Protective Effects of Bioactive Compound-Derived Nanoparticle Against Diabetic Retinopathy Through the Modulation of the NF-κB Signaling Pathway.

Diabetic retinopathy is a prevalent and severe microvascular complication of diabetes, often causing visual impairment and blindness in adults. This condition significantly impacts the quality of life for many diabetes patients worldwide. Berberine (BBR), a bioactive compound known for its effects on blood glucose levels, has shown promise in managing diabetic complications. However, the exact mechanism of how BBR influences the development of diabetic retinopathy remains unclear. In this study, we focused on synthesizing a formulation derived from BBR and assessing its protective effects against diabetic retinopathy. The formulation was created using a green synthesis method and thoroughly characterized. In vitro studies demonstrated the antioxidant activity of the formulation against 2,2-diphenyl-1-picryl-hydrazyl-hydrate. We also examined the NF-κB signaling pathway at a molecular level using real-time polymerase chain reaction. To mimic diabetic retinopathy in a controlled setting, a diabetic rat model was established through streptozotocin injection. The rats were divided into normal, diabetic, and treatment groups. The treatment group received the formulated treatment via intragastric administration for several weeks, while the other groups received normal saline. Evaluation of histopathological characteristics and microstructural changes in the retina using hematoxylin and eosin staining revealed that the bioactive compound-derived nanoparticle exhibited favorable biological, chemical, and physical properties. Treatment with the formulation effectively reduced oxidative stress induced by diabetes and inhibited the NF-κB signaling pathway in the diabetic rat model. Under high glucose conditions, oxidative stress was heightened, leading to mitochondria-dependent cell apoptosis in Müller cells via the activation of the NF-κB signaling pathway. The bioactive compound-derived formulation counteracted these effects by decreasing IκB phosphorylation, preventing NF-κB nuclear translocation, and deactivating the NF-κB signaling pathway. Furthermore, treatment with the bioactive compound-derived formulation mitigated retinal micro- and ultrastructural changes associated with diabetic retinopathy. These results indicate that the formulation protects against diabetic retinopathy by suppressing oxidative stress, reducing cell apoptosis, and deactivating the NF-κB signaling pathway. This suggests that the bioactive compound-derived formulation could be a promising therapeutic option for diabetic retinopathy.

Exploring research hotspots and future directions in neural tube defects field by bibliometric and bioinformatics analysis.

Background: Neural tube defects (NTDs) is the most common birth defect of the central nervous system (CNS) which causes the death of almost 88,000 people every year around the world. Much efforts have been made to investigate the reasons that contribute to NTD and explore new ways to for prevention. We trawl the past decade (2013-2022) published records in order to get a worldwide view about NTDs research field. Methods: 7,437 records about NTDs were retrieved from the Web of Science (WOS) database. Tools such as shell scripts, VOSviewer, SCImago Graphica, CiteSpace and PubTator were used for data analysis and visualization. Results: Over the past decade, the number of publications has maintained an upward trend, except for 2022. The United States is the country with the highest number of publications and also with the closest collaboration with other countries. Baylor College of Medicine has the closest collaboration with other institutions worldwide and also was the most prolific institution. In the field of NTDs, research focuses on molecular mechanisms such as genes and signaling pathways related to folate metabolism, neurogenic diseases caused by neural tube closure disorders such as myelomeningocele and spina bifida, and prevention and treatment such as folate supplementation and surgical procedures. Most NTDs related genes are related to development, cell projection parts, and molecular binding. These genes are mainly concentrated in cancer, Wnt, MAPK, PI3K-Akt and other signaling pathways. The distribution of NTDs related SNPs on chromosomes 1, 3, 5, 11, 14, and 17 are relatively concentrated, which may be associated with high-risk of NTDs. Conclusion: Bibliometric analysis of the literature on NTDs field provided the current status, hotspots and future directions to some extant. Further bioinformatics analysis expanded our understanding of NTDs-related genes function and revealed some important SNP clusters and loci. This study provided some guidance for further studies. More extensive cooperation and further research are needed to overcome the ongoing challenge in pathogenesis, prevention and treatment of NTDs.

The quantitative parameters based on marrow metabolism derived from synthetic MRI: A pilot study of prognostic value in participants with newly diagnosed multiple myeloma.

BACKGROUND: The value of SyMRI-derived parameters from lumbar marrow for predicting early treatment response and optimizing the risk stratification of the Revised International Staging System (R-ISS) in participants with multiple myeloma (MM) is unknown. METHODS: We prospectively enrolled participants with newly diagnosed MM before treatment. The SyMRI of lumbar marrow was used to calculate T1, T2, and PD values and the clinical features were collected. All participants were divided into good response (≥VGPR) and poor response (

Simultaneous production of algal biomass and lipid by heterotrophic cultivation of linoleic acid-rich oleaginous microalga Chlorella sorokiniana using high acetate dosage.

The low-cost carbon source, acetate, was utilized to feed a linoleic acid-rich Chlorella sorokiniana for microalgal biomass and lipid accumulation. Remarkably high tolerance capability to high acetate dosage up to 30 g/L was observed, with heterotrophy being the preferred trophic mode for algal growth and lipogenesis when supplemented 20 g/L acetate. Transcriptome analysis revealed a marked activation of pathways involved in acetate bioconversion and lipogenesis upon exposure to high-level of acetate. However, the enhancement of photorespiration inhibited photosynthesis, which ultimately led to a decrease in biomass and lipid under mixotrophy. Heterotrophic acetate-feeding generated more superior amino acid profiling of algal biomass and a predominant linoleic acid content (50 %). Heterotrophic repeat fed-batch strategy in 5 L fermenter significantly increased the growth performance and lipid titer, with the highest levels achieved being 23.4 g/L and 7.0 g/L, respectively. This work provides a viable approach for bio-products production through acetate-based heterotrophic algal cultivation.

Development of a whole spinal MRI-based tumor burden scoring method in participants with multiple myeloma: a pilot study of prognostic significance.

The aim of the study was to develop a new whole spinal MRI-based tumor burden scoring method in participants with newly diagnosed multiple myeloma (MM) and to explore its prognostic significance. We prospectively recruited participants with newly diagnosed MM; performed whole spinal MRI (sagittal FSE T1WI, sagittal IDEAL T2WI, and axial FLAIR T2WI) on them; and collected their clinical data, early treatment response, progression-free survival (PFS), and overall survival (OS). We developed a new tumor burden scoring method according to the extent of bone marrow infiltration in five MRI patterns. All participants were divided into good response and poor response groups after four treatment cycles. Univariate, multivariate analyses, and ROC were used to determine the performance of independent predictors. Thresholds for PFS and OS were calculated using X-tile, and their prognostic significance were assessed by Kaplan-Meier. The Kruskal-Wallis H test was used to compare the differences of tumor burden score between the revised International Staging System (R-ISS) stages. The new tumor burden scoring method was used in 62 participants (median score, 12; range, 0-18). The tumor burden score (OR 1.266, p = 0.002) was an independent predictor of poor response and the AUC was 0.838. Higher tumor burden scores were associated with shorter PFS (p = 0.002) and OS (p = 0.011). The tumor burden score was higher in R-ISS-III than in R-ISS-I and R-ISS-II (p = 0.016 and p = 0.006, respectively). The tumor burden score was an excellent predictor of prognosis and may serve as a supplemental marker for R-ISS.

Economic co-production of cellulosic ethanol and microalgal biomass through efficient fixation of fermentation carbon dioxide.

An integrated process for the co-production of cellulosic ethanol and microalgal biomass by fixing CO2 generated from bioethanol fermentation is proposed. Specifically, over one-fifth of the fermentative carbon was converted into high-purity CO2 during ethanol production. The optimal concentration of 4 % CO2 was identified for the growth and metabolism of Chlorella sp. BWY-1. A multiple short-term intermittent CO2 supply system was established to efficiently fix and recycle the waste CO2. Using this system, economical co-production of cellulosic ethanol by Zymomonas mobilis and microalgal biomass in biogas slurry wastewater was achieved, resulting in the production of ethanol at a rate of 0.4 g/L/h and a fixed fermentation CO2 of 3.1 g/L/d. Moreover, the amounts of algal biomass and chlorophyll a increased by over 50 % and two-fold, respectively. Through techno-economic analysis, the integrated process demonstrated its cost-effectiveness for cellulosic ethanol production. This study presents an innovative approach to a low-carbon circular bioeconomy.

Predicting the status of lymphovascular space invasion using quantitative parameters from synthetic MRI in cervical squamous cell carcinoma without lymphatic metastasis.

Purpose: To investigate the value of quantitative longitudinal relaxation time (T1), transverse relaxation time (T2), and proton density (PD) maps derived from synthetic magnetic resonance imaging (MRI) for evaluating the status of lymphovascular space invasion (LVSI) in cervical squamous cell carcinoma (CSCC) without lymph node metastasis (LNM). Material and methods: Patients with suspected cervical cancer who visited our hospital from May 2020 to March 2023 were collected. All patients underwent preoperative MRI, including routine sequences and synthetic MRI. Patients with pathologically confirmed CSCC without lymphatic metastasis were included in this study. The subjects were divided into negative- and positive-LVSI groups based on the status of LVSI. Quantitative parameters of T1, T2, and PD values derived from synthetic MRI were compared between the two groups using independent samples t-test. Receiver operating characteristic curves were used to determine the diagnostic efficacy of the parameters. Results: 59 patients were enrolled in this study and were classified as positive (n = 32) and negative LVSI groups (n = 27). T1 and T2 values showed significant differences in differentiating negative-LVSI from positive-LVSI CSCC (1307.39 ± 122.02 vs. 1193.03 ± 107.86, P<0.0001; 88.42 ± 7.24 vs. 80.99 ± 5.50, P<0.0001, respectively). The area under the curve (AUC) for T1, T2 values and a combination of T1 and T2 values were 0.756, 0.799, 0.834 respectively, and there is no statistically significant difference in the diagnostic efficacy between individual and combined diagnosis of each parameter. Conclusions: Quantitative parameters derived from synthetic MRI can be used to evaluate the LVSI status in patients with CSCC without LNM.

Tailoring the composition, antioxidant activity, and prebiotic potential of apple peel by Aspergillus oryzae fermentation.

Apple peel is a typical lignocellulosic food by-product rich in functional components. In this work, apple peel was solid-state fermented with Aspergillus oryzae with an aim to modulate its composition and bioactivity. The results showed that A. oryzae fermentation substantially tailored the composition, improved the antioxidant activity and prebiotic potential of apple peel. Upon the fermentation, 1) free phenolics increased and antioxidant activity improved; 2) the pectin substances degraded significantly, along with a decrease in soluble dietary fiber while an increase in insoluble dietary fiber; 3) the in vitro fermentability increased as indicated by the increase in total acid production. The gut microbiota was shaped with more health-promoting potentials, such as higher abundances of Lactobacillus, Bifidobacterium, Megamonas and Prevotella-9 as well as lower abundances of Enterobacter and Echerichia-Shigella. This work is conducive to the modification of apple peel as a potential ingredient in food formulations.

Coherently parallel fiber-optic distributed acoustic sensing using dual Kerr soliton microcombs.

Fiber-optic distributed acoustic sensing (DAS) has proven to be a revolutionary technology for the detection of seismic and acoustic waves with ultralarge scale and ultrahigh sensitivity, and is widely used in oil/gas industry and intrusion monitoring. Nowadays, the single-frequency laser source in DAS becomes one of the bottlenecks limiting its advance. Here, we report a dual-comb-based coherently parallel DAS concept, enabling linear superposition of sensing signals scaling with the comb-line number to result in unprecedented sensitivity enhancement, straightforward fading suppression, and high-power Brillouin-free transmission that can extend the detection distance considerably. Leveraging 10-line comb pairs, a world-class detection limit of 560 fε/√Hz@1 kHz with 5 m spatial resolution is achieved. Such a combination of dual-comb metrology and DAS technology may open an era of extremely sensitive DAS at the fε/√Hz level, leading to the creation of next-generation distributed geophones and sonars.

Intravoxel incoherent motion diffusion-weighted MRI for the evaluation of early spleen involvement in acute leukemia.

Background: The spleen is a frequent organ of leukemia metastasis. This study aimed to investigate the value of intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) for assessing pathologic changes in the spleen and identifying early spleen involvement in patients with acute leukemia (AL). Methods: Patients with newly diagnosed AL and healthy controls were recruited between June 2020 and November 2022. All participants underwent abdominal IVIM diffusion-weighted imaging (DWI) at our hospital. IVIM parameters [pure diffusion coefficient (D); pseudo-diffusion coefficient (D*); and pseudo-perfusion fraction (f)] of the spleen were calculated by the segmented fitting method, and perfusion-diffusion ratio (PDR) was further calculated from the values of D, D* and f. Spleen volumes (SVs) were obtained by manually segmenting the spleen layer by layer. Clinical biomarkers of AL patients were collected. Patients were divided into splenomegaly group and normal SV group according to the individualized reference intervals for SV. IVIM parameters were compared among the control group, AL with normal SV group, and AL with splenomegaly group using one-way analysis of variance, followed by pairwise post hoc comparisons. The correlations of IVIM parameters with clinical biomarkers were analyzed in AL patients. The diagnostic performances of IVIM parameters and their combinations for differentiating among the three groups were compared. Results: Seventy-nine AL patients (AL with splenomegaly: n=54; AL with normal SV: n=25) and 55 healthy controls were evaluated. IVIM parameters were significantly different among the three groups (P<0.001 for D, D* and f; P=0.001 for PDR). D and PDR showed significant differences between the control and AL with normal SV groups in pairwise comparisons (P<0.001, and P=0.031, respectively). D was correlated with white blood cell (WBC) counts (r=-0.424; 95% CI: -0.570, -0.211; P<0.001), lactate dehydrogenase (LDH) (r=-0.285; 95% CI: -0.486, -0.011; P=0.011), and bone marrow blasts (r=-0.283; 95% CI: -0.476, -0.067; P=0.012). D* (r=-0.276; 95% CI: -0.470, -0.025; P=0.014), f (r=0.514; 95% CI: 0.342, 0.664; P<0.001) and PDR (r=0.343; 95% CI: 0.208, 0.549; P=0.002) were correlated with LDH. The combination of IVIM parameters (AUC: 0.830; 95% CI: 0.729, 0.905) demonstrated better diagnostic efficacy than the single D* (AUC: 0.721; 95% CI: 0.608, 0.816; Delong test: Z=2.012, P=0.044) and f (AUC: 0.647; 95% CI: 0.532, 0.752; Delong test: Z=2.829, P=0.005), but was not significantly different from the single D (AUC: 0.756; 95% CI: 0.647, 0.846; Delong test: Z=1.676, P=0.094) in differentiating the splenomegaly group and normal SV group. Conclusions: IVIM diffusion-weighted MRI could be a potential alternative for assessing pathologic changes in the spleen from cellularity and angiogenesis, and D and PDR may be viable indicators to identify early spleen involvement in patients with AL.

Melatonin alleviates valproic acid-induced neural tube defects by modulating Src/PI3K/ERK signaling and oxidative stress.

Neural tube defects (NTDs) represent a developmental disorder of the nervous system that can lead to significant disability in children and impose substantial social burdens. Valproic acid (VPA), a widely prescribed first-line antiepileptic drug for epilepsy and various neurological conditions, has been associated with a 4-fold increase in the risk of NTDs when used during pregnancy. Consequently, urgent efforts are required to identify innovative prevention and treatment approaches for VPA-induced NTDs. Studies have demonstrated that the disruption in the delicate balance between cell proliferation and apoptosis is a crucial factor contributing to NTDs induced by VPA. Encouragingly, our current data reveal that melatonin (MT) significantly inhibits apoptosis while promoting the restoration of neuroepithelial cell proliferation impaired by VPA. Moreover, further investigations demonstrate that MT substantially reduces the incidence of neural tube malformations resulted from VPA exposure, primarily by suppressing apoptosis through the modulation of intracellular reactive oxygen species levels. In addition, the Src/PI3K/ERK signaling pathway appears to play a pivotal role in VPA-induced NTDs, with significant inhibition observed in the affected samples. Notably, MT treatment successfully reinstates Src/PI3K/ERK signaling, thereby offering a potential underlying mechanism for the protective effects of MT against VPA-induced NTDs. In summary, our current study substantiates the considerable protective potential of MT in mitigating VPA-triggered NTDs, thereby offering valuable strategies for the clinical management of VPA-related birth defects.

Metformin Preserves Insulin Secretion in Pancreatic ß-cells through FGF21/Akt Pathway In vitro and In vivo.

BACKGROUND: In our previous studies, it was found that metformin can elevate the expression of FGF21 in the peripheral blood of type 2 diabetic rats and improve insulin sensitivity in diabetic rats. However, whether this effect is mediated by increased FGF21 expression in pancreatic islet ß-cells is still unknown. Therefore, this study focuses on the effect of metformin on insulin secretion in pancreatic ß-cells. AIMS: Metformin can effectivly improve insulin resistance. Metformin influencing pancreatic ßcell function is inclusive. In this study, we sought to analyze possible variations in insulin secretion and possible signaling mechanisms after metformin intervention. METHODS: The study employed an in vivo model of a high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic ß-cells (INS-1 cells) that were subjected to damage caused by hyperglycemia and hyperlipidemia. After treating INS-1 cells in normal, high-glucose, and high-glucose+metformin, we measured insulin secretion by glucose-stimulated insulin secretion (GSIS). Insulin was measured using an enzyme-linked immunosorbent assay. FGF21 expression was detected by RT-PCR and Western blot, as well as that p-Akt and t-Akt expression were detected by Western blot in INS-1 cells and diabetic rat islets. Finally, to verify the regulation of the FGF21 /Akt axis in metformin administration, additional experiments were carried out in metformin-stimulated INS-1 cells. RESULTS: High-glucose could significantly stimulate insulin secretion while metformin preserved insulin secretion. Expression of FGF21 and p-Akt was decreased in high-glucose, however, metformin could reverse this effect in INS-1 cells and diabetic rat islets. CONCLUSION: Our results demonstrate a protective role of metformin in preserving insulin secretion through FGF21/Akt signaling in T2DM.

Quantitative tumor burden imaging parameters of the spleen at MRI for predicting treatment response in patients with acute leukemia.

Objectives: To study the value of standardized volume and intravoxel incoherent motion (IVIM) parameters of the spleen based on tumor burden for predicting treatment response in newly diagnosed acute leukemia (AL). Methods: Patients with newly diagnosed AL were recruited and underwent abdominal IVIM diffusion-weighted imaging within one week before the first induction chemotherapy. Quantitative parameters of magnetic resonance imaging (MRI) included the standardized volume (representing volumetric tumor burden) and IVIM parameters (standard apparent diffusion coefficient [sADC]; pure diffusion coefficient [D]; pseudo-diffusion coefficient [D∗]; and pseudo-perfusion fraction [f], representing functional tumor burden) of the spleen. Clinical biomarkers of tumor burden were collected. Patients were divided into complete remission (CR) and non-CR groups according to the treatment response after the first standardized induction chemotherapy, and the MRI and clinical parameters were compared between the two groups. The correlations of MRI parameters with clinical biomarkers were analyzed. Multivariate logistic regression was performed to determine the independent predictors for treatment response. Receiver operating characteristic curves were used to analyze the predicted performance. Results: 76 AL patients (CR: n = 43; non-CR: n = 33) were evaluated. Standardized spleen volume, sADC, D, f, white blood cell counts, and lactate dehydrogenase were significantly different between CR and non-CR groups (all p < 0.05). Standardized spleen volume, sADC, and D were correlated with white blood cell and lactate dehydrogenase, and f was correlated with lactate dehydrogenase (all p < 0.05). Standardized spleen volume (hazard ratio = 4.055, p = 0.042), D (hazard ratio = 0.991, p = 0.027), and f (hazard ratio = 1.142, p = 0.008) were independent predictors for treatment response, and the combination of standardized spleen volume, D, and f showed more favorable discrimination (area under the curve = 0.856) than individual predictors. Conclusion: Standardized volume, D, and f of the spleen could be used to predict treatment response in newly diagnosed AL, and the combination of morphological and functional parameters would further improve the predicted performance. IVIM parameters of the spleen may be viable indicators for evaluating functional tumor burden in AL.

Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice.

Poor tendon-bone interface (TBI) integration is one of the major causes contributing to unsatisfactory healing quality in patients after anterior cruciate ligament (ACL) reconstruction. Type H vessels have been recently found to closely modulate bone formation via regulation of the osteo-angiogenic crosstalk, so the strategies favoring type H vessel formation may be promising therapeutic approaches for improved graft osteointegration. In this study, we reported for the first time the treatment outcome of slit guidance ligand 3 (slit3), a novel proangiogenic factor favoring type H vessel formation, in TBI healing in mice with ACL reconstruction. The mice (n = 87) were divided into three groups for various treatments: hydrogel microparticles (HMP, control group), slit3@HMP, and slit3 neutralizing antibody@HMP (slit3-AB@HMP). Histological analysis, gait performance, radiographic measurement, and biomechanical testing were performed to assess the TBI healing quality. Increased bony ingrowth and reduced fibrous scar tissue was formed at the TBI in the slit3@HMP group when compared to the HMP group. Meanwhile, the slit3-AB@HMP inhibited the osseous ingrowth and increased fibrous scar tissue formation relative to the HMP group. Compared to the HMP group, the slit3@HMP favored type H vessel formation at the TBI while the slit3-AB@HMP impeded it. According to micro-CT assessment, compared to the HMP group, the slit3@HMP significantly increased the peri-tunnel bone mass while the slit3-AB@HMP significantly reduced the peri-tunnel bone mass. The mice in the slit3@HMP group showed the best gait performance in terms of stance time, stride length, paw print area, and stance pressure. Dynamic laxity measurement and tensile testing showed the slit3@HMP group exhibited significantly reduced laxity displacement and improved failure load and stiffness relative to the other two groups. Collectively, the injection of slit3 could be used to enhance tendon-bone integration, which may be ascribed to modulation of angiogenesis-osteogenesis crosstalk coupled by type H vessels.

Risk Factors for Diabetic Retinopathy in Chinese Patients with Different Diabetes Duration: Association of C-Peptide and BUN/Cr Ratio with Type 2 Diabetic Retinopathy.

Background and Aim: Controlling the risk factors was the most effective strategy to prevent diabetic retinopathy (DR). This study aimed to recognize the risk factors of DR, and explores whether the effect of those factors is modified by diabetes mellitus (DM) duration. Methods: A total of 1058 DM patients with information about DR assessment were included. DR was measured by a complete ophthalmic examination and was classified as having one or more distinct microaneurysms in the eyes. Data from the lab and clinical factors were gathered. Multivariate logistic analysis was used to examine the risk factors, and the best-fitting model was selected by a backward stepwise based on A1C. Results: In the current study, 274 (25.9%) patients developed DR. In the entire subjects, baseline age, the level of C-peptide, and urinary creatinine were all presented as protective effects of DR, whose odds ratios (ORs) and 95% confidence intervals (CIs) were 0.79 (0.62, 0.99), 0.75 (0.61, 0.91), and 0.70 (0.52, 0.93), respectively. Conversely, systolic pressure (SBP), urinary albumin, and BUN/Cr ratio were the important risk factors for DR with ORs (95% CIs) 1.21 (1.01, 1.46), 1.55 (1.30, 1.84), and 1.33 (1.11, 1.59), respectively. In stratification analysis, females with higher SBP would be more likely to develop DR in the short-duration group, while C-peptide and urinary creatinine showed protective effects in the long-duration group. BUN/Cr ratio all presented as a risk factor, with ORs 1.38 (p = 0.041) and 1.33 (p = 0.014) in short- and long-duration groups, respectively. Conclusion: Although renal functions presented a significant association with DR in all DM patients, the risk factors of DR varied widely in different disease-duration subjects. Target strategies to prevent DR should be put forward individually, considering the patient's DM duration. Improving the BUN/Cr ratio may be beneficial to delaying DR.

adducin 1 is essential for the survival of erythroid precursors via regulating p53 transcription in zebrafish.

Adducin 1 (Add1) is known as a membrane cytoskeletal protein, but its nuclear function remains unclear. In this study, we generated add1-deficient zebrafish to investigate its role in hematopoiesis. Lack of add1 impaired both primitive and definitive hematopoiesis, preventing healthy erythrocyte development. RNA sequencing revealed activation of the p53 pathway in add1-depleted erythroblast cells, leading to apoptosis at the 14-somites stage and 24 hpf. Interestingly, partial rescue of the anemic phenotype and apoptosis was observed with p53 insufficiency. Mechanistically, ADD1 was found to regulate promoter activity. These findings demonstrate that Add1 plays a crucial role in zebrafish erythropoiesis, involving the p53-mediated apoptotic pathway, expanding its regulatory role beyond cytoskeletal functions.

Valorization of waste streams and C1 gases for sustainable food nutrients and value-added compounds production: Acetate as a promising intermediate.

Resource recovery from waste streams and C1 gaseous substrates (CO2, CO and CH4) are of extensive interest due to the insufficient utilization and threats to the environment. From a perspective of sustainability, valorization of waste streams and C1 gases into target energy-rich value-added products in a sustainable way offers tempting approaches for simultaneously alleviating the environmental problems and achieving a circular carbon economy, while it still suffers from the complicated compositions of feedstocks or the low solubility of gaseous feeds. Recently, a C2 feedstock-based biomanufacturing serving acetate as potential next-generation platform has received much attention, where different gaseous or cellulosic wastes are recycling into acetate and then be further processed into a wide range of valuable long-chain compounds. The different alternative waste-processing technologies that are being developed to generate acetate from various wastes or gaseous substrates are summarized, in which gas fermentation and electrochemical reduction from CO2 represent the most promising routes for achieving high acetate yield. The recent advances and innovations in metabolic engineering for acetate bioconversion into various bioproducts ranging from food nutrients to value-added compounds were then highlighted. The challenges and promising strategies to reinforce microbial acetate conversion were also proposed, which conferred a new horizon for future food and chemical manufacturing with reduced carbon footprint.

Hepar-on-a-sensor-platform with hybridization chain reaction amplification strategy to intuitively monitor the hepatoxicity of natural compounds.

The irrational use of natural compounds in the treatment of diseases can lead to serious side effects, especially hepatoxicity, and its toxic effects are usually cumulative and imperceptible. Therefore, an accurate sensing platform is urgently needed to monitor the hepatotoxicity of natural compounds. Here, we deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and a thorough validation was adopted to evaluate the bioprinted hepatic constructs. The engineered hepar-platform was then employed to access its biological response toward Emodin (EM) and Triptolide (TP), two typical hepatotoxic natural compounds. Subsequently, we integrated it with a robust fluorescent sensor based on hybridization chain reaction amplification strategy (HCR) to monitor the early hepatotoxic biomarker - glutathione-S-transferase-alpha (GST-α) secreted by this 3D constructs. Our study was the first attempt to construct an accurate hepar-on-a-sensor platform that could effectively detect GST-α for monitoring the hepatoxic effects of natural compounds. The limit of detection of the platform was 0.3 ng ml-1 and the accuracy of this platform was verified by enzyme linked immunosorbent assay. Furthermore, the variation of GST-α induced by EM and TP was consistent with hepatotoxicity studies, thus providing an important application value for evaluating the hepatotoxicity of natural compounds. STATEMENT OF SIGNIFICANCE: 1. We deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and elucidated the essential reasons why hybrid bioinks more suitable for 3D extrusion from biomaterials itself. Also, a thorough validation associated with a series of important proteins and genes involved in liver cell metabolism was adopted to evaluate the bioprinted hepatic constructs accurately 2. Glutathione-S-transferase-alpha is a soluble trace biomarker for acute hepatotoxic injury, the hepatotoxic effects of natural compounds on the secretion of GST-α has not been reported to date. We integrated our 3D hepar-platform with recognition molecules-aptamers and HCR amplification strategy to monitor the variation of GST-α, aiming at developing a robust and stable fluorescent biosensing platform to monitor the hepatoxicity of natural compounds.

Intravoxel incoherent motion diffusion-weighted MRI of renal parenchyma and its clinical significance in patients with untreated acute leukemia: a pilot study.

PURPOSE: To evaluate quantitative parameters derived from intravoxel incoherent motion diffusion-weighted MRI (IVIM) of renal parenchyma in patients with untreated acute leukemia (AL) and analyze its prognostic significance and probable pathological mechanism. METHODS: From March 2019 to November 2021, 67 newly diagnosed AL patients and 67 healthy controls matched in age and sex were recruited. All participants underwent IVIM in the kidneys, and D, D*, f, standard ADC values were measured. The differences of all parameters between AL and controls were analyzed. The relationship between imaging parameters and estimated glomerular filtration rate (eGFR) was studied. Univariable and multivariable analyses were performed to investigate prognostic significance of possible indicators. RESULTS: The f and D value of renal medulla and D value of renal cortex in AL patients were lower than those in the healthy control group (t = - 2.173, t = - 3.463, t = - 2.030, respectively, all P < 0.05). The cortical f, cortical standard ADC, medullary f, and medullary standard ADC were correlated with the eGFR (r = 0.524, r = 0.401, r = 0.415, r = 0.325, respectively, all P < 0.05) in patients with AL. A medullary f value ≤ 9.51% (hazard ratio: 0.282; 95% confidence interval: 0.110, 0.719; P = 0.008) was associated with overall survival in a multivariable analysis. CONCLUSION: The f and standard ADC values in renal parenchyma were the probable imaging markers of renal function in patients with newly diagnosed de novo AL. Lower renal medullary f value was a potential independent predictor for overall survival.

Supramolecular self-assembled AIE molecules are used in the search for target proteins in norcantharidin.

Norcantharidin (NCTD), a demethylated derivative of cantharidin, is an anticancer active component in traditional Chinese medicine. At present, the main methods for finding its target proteins are pharmacological methods and biophysical screening, which cannot achieve the purpose of efficient and accurate screening. Here we established a new analytical method for specific fishing and assisted imaging for norcantharidin target proteins. For the AIE supramolecule probe, the benzophenone azide (BPA) fluorescent nanoparticles with strong AIE properties were encapsulated in biocompatible DSPE-PEG that covalently coupled with NCTD (named BPA@NCTD NPs). The target proteins of NCTD can be captured by BPA@NCTD NPs, and then be detected to investigate the potential signaling pathways. The screened differential proteins were analysed through the protein and signaling pathway database, and multiple signaling pathways were obtained and verified. The mechanism of norcantharidin in inhibiting the migration and invasion of A549 cells through the P53 signaling pathway was confirmed by Western blot experiments. Our research showed that AIE supramolecule probe BPA@NCTD NPs has the dual functions of specific screening of A549 cells target proteins and biological imaging, which not only offers a good anti-fluorescence quenching ability for the dynamic imaging process of NCTD, but also provides a novel and efficient specific method for efficient analysis of target proteins and signal pathways.