Magnetic Soft Microrobot Design for Cell Grasping and Transportation.

Manipulating cells at a small scale is widely acknowledged as a complex and challenging task, especially when it comes to cell grasping and transportation. Various precise methods have been developed to remotely control the movement of microrobots. However, the manipulation of micro-objects necessitates the use of end-effectors. This paper presents a study on the control of movement and grasping operations of a magnetic microrobot, utilizing only 3 pairs of electromagnetic coils. A specially designed microgripper is employed on the microrobot for efficient cell grasping and transportation. To ensure precise grasping, a bending deformation model of the microgripper is formulated and subsequently validated. To achieve precise and reliable transportation of cells to specific positions, an approach that combines an extended Kalman filter with a model predictive control method is adopted to accomplish the trajectory tracking task. Through experiments, we observe that by applying the proposed control strategy, the mean absolute error of path tracking is found to be less than 0.155 mm. Remarkably, this value accounts for only 1.55% of the microrobot's size, demonstrating the efficacy and accuracy of our control strategy. Furthermore, an experiment involving the grasping and transportation of a zebrafish embryonic cell (diameter: 800 µm) is successfully conducted. The results of this experiment not only validate the precision and effectiveness of the proposed microrobot and its associated models but also highlight its tremendous potential for cell manipulation in vitro and in vivo.

Toward Intelligent Display with Neuromorphic Technology.

In the era of the Internet and the Internet of Things, display technology has evolved significantly toward full-scene display and realistic display. Incorporating "intelligence" into displays is a crucial technical approach to meet the demands of this development. Traditional display technology relies on distributed hardware systems to achieve intelligent displays but encounters challenges stemming from the physical separation of sensing, processing, and light-emitting modules. The high energy consumption and data transformation delays limited the development of intelligence display, breaking the physical separation is crucial to overcoming the bottlenecks of intelligence display technology. Inspired by the biological neural system, neuromorphic technology with all-in-one features is widely employed across various fields. It proves effective in reducing system power consumption, facilitating frequent data transformation, and enabling cross-scene integration. Neuromorphic technology shows great potential to overcome display technology bottlenecks, realizing the full-scene display and realistic display with high efficiency and low power consumption. This review offers a comprehensive summary of recent advancements in the application of neuromorphic technology in displays, with a focus on interoperability. This work delves into its state-of-the-art designs and potential future developments aimed at revolutionizing display technology.

Performance Prediction and Heating Parameter Optimization of Organic-Rich Shale In Situ Conversion Based on Numerical Simulation and Artificial Intelligence Algorithms.

In situ conversion technology is a green and effective way to realize the development of organic-rich shale. Supercritical CO2 can be used as a good heating medium for shale in situ conversion. Numerical simulation is an important means to explore the shale in situ conversion process, but it requires a lot of time and computational cost for in situ conversion simulation under different working conditions. Therefore, a computational framework for rapid prediction of shale in situ conversion development performance and heating parameter optimization is proposed by coupling artificial neural network (ANN) and particle swarm optimization (PSO). The results indicated that kerogen pyrolysis and hydrocarbon product release mainly occurred within 2 years of shale in situ conversion. The production curves of pyrolysis hydrocarbon obviously slowed after in situ conversion for 2 years. The database was constructed by a large number of in situ conversion simulations, and Pearson correlation analysis and the random forest method were adopted to obtain seven main controlling factors affecting reservoir temperature and hydrocarbon production. The determination coefficient of the obtained ANN-based prediction models is higher than 97%, and the mean square error (MSE) is lower than 0.3%. The basic reservoir case can choose to inject 350-450 °C supercritical CO2 (Sc-CO2) fluid with a rate of 600 m3/day to obtain a more promising development effect. The heating parameter optimization for three typical reservoir cases using PSO was performed, and reasonable injection temperature and injection rate were obtained. It realized accurate development prediction and rapid heating parameter optimization, which helps the effective application of shale in situ conversion development design.

Room-temperature low-threshold avalanche effect in stepwise van-der-Waals homojunction photodiodes.

Avalanche or carrier-multiplication effect, based on impact ionization processes in semiconductors, has a great potential for enhancing the performance of photodetector and solar cells. However, in practical applications, it suffers from high threshold energy, reducing the advantages of carrier multiplication. Here, we report on a low-threshold avalanche effect in a stepwise WSe2 structure, in which the combination of weak electron-phonon scattering and high electric fields leads to a low-loss carrier acceleration and multiplication. Owing to this effect, the room-temperature threshold energy approaches the fundamental limit, Ethre ≈ Eg, where Eg is the bandgap of the semiconductor. Our findings offer an alternative perspective on the design and fabrication of future avalanche and hot-carrier photovoltaic devices.

Synergistic effects of biochar addition and filtration mode optimization on mitigating membrane fouling in high-solid anaerobic membrane bioreactors.

In this study, a high-solid anaerobic membrane bioreactor was established for treating food waste, and membrane fouling rates were regulated through multivariate modulation. The anaerobic membrane bioreactor operated stably at a high organic loading rate of 28.75 gCOD/L/d achieved a methane production rate of 8.03 ± 0.61 L/L/d. Experimental findings revealed that the most effective control of membrane fouling was achieved at a filtration- relaxation ratio (F/R) of 10/90 s. This indicates that a higher relaxation frequency provided improved the mitigation of membrane fouling. Compared with single F/R modulation, the combined modulation of biochar and F/R provided enhanced control over membrane fouling. Moreover, the addition of biochar altered the sludge properties of the reactor, thereby preventing the formation of a dense cake layer. Additionally, biochar enhanced the sheer force of the fluid on the membrane surface and facilitated the separation of pollutants during the relaxation stage, thereby contributing to improved control of membrane fouling.

Enantioselective Divergent Syntheses of Diterpenoid Pyrones.

Capitalizing a synergy between late-stage C(sp3)-H alkynylation and a series of transition metal-catalyzed alkyne functionalization reactions, we reported herein enantioselective divergent synthesis of 10 diterpenoid pyrones within 14-16 steps starting from chiral pool enoxolone, including the first enantioselective synthesis of higginsianins A, B, D, E, and metarhizin C. Our synthesis also highlights an unprecedented biomimetic oxidative rearrangement of α-pyrone into 3(2H)-furanone, as well as applications of Echavarren C(sp3)-H alkynylation reaction and Toste chiral counterion-mediated Au-catalyzed intramolecular allene hydroalkoxylation in natural product synthesis.

Phlorizin, an Important Glucoside: Research Progress on Its Biological Activity and Mechanism.

Phlorizin, as a flavonoid from a wide range of sources, is gradually becoming known for its biological activity. Phlorizin can exert antioxidant effects by regulating the IL-1ß/IKB-α/NF-KB signaling pathway. At the same time, it exerts its antibacterial activity by reducing intracellular DNA agglutination, reducing intracellular protein and energy synthesis, and destroying intracellular metabolism. In addition, phlorizin also has various pharmacological effects such as antiviral, antidiabetic, antitumor, and hepatoprotective effects. Based on domestic and foreign research reports, this article reviews the plant sources, extraction, and biological activities of phlorizin, providing a reference for improving the clinical application of phlorizin.

Enantioselective Synthesis of the 1,3-Dienyl-5-Alkyl-6-Oxy Motif: Method Development and Total Synthesis.

The 1,3-dienyl-5-alkyl-6-oxy motif is widely found in various types of bioactive natural products. However, present synthesis is mainly non-asymmetric which relied upon different olefination or transition metal-catalyzed cross-coupling reactions using enantioenriched precursors. Herein, based upon a newly developed enantioselective α-alkylation of conjugated polyenoic acids, a variety of 1,3-dienyl-5-alkyl-6-oxy motif (with E-configured internal olefin) was generated as the corresponding α-adducts in a highly enantioselective and diastereoselective manner. Utilizing 1,3-dienyl-5-alkyl-6-oxy motif as key intermediates, we further demonstrated their synthetic potential by expedient total syntheses of three types of natural products (glutarimide antibiotics, α-pyrone polyketides and Lupin alkaloids) within 4-7 steps.

Effects of Guizhi and Erxian Decoction on menopausal hot flashes: insights from the gut microbiome and metabolic profiles.

AIMS: To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes. METHODS AND RESULTS: 16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota. GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing l(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition. CONCLUSIONS: Our study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut-brain axis in hot flashes.

Modified Guo-Min decoction ameliorates PM2.5-induced lung injury by inhibition of PI3K-AKT and MAPK signaling pathways.

BACKGROUND/PURPOSE: Exposure to particles with an aerodynamic diameter of ≤2.5 µm (PM2.5) increased various lung diseases, which lack effective treatment. Massive evidence links PM2.5 to the development of allergic lung diseases like asthma. Modified Guo-Min Decoction (MGMD) is a traditional Chinese formula for allergic diseases. However, whether MGMD could improve PM2.5-induced lung injury and the underlying mechanism remain unclear and we aimed to explore. STUDY DESIGN/METHODS: Male Wistar rats (200-220 g) were intratracheally instilled of PM2.5 suspension daily for 4 weeks to establish PM2.5-induced lung injury model. MGMD (2.1 g/kg) treatment by gavage was started 1 week before, at the same time or 1 week after the instillation of PM2.5 suspension, namely the pre-, sync- or post-administration groups. HE and Masson staining were used to observe morphological changes. Immunohistochemistry staining was used to detect macrophage and neutrophil infiltration. The levels of inflammatory cytokines in the bronchoalveolar lavage fluid were detected by ELISA. The main components of MGMD were detected by UHPLC-LTQ-Orbitrap MSn. Network pharmacology was used to identify the key targets mediating the effect of MGMD in treating PM2.5-induced lung injury. Changes in the expression of target proteins were examined by western blot. In-vitro experiments were carried out in Beas2b cells to evaluate the protective effect and mechanism of MGMD against PM2.5 induced injury. RESULTS: Exposure to PM2.5 suspension resulted in disarrangement of tracheal epithelium, neutrophil and M1 macrophage infiltration and collagen deposition, and significantly increased IgE, IL-1ß and IL-17 secretion and NLRP3 expression, which were inhibited by MDMD treatment and pre-MGMD treatment showed the best effect. By UHPLC-LTQ-Orbitrap MSn, 46 main compounds were identified in MGMD. Using network pharmacology approach, we found MGMD attenuate PM2.5-induced lung damage by targeting 216 genes, and PPI network, GO and KEGG analysis all indicated that PI3K-AKT and MAPK pathways were important. Western blot showed that PM2.5 suspension exposure increased PI3K, AKT, ERK and JNK phosphorylation, which were reversed by MGMD intervention significantly. In vitro, the viability of Beas2b cells was significantly decreased after PM2.5 suspension exposure, and was obviously upregulated after MGMD-containing serum or LY294002 treatment. CONCLUSION: The present study demonstrated that MGMD could improve PM2.5-induced lung injury through reducing inflammation and pulmonary fibrosis, which was probably mediated by inhibition of the PI3K-AKT and MAPK signaling pathways, and NLRP3 inflammasome. The results of this study support and provide scientific evidence for the clinical application of MGMD on PM2.5-induced lung injury. Pre-treatment, sync-treatment, and post-treatment is the highlight of this study.

Knockdown of LOX-1 ameliorates bone quality and generation of type H blood vessels in diabetic mice.

Our previous studies have shown that lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) is expressed in liver sinusoidal endothelial cells, and oxidized low-density lipoprotein induces liver sinusoidal dysfunction and defenestration through the LOX-1/ROS/NF-kB pathway, revealing that LOX-1 can mediate liver sinusoidal barrier function, involved in the regulation of non-alcoholic fatty liver disease. Here, we investigated whether, in the context of bone metabolic diseases, LOX-1 could affect bone quality and type H blood vessels in diabetic mice. We used db/db mice as model and found that LOX-1 knockdown can ameliorate bone quality and type H blood vessel generation in db/db mice. This further verifies our hypothesis that LOX-1 is involved in the regulation of bone quality and type H blood vessel homeostasis, thus inhibiting osteoporosis progression in db/db mice.

Mir-142-3P regulates MAPK protein family by inhibiting 14-3-3η to enhance bone marrow mesenchymal stem cells osteogenesis.

Clinical studies have found 14-3-3η to be associated with osteoporosis through undefined mechanisms. We aimed to investigate the role of 14-3-3η in osteoporosis and its potential associations with miRNAs. The Gene Expression Omnibus(GEO) and Human Protein Atlas 1 databases were analyzed to examine both the mRNA and protein expression of 14-3-3η in OP. Gene enrichment analyses were performed to explore the underlying mechanism of 14-3-3η based on DAVID. miRWalk was used to predict the associated miRNAs. The statistics were analysed by R software and SPSS software. 14-3-3η was overexpressed and knock down expressed in BMSCs by lentiviral vector transfecting. And BMSCs were induced by hypoxia. qRT-PCR and Western-Blot verified the expression of mRNA and protein. Scratch assay detected the migration of osteocytes. Co-immunoprecipitation and luciferase assay studied the 14-3-3η targeted protein and miRNA. overexpression and knock down of miRNA to verify the relationship of 14-3-3η and target genes. The 14-3-3η mRNA expression level was low in patients with osteoporosis, as corroborated by immunohistochemical staining images. Functional analyses revealed enrichment of the MAPK-associated cascade. 14-3-3η was correlated with MAPK family proteins and five key miRNAs, including mir-142-3p. In addition, 14-3-3η knockdown in BMSCs increased the mRNA and protein expression levels of Hif-α, VEGF, BMP-2, OPN, OST, and Runx2, and enhanced the cells migration ability. Under hypoxic conditions, Hif-α and BMP-2 protein expression levels were upregulated, whereas those of 14-3-3η and MAPK3 were downregulated. Co-immunoprecipitation experiments showed decreased binding of 14-3-3η to MAPK3. 14-3-3η knockdown produced the same results as hypoxia induction. Adding caspase3 inhibitor and knocking down 14-3-3η again prevented MAPK3 cleavage by caspase3 and inhibited BMP-2 expression. Moreover, under hypoxic conditions, miR-142-3P expression was upregulated and luciferase assays revealed 14-3-3η as its target gene. miR-142-3P overexpression decreased mRNA and protein levels of 14-3-3η and MAPK3, while increasing BMP-2 expression. miR-142-3P knockdown reversed these results. BMSC osteogenesis was suppressed by 14-3-3η, whereas miRNA-142-3p promoted it through the inhibition of 14-3-3η.

The identification of N6-methyladenosine-related miRNAs predictive of hepatocellular carcinoma prognosis and immunotherapy efficacy.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high degree of malignancy and poor prognosis. N6-methyladenosine (m6A) modifications and microRNAs (miRNAs) play pivotal roles in tumorigenesis and development. However, the role of m6A-related miRNAs in HCC has not been clarified yet. This study aimed to identify the role of m6A-miRNAs in HCC prognosis through bioinformatics analysis. METHODS: The clinicopathological information and RNA sequencing data of 369 HCC tumor tissues and 49 tumor-adjacent tissues were downloaded from the TCGA database. A total of 23 m6A regulators were extracted to evaluated the m6A-related miRNAs using Pearson's correlation analysis. Then, we selected prognosis-related m6A-miRNAs using a univariate Cox regression model and used the consensus cluster analysis to explore the characteristics of the m6A-miRNAs. The coefficient of the least absolute shrinkage and selection operator (LASSO) Cox regression was applied to construct a prognostic risk score model. The receiver operated characteristic (ROC) analysis was applied to evaluate the prognostic value of the signature. The biological functions of targeted genes were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Then, to validate the potential predictive value for prognosis, the miRNA expression profiles from the GSE76903 and GSE6857 were used. Single sample Gene Set Enrichment Analysis (ssGSEA) and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) were applied to assess the immune microenvironment of HCC. Additionally, a meta-analysis was used to verify the prognostic value of the m6A-microRNAs. RT-PCR was applied to validated the expression of miRNAs in HCC tissues. Cell viability, transwell assay and RNA m6A dot blot assays of HCC cells was applied to access the function of miR-17-5p. RESULTS: The expression of 48 m6A-related miRNAs was identified and 17 prognostic m6A-miRNAs was discovered. The expression profile of those 17 miRNAs was divided into three clusters, and these clusters were associated with the tumor microenvironment (TME) and prognosis. The nine m6A-related miRNA signature was associated with the prognosis of HCC, the AUC of the ROC was 0.771(TCGA dataset), 0.788(GSE76903) and 0.646(GSE6857). The TME and the expression of immune checkpoint molecules were associated with the risk score. The meta-analysis also validated the prognostic value of the m6A-related miRNAs (miR182-5p (HR:1.58, 95%CI:1.04-2.40) and miR-17-5p (HR:1.58, 95%CI: 1.04-2.40)). The expression of miR-17-5p was upregulated in HCC tissues and miR-17-5p showed an oncogenic role in HCC cells. CONCLUSION: The clinical innovation is the use of m6A-miRNAs as biomarkers for predicting prognosis regarding immunotherapy response in HCC patients.

RIOK3 potentially regulates osteogenesis-related pathways in ankylosing spondylitis and the differentiation of bone marrow mesenchymal stem cells.

RNA-binding proteins (RBPs), which are key effectors of gene expression, play critical roles in inflammation and immune regulation. However, the potential biological function of RBPs in ankylosing spondylitis (AS) remains unclear. We identified differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of five patients with AS and three healthy persons by RNA-seq, obtained differentially expressed RBPs by overlapping DEGs and RBPs summary table. RIOK3 was selected as a target RBP and knocked down in mouse bone marrow mesenchymal stem cells (mBMSCs), and transcriptomic studies of siRIOK3 mBMSCs were performed again using RNA-seq. Results showed that RIOK3 knockdown inhibited the expression of genes related to osteogenic differentiation, ribosome function, and ß-interferon pathways in mBMSCs. In vitro experiments have shown that RIOK3 knockdown reduced the osteogenic differentiation ability of mBMSCs. Collectively, RIOK3 may affect the differentiation of mBMSCs and participate in the pathogenesis of AS, especially pathological bone formation.

Discovery of two ent-atisane diterpenoid lactones with AChE inhibitory activity from the roots of Euphorbia fischeriana.

Euphorlactone A (1), a rare rearranged ent-atisane norditerpenoid with an undescribed 3-nor-2,4-olide-ent-atisane scaffold, and euphorlactone B (2), a new ent-atisane diterpenoid with an unprecedented seven-membered lactone ring C, were isolated from the roots of Euphorbia fischeriana. Their planar structures with absolute configurations were extensively elucidated by analysis of 1D and 2D NMR data, electronic circular dichroism (ECD) calculations, Rh2(OCOCF3)4-induced ECD curves, and single-crystal X-ray diffraction. Euphorlactone A (ELA) showed a remarkable AChE (acetylcholinesterase) inhibitory activity (IC50 = 2.13 ± 0.06 µM and Ki = 0.058 µM), which was five times stronger than that of the positive control (rivastigmine, IC50 = 12.46 ± 0.82 µM), and further in vitro enzyme inhibition kinetic analysis and molecular docking studies were performed to investigate the AChE inhibitory mechanism.

A novel colchicine-myricetin heterozygous molecule: design, synthesis, and effective evaluations on the pathological models of acute lung injury in vitro and in vivo.

Acute lung injury (ALI) is an inflammatory condition and there are no effective treatments. A novel new compound----colchicine-myricetin hybrid (CMyrH) was herein designed and synthesized. To evaluate the activity of CMyrH in ALI, we used a bleomycin (BLM) induced BEAS-2B injury model in vitro and established a well-recognized rat model of BLM-induced lung injury in vivo. The results demonstrated that colchicine-myricetin hybrid protected BEAS-2B cells against BLM-induced cell injury in an increased dose manner, and reduced wet/dry weight ratio, histological scoring, and inflammation cytokines IL-1ß, IL-6, IL-18, and TNF-α levels of lung tissue of the rats. Furthermore, we found colchicine-myricetin hybrid inhibited caspase-1, ASC, GSDMD, and NLRP-3 expression in vivo. Meanwhile, we used molecular docking to analyze the binding mode of colchicine-myricetin hybrid and human neutrophil elastase (HNE), it revealed that colchicine-myricetin hybrid showed strong binding affinity toward human neutrophil elastase when compared to its parent molecules. In conclusion, It is suggested that colchicine-myricetin hybrid antagonized acute lung injury by focusing on multi-targets via multi-mechanisms, and might be served as a potential therapeutic agent for acute lung injury.

Quantitative Analysis of Natural Gas Diffusion Characteristics in Tight Oil Reservoirs Based on Experimental and Numerical Simulation Methods.

As an important mechanism in gas injection development, the diffusion characteristics of natural gas in tight reservoirs are important in the dynamic prediction of the development effect and optimization of injection-production parameters. In this paper, a high-pressure and high-temperature oil-gas diffusion experimental device was built, which was used to study the effects of the porous medium, pressure, permeability, and fracture on oil-gas diffusion under tight reservoir conditions. Two mathematical models were used to calculate the diffusion coefficients of natural gas in bulk oil and cores. Besides, the numerical simulation model was established to study the diffusion characteristics of natural gas in gas flooding and huff-n-puff, and five diffusion coefficients were selected based on experimental results for simulation study. The remaining oil saturation of grids, the recovery of single layers, and the distribution of CH4 mole fraction in oil were analyzed based on the simulation results. The experimental results show that the diffusion process can be divided into three stages: the initial stage of instability, the diffusion stage, and the stable stage. The absence of medium, high pressure, high permeability, and the existence of fracture are beneficial to natural gas diffusion, which can also reduce the equilibrium time and increase the gas pressure drop. Furthermore, the existence of fracture is beneficial to the early diffusion of gas. The simulation results show that the diffusion coefficient has a greater influence on the oil recovery of huff-n-puff. For gas flooding and huff-n-puff, the diffusion features both perform such that a high diffusion coefficient results in a close diffusion distance, small sweep range, and low oil recovery. However, a high diffusion coefficient can achieve high oil washing efficiency near the injecting well. The study is helpful to provide theoretical guidance for natural gas injection in tight oil reservoirs.

Enhanced Anti-Biofouling Properties of BWRO Membranes via the Deposition of Poly (Catechol/Polyamine) and Ag Nanoparticles.

The surface modification of reverse osmosis (RO) membranes to improve their anti-biofouling properties is gaining increased attention. Here, we modified the polyamide brackish water reverse osmosis (BWRO) membrane via the biomimetic co-deposition of catechol (CA)/tetraethylenepentamine (TEPA) and in situ growth of Ag nanoparticles. Ag ions were reduced into Ag nanoparticles (AgNPs) without extraneous reducing agents. The hydrophilic property of the membrane was improved, and the zeta potential was also increased after the deposition of poly (catechol/polyamine) and AgNPs. Compared with the original RO membrane, the optimized PCPA3-Ag10 membrane showed a slight reduction in water flux, and the salt rejection declined, but enhanced anti-adhesion and anti-bacterial activities were observed. The FDRt of the PCPA3-Ag10 membranes during the filtration of BSA, SA and DTAB solution were 5.63 ± 0.09%, 18.34 ± 0.33% and 34.12 ± 0.15%, respectively, much better than those of the original membrane. Moreover, the PCPA3-Ag10 membrane exhibited a 100% reduction in the number of viable bacteria (B. subtilis and E. coli) inoculated on the membrane. The stability of the AgNPs was also high enough, and these results verify the effectiveness of poly (catechol/polyamine) and the AgNP-based modification strategy for the control of fouling.

Incidence of acute kidney injury after hematopoietic stem cell transplantation in children: a systematic review and meta-analysis.

While acute kidney injury (AKI) has been reported after hematopoietic stem cell transplantation (HCT) in children, the incidence of this condition in the pediatric population has not been fully addressed. To assess the incidence of pediatric AKI after HCT treatment,we conducted a systematic literature review. Databases PubMed, Embase, Cochrane Library, and WOS were searched as of June 2022 to identify studies on the incidence and the risk of death in AKI children undergoing HCT. Random effects and generic inverse variance methods were used, and effect estimates were subsequently derived from individual studies. Twelve cohort studies with 2 159 HCT cases were included in this analysis. The combined estimated incidence of AKI and severe AKI (stage AKI III) was 51% (95% confidence interval (CI) 39-64%) and 12% (95%CI 4-24%), respectively. The estimated incidence of AKI based on RIFLE (pRIFLE), AKIN, and KDIGO criteria was 61% (95%CI 40-82% score I 95.1%), 64% (95%CI 49-79% score I 90.4%), and 51% (95%CI 2-100% score 99.0%), respectively. However, we found no significant correlation between the years of publication of the included studies and the incidence of AKI.  Conclusions: AKI affects approximately half of the children after HCT. With the advancements in medical techniques, it is expected that AKI in this population will decrease gradually. What is Known: • Hematopoietic stem cell transplantation is recognized as a treatment for malignant and non-malignant diseases in children. • Hematopoietic stem cell transplantation causes acute kidney injury in children. What is New: • This metanalysis showed that the overall frequency of post-HCT AKI in children is 51%. • The frequency of severe AKI after HCT was found to be 12%.

Prognostic and Immunological Roles of CES2 in Breast Cancer and Potential Application of CES2-Targeted Fluorescent Probe DDAB in Breast Surgery.

Purpose: The expression and function of CES2 in breast cancer (BRCA) has not been fully elucidated. The purpose of this study was to investigate its clinical significance in BRCA. Patients and Methods: Bioinformatics analysis tools and databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, SURVIVAL packages, STRING database, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene set variation analysis (GSVA), and Tumor Immunity Estimation Resource (TIMER), were utilized to measure the expression level and clarify the clinical significance of CES2 in BRCA. In addition, we verified the expression level of CES2 in BRCA at the cellular and tissue levels by Western blot, immunohistochemistry (IHC) and real-time fluorescence quantitative PCR assays. Furthermore, DDAB is the first reported near-infrared fluorescent probe that can be used to monitor CES2 in vivo. We applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time and verified its physicochemical properties and labeling sorting ability by CCK-8, cytofluorimetric imaging, flow cytometry fluorescence detection, and isolated human tumor tissue imaging assays. Results: The expression of CES2 was higher in normal tissues than that in BRCA tissues. Patients with lower CES2 expression in the BRCA T4 stage had a poorer prognosis. Finally, we applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time, which was demonstrated to have good cellular imaging performance with low biological toxicity in BRCA cells and ex vivo human breast tumor tissue models. Conclusion: CES2 can be considered a potential biomarker to predict the prognosis of breast cancer at stage T4 and might contribute to the development of immunological treatment strategies. Meanwhile, CES2 is able to distinguish between breast normal and tumor tissues, the CES2-targeting NIR fluorescent probe DDAB may have potential for surgical applications in BRCA.