31, 2023. Only articles and reviews that fit the criteria were selected for bibliometric analysis, and in terms of language, only English was accepted. VOSviewer, CiteSpace, and Excel were the primary software utilized. RESULTS: Between 2004 and 2023, the number of publications on obesity research using machine learning methods increased exponentially. Eventually, 3286 publications that met the eligibility criteria were searched. According to the collaborative network analysis, the United States has the greatest volume of publications, indicating a significant influence on this research. coauthor's analysis showed the authoritative one in this field is Leo Breiman. Scientific Reports is the most widely published journal. The most referenced publication is "R: a language and environment for statistical computing." An analysis of keywords shows that deep learning, support vector machines, predictive models, gut microbiota, energy expenditure, and genome are hot topics in this field. Future research directions may include the relationship between obesity and its consequences, such as diabetic retinopathy, as well as the interaction between obesity and epidemiology, such as COVID-19. CONCLUSION: Utilizing bibliometrics as a research tool and methodology, this study, for the first time, reveals the intrinsic relationship and developmental pattern among obesity research using machine learning methods, which provides academic references for clinicians and researchers in understanding the hotspots and cutting-edge issues as well as the developmental trend in this field to detect patients' obesity problems early and develop personalized treatment plans.

Exosomal AC068768.1 enhances the proliferation, migration, and invasion of laryngeal squamous cell carcinoma through miR-139-5p/NOTCH1 axis.

Objective: Long non-coding RNAs (lncRNAs) are closely associated with the pathogenesis of laryngeal squamous cell carcinoma (LSCC). This study aimed to investigate the roles of AC068768.1 in LSCC. Methods: Exosomes were extracted by ultracentrifugation and identified by transmission electron microscopy (TEM) assay. The expression levels of mRNA and miRNA were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cellular functions were assesses through immunofluorescence, flow cytometry, colony formation, wound healing and transwell assays. Chromatin immunoprecipitation (ChIP) and luciferase assays were conducted to verify the binding of AC068768.1 by signal transducer and activator of transcription 3 (STAT3). Xenograft assays were performed to confirm the roles of AC068768.1 in LSCC, and hematoxylin-eosin (HE) staining was applied for histological analysis. Results: LSCC cell-derived exosomes induced M2-like tumor-associated macrophages (TAM2) polarization, which promoted the proliferation, migration, and invasion of LSCCs. Knockdown of exosomal AC068768.1 inhibited M2 polarization and suppressed LSCC aggressiveness both in vitro and in vivo. Moreover, AC068768.1 sponged miR-139-5p, inducing the upregulation of neurogenic locus notch homolog protein 1 (NOTCH1). LSCCs adapted to TAM2 polarization in the tumor microenvironment via AC068768.1-mediated activation of the NOTCH1 pathway. Additionally, NOTCH1 activated STAT3. Conclusion: The AC068768.1/miR-139-5p/NOTCH1/STAT3 axis promotes the metastasis of LSCC. This finding may provide a novel target for LSCC therapy.

Aggregation-Induced Enhanced Red Emission Graphene Quantum Dots for Integrated Fabrication of Luminescent Solar Concentrators.

Graphene quantum dots (GQDs) commonly suffer from the fluorescence problem of aggregation-caused quenching under high-concentration loading or in the solid state, which seriously hinders the application. Here we report a type of GQDs with red aggregation-induced enhanced emission (AIEE). It is confirmed that the aggregation state of the AIEE GQDs is a J-aggregate. The GQDs/poly(methyl methacrylate) film presented a photoluminescence quantum yield as high as 60.81%, and the record-high performance of luminescent solar concentrators (LSCs) was achieved. The power conversion efficiency (ηPCE) is up to 8.35% and the external optical efficiency (ηext) is ∼8.99% for the GQD-based LSCs (45 mW/cm2). Even under one sun illumination (100 mW/cm2), the corresponding ηPCE and ηext values are 3.12% and 4.52%, respectively. The internal photon efficiency (ηint) of an LSC device is about 5.02%. The synthesis of AIEE GQDs bridges the research gap in the emission mechanism of AIEE in GQDs.

Hydrogel Microneedle Patches Loaded with Stem Cell Mitochondria-Enriched Microvesicles Boost the Chronic Wound Healing.

Rescuing or compensating mitochondrial function represents a promising therapeutic avenue for radiation-induced chronic wounds. Adult stem cell efficacies are primarily dependent on the paracrine secretion of mitochondria-containing extracellular vesicles (EVs). However, effective therapeutic strategies addressing the quantity of mitochondria and mitochondria-delivery system are lacking. Thus, in this study, we aimed to design an effective hydrogel microneedle patch (MNP) loaded with stem cell-derived mitochondria-rich EVs to gradually release and deliver mitochondria into the wound tissues and boost wound healing. We, first, used metformin to enhance mitochondrial biogenesis and thereby increasing the secretion of mitochondria-containing EVs (termed "Met-EVs") in adipose-derived stem cells. To verify the therapeutic effects of Met-EVs, we established an in vitro and an in vivo model of X-ray-induced mitochondrial dysfunction. The Met-EVs ameliorated the mitochondrial dysfunction by rescuing mitochondrial membrane potential, increasing adenosine 5'-triphosphate levels, and decreasing reactive oxygen species production by transferring active mitochondria. To sustain the release of EVs into damaged tissues, we constructed a Met-EVs@Decellularized Adipose Matrix (DAM)/Hyaluronic Acid Methacrylic Acid (HAMA)-MNP. Met-EVs@DAM/HAMA-MNP can load and gradually release Met-EVs and their contained mitochondria into wound tissues to alleviate mitochondrial dysfunction. Moreover, we found Met-EVs@DAM/HAMA-MNP can markedly promote macrophage polarization toward the M2 subtype with anti-inflammatory and regenerative functions, which can, in turn, enhance the healing process in mice with skin wounds combined radiation injuries. Collectively, we successfully fabricated a delivery system for EVs, Met-EVs@DAM/HAMA-MNP, to effectively deliver stem cell-derived mitochondria-rich EVs. The effectiveness of this system has been demonstrated, holding great potential for chronic wound treatments in clinic.

Schisandra chinensis inhibits the entry of BoHV-1 by blocking PI3K-Akt pathway and enhances the m6A methylation of gD to inhibit the entry of progeny virus.

Schisandra chinensis, a traditional Chinese medicine known for its antitussive and sedative effects, has shown promise in preventing various viral infections. Bovine herpesvirus-1 (BoHV-1) is an enveloped DNA virus that causes respiratory disease in cattle, leading to significant economic losses in the industry. Because the lack of previous reports on Schisandra chinensis resisting BoHV-1 infection, this study aimed to investigate the specific mechanisms involved. Results from TCID50, qPCR, IFA, and western blot analyses demonstrated that Schisandra chinensis could inhibit BoHV-1 entry into MDBK cells, primarily through its extract Methylgomisin O (Meth O). The specific mechanism involved Meth O blocking BoHV-1 entry into cells via clathrin- and caveolin-mediated endocytosis by suppressing the activation of PI3K-Akt signaling pathway. Additionally, findings from TCID50, qPCR, co-immunoprecipitation and western blot assays revealed that Schisandra chinensis blocked BoHV-1 gD transcription through enhancing m6A methylation of gD after virus entry, thereby hindering gD protein expression and preventing progeny virus entry into cells and ultimately inhibiting BoHV-1 replication. Overall, these results suggest that Schisandra chinensis can resist BoHV-1 infection by targeting the PI3K-Akt signaling pathway and inhibiting gD transcription.

Modeling of a Single-Band-Ratiometric Sensor Based on Lattice Positive Thermal Expansion in Eu3+-Activated Halide Perovskite Cs2NaEuCl6.

Recently, single-band ratiometric (SBR) thermometry has emerged as an innovative approach to traditional fluorescence thermometry, overcoming uncertainties associated with emission spectrum overlap or scattering while maintaining high spatial resolution and remote monitoring. This paper presents a novel Cs2NaEuCl6 perovskite prepared through a slow-cooling solution method. Additionally, it proposes a temperature sensor model that relies on the thermal quenching of charge-transfer state absorption. Mechanical studies highlight the role of lattice positive thermal expansion in affecting Eu3+ emission. Conversely, a significant emission enhancement is observed upon excitation corresponding to both the ground state and excited state absorption. The distinct luminescent behavior of this Eu3+-activated halide perovskite model makes it suitable for developing a highly sensitive SBR-type sensor with a relative sensitivity (Sr) exceeding 1.5% K-1 and temperature resolution (𝛿T) below 1 K at room temperature. Furthermore, it demonstrates the thermal stability during multiple heating-cooling cycles. Finally, the practical applicability of the proposed SBR model is demonstrated by employing a self-manufactured film sensor that enables precise real-time temperature detection for electronic components. The work is regarded as a significant stride toward the development of cutting-edge and exquisitely sensitive thermometers based on lanthanide-based halide double perovskites.

Ginsenoside Rg2 Attenuates Aging-Induced Liver Injury via Inhibiting Caspase 8-Mediated Pyroptosis, Apoptosis and Modulating Gut Microbiota.

Aging is an irresistible natural law of the progressive decline of body molecules, organs, and overall function with the passage of time, resulting in eventual death. World Health Organization data show that aging is correlated with a wide range of common chronic diseases in the elderly, and is an essential driver of many diseases. Panax Ginseng C.A Meyer is an ancient herbal medicine, which has an effect of "long service, light weight, and longevity" recorded in the ancient Chinese medicine book "Compendium of Materia Medica." Ginsenoside Rg2, the main active ingredient of ginseng, also exerts a marked effect on the treatment of liver injury. However, it remains unclear whether Rg2 has the potential to ameliorate aging-induced liver injury. Hence, exploring the hepatoprotective properties of Rg2 and its possible molecular mechanism by Senescence Accelerate Mouse Prone 8 (SAMP8) and gut microbiota. Our study demonstrated that Rg2 can inhibit pyroptosis and apoptosis through caspase 8, and regulate the gut-liver axis to alleviate liver inflammation by changing the composition of gut microbiota, thus improving aging-induced liver injury. These findings provide theoretical support for the pharmacological effects of ginsenosides in delaying aging-induced liver injury.

Thin film ferroelectric photonic-electronic memory.

To reduce system complexity and bridge the interface between electronic and photonic circuits, there is a high demand for a non-volatile memory that can be accessed both electrically and optically. However, practical solutions are still lacking when considering the potential for large-scale complementary metal-oxide semiconductor compatible integration. Here, we present an experimental demonstration of a non-volatile photonic-electronic memory based on a 3-dimensional monolithic integrated ferroelectric-silicon ring resonator. We successfully demonstrate programming and erasing the memory using both electrical and optical methods, assisted by optical-to-electrical-to-optical conversion. The memory cell exhibits a high optical extinction ratio of 6.6 dB at a low working voltage of 5 V and an endurance of 4 × 104 cycles. Furthermore, the multi-level storage capability is analyzed in detail, revealing stable performance with a raw bit-error-rate smaller than 5.9 × 10-2. This ground-breaking work could be a key technology enabler for future hybrid electronic-photonic systems, targeting a wide range of applications such as photonic interconnect, high-speed data communication, and neuromorphic computing.

Hydrogen Sulfide Improves Postharvest Quality of Okra (Abelmoschus esculentus (L.) Moench) Pods by Enhancing Antioxidant Capacity and Delaying Lignification.

Okra (Abelmoschus esculentus (L.) Moench) pod storage is challenging due to its high water content and tendency to lignify. Sodium hydrosulfide (NaHS) served as an H2S donor in this investigation. Compared with the control group, the group treated with 0.5 mmol/L NaHS solution effectively maintained the appearance quality, and its weight loss was only 6.21% at 20 days. The H2S treatment not only preserved tissue nutrients but also significantly enhanced catalase (CAT), ascorbic acid peroxidase (APX), and superoxide dismutase (SOD) activities while decreasing oxidant damage. In addition, H2S slowed down lignin synthesis by inhibiting the activities of key enzymes such as phenylalanine ammonialyase (PAL), cinnamate 4-hydroxylase (C4H), and cinnamyl alcohol dehydrogenase (CAD) in the lignin biosynthesis pathway. Transcriptome analysis revealed that H2S affects 34 genes in the phenylpropanoid biosynthesis pathway, such as AePAL, Ae4CL1, AeCCOAOMT1, AePOD, etc., which inhibit lignin synthesis of okra pods. All in all, moderate H2S can improve postharvest quality and extend the shelf-life of okra pods by enhancing antioxidant capacity and delaying lignification; the results will provide an overview of its application in the preservation of okra pods.

[Role and mechanism of epithelial-mesenchymal transition in a rat model of bronchopulmonary dysplasia induced by hyperoxia exposure]. / 上皮-间å è´¨è½¬åŒ–åœ¨é«˜æ°§è¯±å¯¼å¤§é¼ æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯æ¨¡åž‹ä¸­çš„ä½œç”¨åŠæœºåˆ¶ç ”ç©¶.

OBJECTIVES: To investigate the role and mechanism of epithelial-mesenchymal transition (EMT) in a rat model of bronchopulmonary dysplasia (BPD). METHODS: The experiment consisted of two parts. (1) Forty-eight preterm rats were randomly divided into a normoxia group and a hyperoxia group, with 24 rats in each group. The hyperoxia group was exposed to 85% oxygen to establish a BPD model, while the normoxia group was kept in room air at normal pressure. Lung tissue samples were collected on days 1, 4, 7, and 14 of the experiment. (2) Rat type II alveolar epithelial cells (RLE-6TN) were randomly divided into a normoxia group (cultured in air) and a hyperoxia group (cultured in 95% oxygen), and cell samples were collected 12, 24, and 48 hours after hyperoxia exposure. Hematoxylin-eosin staining was used to observe alveolarization in preterm rat lungs, and immunofluorescence was used to detect the co-localization of surfactant protein C (SPC) and α-smooth muscle actin (α-SMA) in preterm rat lung tissue and RLE-6TN cells. Quantitative real-time polymerase chain reaction and protein immunoblotting were used to detect the expression levels of EMT-related mRNA and proteins in preterm rat lung tissue and RLE-6TN cells. RESULTS: (1) Compared with the normoxia group, the hyperoxia group showed blocked alveolarization and simplified alveolar structure after 7 days of hyperoxia exposure. Co-localization of SPC and α-SMA was observed in lung tissue, with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 7 and 14 days of hyperoxia exposure compared to the normoxia group. In the hyperoxia group, the mRNA and protein levels of TGF-ß1, α-SMA, and N-cadherin were increased, while the mRNA and protein levels of SPC and E-cadherin were decreased at 7 and 14 days of hyperoxia exposure compared to the normoxia group (P<0.05). (2) SPC and α-SMA was observed in RLE-6TN cells, with decreased SPC expression and increased α-SMA expression in the hyperoxia group at 24 and 48 hours of hyperoxia exposure compared to the normoxia group. Compared to the normoxia group, the mRNA and protein levels of SPC and E-cadherin in the hyperoxia group were decreased, while the mRNA and protein levels of TGF-ß1, α-SMA, and E-cadherin in the hyperoxia group increased at 48 hours of hyperoxia exposure (P<0.05). CONCLUSIONS: EMT disrupts the tight connections between alveolar epithelial cells in a preterm rat model of BPD, leading to simplified alveolar structure and abnormal development, and is involved in the development of BPD. Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 765-773.

The response of mesophyll conductance to short-term CO2 variation is related to stomatal conductance.

The response of mesophyll conductance (gm) to CO2 plays a key role in photosynthesis and ecosystem carbon cycles under climate change. Despite numerous studies, there is still debate about how gm responds to short-term CO2 variations. Here we used multiple methods and looked at the relationship between stomatal conductance to CO2 (gsc) and gm to address this aspect. We measured chlorophyll fluorescence parameters and online carbon isotope discrimination (Δ) at different CO2 mole fractions in sunflower (Helianthus annuus L.), cowpea (Vigna unguiculata L.), and wheat (Triticum aestivum L.) leaves. The variable J and Δ based methods showed that gm decreased with an increase in CO2 mole fraction, and so did stomatal conductance. There were linear relationships between gm and gsc across CO2 mole fractions. gm obtained from A-Ci curve fitting method was higher than that from the variable J method and was not representative of gm under the growth CO2 concentration. gm could be estimated by empirical models analogous to the Ball-Berry model and the USO model for stomatal conductance. Our results suggest that gm and gsc respond in a coordinated manner to short-term variations in CO2, providing new insight into the role of gm in photosynthesis modelling.

Clinical efficacy of thalidomide for various genotypes of beta thalassemia.

OBJECTIVE: The objective of this study was to investigate the therapeutic efficacy of thalidomide across various genotype presentations of ß-thalassemia so as to facilitate the early screening of thalidomide-sensitive thalassemia cases and to understand the impact of iron overload on thalidomide. METHODS: From our initial sample of 52 patients, we observed 48 patients with ß-thalassemia for two years after administration of thalidomide. This cohort included 34 patients with transfusion-dependent thalassemia (TDT) and 14 patients with non-transfusion-dependent thalassemia (NTDT). We recorded the values of hemoglobin (Hb), fetal hemoglobin (HbF), and serum ferritin (SF) in the baseline period and at 1, 3, 6, 12, 18, and 24 months after enrollment, as well as the pre- and post-treatment blood transfusion volume in all 48 cases. According to the increase in Hb levels from baseline during the 6-month observation period, the response to thalidomide was divided into four levels: main response (MaR), minor response (MiR), slow response (SLR), and no response (NR). A decrease in serum ferritin levels compared to baseline was considered alleviation of iron overload. We calculated the overall response rate (ORR) as follows: ORR = MaR + MiR + SLR/number of observed cases. RESULTS: The ORR was 91.7% (44/48 cases), and 72.9% showed MaR (35/48 cases). Among the 34 patients with TDT, 21 patients (61.8%) were free of blood transfusion, and the remaining 13 patients still required blood transfusion, but their total blood transfusion volume reduced by 31.3% when compared to the baseline. We found a total of 33 cases with 10 combinations of advantageous genes, which included 5 cases with ßCD41-42/ßCD17 and 6 cases with ßCD41-42/ß-28. Based on the treatment outcomes among the 48 cases in the observation group, there were 33 cases in the MaR group and 15 cases in the SLR/NR group. There was a difference in HbF between the two groups at baseline (P = 0.041). There were significant differences between the two groups in Hb and HbF at the time points of 6 and 12 months, respectively (P < 0.001). Compared to the baseline measurement, there was a significant decrease in the level of SF at months 12 and 24 (P < 0.001). CONCLUSION: In this study, we identified 10 ß-thalassemia gene combinations that were sensitive to thalidomide. These gene combinations can be used for initial screening and to predict the therapeutic effect of thalidomide in clinical practice. We examined the therapeutic response to thalidomide and found that the administration of thalidomide in combination with standardized iron removal was more beneficial in reducing iron overload.

Time-course and dose-effect of omalizumab in treating chronic idiopathic urticaria/chronic spontaneous urticaria.

PURPOSE: Several studies have shown that subcutaneous injections of omalizumab can treat chronic idiopathic/spontaneous urticaria (CIU/CSU) patients by only assessing the efficacy on specific endpoints. This study aimed to quantitatively analyze different doses of omalizumab in CIU/CSU and compare it with ligelizumab. METHODS: Literature searches were performed in PubMed, Embase, and Web of Science databases. A model-based meta-analysis (MBMA) was utilized to develop a model incorporating time since the initiation of treatment and dose for omalizumab, with the change from baseline in Urticaria Activity Score (CFB-UAS7) as the primary efficacy endpoint. The time-course and dose-effect relationship throughout the omalizumab treatment period was analyzed, and the findings were compared with those of the investigational ligelizumab. RESULTS: The model equation for the CFB-UAS7 was established as E = -Emax × time/(ET50 + time) × (b0 + b1 × dose). The estimated values of the model parameters E max , ET 50 , b 0 , and b 1 were -1.16, 1.26 weeks, -9.90, and -0.0361 mg-1, respectively. At week 12 after the first dose, the model-predicted CFB-UAS7 for 150 mg and 300 mg of omalizumab were -16.0 (95% CI, -17.2 to -14.8) and -21.7 (95% CI, -22.9 to -20.5), respectively. In the PEARL-1 trial, the CFB-UAS7 for 72 mg and 120 mg of ligelizumab were -19.4 (95% CI, -20.7 to -18.1) and -19.3 (95% CI, -20.6 to -18.0), respectively. In the PEARL-2 trial, these values were -19.2 (95% CI, -20.5 to -17.9) and -20.3 (95% CI, -21.6 to -19.0), respectively. CONCLUSION: Omalizumab showed a significant dose-dependent effect in the treatment of CSU. Both 72 mg and 120 mg ligelizumab might have the potential to outperform 150 mg (but not 300 mg) omalizumab.

Far-Red Aggregation-Induced Emission Hydrogel-Reinforced Tissue Clearing for 3D Vasculature Imaging of Whole Lung and Whole Tumor.

Understanding the vascular formation and distribution in metastatic lung tumors is a significant challenge due to autofluorescence, antibody/dye diffusion in dense tumor, and fluorophore stability when exposed to solvent-based clearing agents. Here, an approach is presented that redefines 3D vasculature imaging within metastatic tumor, peritumoral lung tissue, and normal lung. Specifically, a far-red aggregation-induced emission nanoparticle with surface amino groups (termed as TSCN nanoparticle, TSCNNP) is designed for in situ formation of hydrogel (TSCNNP@Gel) inside vasculatures to provide structural support and enhance the fluorescence in solvent-based tissue clearing method. Using this TSCNNP@Gel-reinforced tissue clearing imaging approach, the critical challenges are successfully overcome and comprehensive visualization of the whole pulmonary vasculature up to 2 µm resolution is enabled, including its detailed examination in metastatic tumors. Importantly, features of tumor-associated vasculature in 3D panoramic views are unveiled, providing the potential to determine tumor stages, predict tumor progression, and facilitate the histopathological diagnosis of various tumor types.

Functionality of arbuscular mycorrhizal fungi varies across different growth stages of maize under drought conditions.

Physio-biochemical regulations governing crop growth period are pivotal for drought adaptation. Yet, the extent to which functionality of arbuscular mycorrhizal fungi (AM fungi) varies across different stages of maize growth under drought conditions remains uncertain. Therefore, periodic functionality of two different AM fungi i.e., Rhizophagus irregularis SUN16 and Glomus monosporum WUM11 were assessed at jointing, silking, and pre-harvest stages of maize subjected to different soil moisture gradients i.e., well-watered (80% SMC (soil moisture contents)), moderate drought (60% SMC), and severe drought (40% SMC). The study found that AM fungi significantly (p < 0.05) affected various morpho-physiological and biochemical parameters at different growth stages of maize under drought. As the plants matured, AM fungi enhanced root colonization, glomalin contents, and microbial biomass, leading to increased nutrient uptake and antioxidant activity. This boosted AM fungal activity ultimately improved photosynthetic efficiency, evident in increased photosynthetic pigments and photosynthesis. Notably, R. irregularis and G. monosporum improved water use efficiency and mycorrhizal dependency at critical growth stages like silking and pre-harvest, indicating their potential for drought resilience to stabilize yield. The principal component analysis highlighted distinct plant responses to drought across growth stages and AM fungi, emphasizing the importance of early-stage sensitivity. These findings underscore the potential of incorporating AM fungi into agricultural management practices to enhance physiological and biochemical responses, ultimately improving drought tolerance and yield in dryland maize cultivation.

Dual-targeted fluorescent probe for tracking polarity and phase transition processes during lipophagy.

Eukaryotic cells regulate various cellular processes through membrane-bound and membrane-less organelles, enabling active signal communication and material exchange. Lysosomes and lipid droplets are representative organelles, contributing to cell lipophagy when their interaction and metabolism are disrupted. Our limited understanding of the interacting behaviours and physicochemical properties of different organelles during lipophagy hinders accurate diagnosis and treatment of related diseases. In this contribution, we report a fluorescent probe, PTZ, engineered for dual-targeting of lipid droplets and lysosomes. PTZ can track liquid-liquid phase separation and respond to polarity shifts through ratiometric fluorescence emission, elucidating the lipophagy process from the perspective of organelle behavior and physicochemical properties. Leveraging on the multifunctionality of PTZ, we have successfully tracked the polarity and dynamic changes of lysosomes and lipid droplets during lipophagy. Furthermore, an unknown homogeneous transition of lipid droplets and lysosomes was discovered, which provided a new perspective for understanding lipophagy processes. And this work is expected to serve as a reference for diagnosis and treatment of lipophagy-related diseases.

The m6A reader HNRNPC promotes glioma progression by enhancing the stability of IRAK1 mRNA through the MAPK pathway.

Glioma is the most common and aggressive type of primary malignant brain tumor. The N6-methyladenosine (m6A) modification widely exists in eukaryotic cells and plays an important role in the occurrence and development of human tumors. However, the function and mechanism of heterogeneous nuclear ribonucleoprotein C (HNRNPC), an RNA-binding protein and m6A reader in gliomas remains to be comprehensively and extensively explored. Herein, we found that HNRNPC mRNA and protein overexpression were associated with a poor prognosis for patients with gliomas, based on the data from TCGA, the CGGA, and the TMAs. Biologically, HNRNPC knockdown markedly repressed malignant phenotypes of glioma in vitro and in vivo, whereas ectopic HNRNPC expression had the opposite effect. Integrative RNA sequencing and MeRIP sequencing analyses identified interleukin-1 receptor-associated kinase 1 (IRAK1) as a downstream target of HNRNPC. The glioma public datasets and tissue microarrays (TMAs) data indicated that IRAK1 overexpression was associated with poor prognosis, and IRAK1 knockdown significantly repressed malignant biological behavior in vitro. Mechanistically, HNRNPC maintains the mRNA stability of IRAK1 in an m6A-dependent manner, resulting in activation of the mitogen-activated protein kinase (MAPK) signaling pathway, which was necessary for the malignant behavior of glioma. Our findings demonstrate the HNRNPC-IRAK1-MAPK axis as a crucial carcinogenic factor for glioma and the novel underlying mechanism of IRAK1 upregulation, which provides a rationale for therapeutically targeting epitranscriptomic modulators in glioma.

Stable and Durable Superhydrophobic Cotton Fabrics Prepared via a Simple 1,4-Conjugate Addition Reaction for Ultrahigh Efficient Oil-Water Separation.

Superhydrophobic materials used for oil-water separation have received wide attention. However, the simple and low-cost strategy for making durable superhydrophobic materials remains a major challenge. Here, this work reports that stable and durable superhydrophobic cotton fabrics can be prepared using a simple two-step impregnation process. Silica nanoparticles are surface modified by hydrolysis condensation of 3-aminopropyltrimethoxysilane (APTMS). 1,4-conjugate addition reaction between the acrylic group of cross-linking agent pentaerythritol triacrylate (PETA) and the amino group of octadecylamine (ODA) forms a covalent cross-linked rough network structure. The long hydrophobic chain of ODA makes the cotton fabric exhibit excellent superhydrophobic properties, and the water contact angle (WCA) of the fabric surface reaches 158°. The modified cotton fabric has good physical and chemical stability, self-cleaning, and anti-fouling. At the same time, the modified fabric shows excellent oil/water separation efficiency (98.16% after 20 cycles) and ultrahigh separation flux (15413.63 L m-2 h-1) due to its superhydrophobicity, superoleophilicity, and inherent porous structure. The method provides a broad prospect in the future diversification applications of oil/water separation and oil spill cleaning.