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Since its discovery, blaNDM-5has spread widely amongst Escherichia colistrains in clinical patients, causing carbapenem resistance. Here we report the complete genome sequence of an NDM-5-producing E. colistrain isolated from the faecal sample of a healthy individual in Hangzhou, China.

Microbubbles have attracted considerable attention due to their distinctive properties, such as large surface area, inherent self-compression, and exceptional mass transfer efficiency. These features render microbubbles valuable across a diverse range of industries, such as water treatment, mineral flotation, and the food industry. While several methods for microbubble generation exist, the gas–liquid membrane dispersion technique emerges as a reproducible and efficient alternative. Nevertheless, conventional approaches struggle to achieve active in situcontrol of bubble generation. In this study, we introduce an electrostatically responsive liquid gating system (ERLGS) designed for the active management of microbubble production. Utilizing electric fields and anionic surfactants, our system showcases the capability to dynamically regulate bubble size by manipulating the solid–liquid adsorption. Experiments confirm that this active control relies on the electrostatic adsorption and desorption of anionic surfactants, thereby regulating the interactions among the solid–liquid–gas interfaces. Our research elucidates the ERLGS's ability of precisely controlling the generation of bubbles in situ, enabling nearly one-order-of-magnitude change in bubble size, underscoring its applicability in various fields.Keywords: Liquid gating system; Electrostatic response; Anionic surfactants; Adsorption and desorption; Microbubbles.

AbstractIncreasing evidence shows that maternal hyperglycemia inhibits cardiomyocyte (CM) proliferation and promotes cell apoptosis during fetal heart development, which leads to cardiac dysplasia. Accumulating evidence suggests that the overexpression of miR-21 in CMs has a protective role in cardiac function. Therefore, we investigated whether miR-21 can rescue CM injury caused by high glucose. First, we performed biological function analysis of miR-21-5p overexpression in H9c2 cells treated with high glucose. We found that the proliferation of H9c2 cells treated with high glucose decreased significantly and was rescued after overexpression of miR-21-5p. CCK-8 and EdU incorporation assays were performed to assess cell proliferation. The cell proliferation of the miR-21-5p mimic transfection group was improved compared with that of the NC mimic group (*p< 0.05, miR-21-5p mimics vs. NC mimics) when the proliferation of H9c2 cells was reduced by high glucose (****p< 0.0001, high glucose (HG) vs. normal glucose (NG)). Then, we verified the targeted and negative regulation of miR-21-5p on Rhobusing a dual-luciferase activity assay and RT-qPCR, respectively. We further demonstrated that miR-21-5p regulates Rhobto rescue the inhibition of CM proliferation induced by high glucose. The CCK-8 results showed that the cell proliferation of the siRNA-Rhob group was higher than that of the NC mimic group (***p< 0.001) and that of the cotransfection group with Up-Rhob plasmids and miR-21-5p mimics was lower than that of the miR-21-5p mimic group (*p< 0.05). Conclusion: Overexpression of miR-21-5p rescues the inhibition of high glucose-induced CM proliferation through regulation of Rhob.

Purpose:The aim of this study was to analyze the effects of various genetic polymorphisms and clinical factors on tacrolimus (TAC) concentration in the convalescence period (CP) and stabilization period (SP) post-liver transplantation. Patients & methods:A total of 13 SNPs were genotyped in 97 Chinese liver transplant recipients. Associations between SNPs and TAC trough blood concentration/dose ratio (C0/D) were analyzed using different genetic models in both CP and SP. Results:Only five SNPs were significantly associated with TAC log (C0/D) in the CP, and none showed a significant association in the SP. We identified rs15524 (CYP3A5), rs9200 (C6), albumin and creatinine as independent predictors of TAC C0/D in the CP. Furthermore, a final model in the CP explained a total of 30.5% TAC variation. Conclusion:Our study results suggest that in the early stages post-transplantation surgery, recipients’ genetic and clinical factors exert a short-term impact on TAC metabolism that gradually decreases with time.

A 2D van der Waals (vdW) magnet can get rid of the constraints of lattice matching and compatibility and then create a variety of vdW heterostructures, which provides a opportunity for spintronic devices. However, the ability to reliably exfoliate large, high-quality vdW ferromagnetic Fe3GeTe2(FGT) nanoflakes in scaled-up production is severely limited. Herein, an efficient and stable three-stage sonication-assisted liquid-phase exfoliation was developed for mass preparation of high-structural-integrity few- and single-layer FGT nanoflakes with a greatly enhanced intrinsic exchange bias. The three stages include slicing crystals, weakening interlayer vdW forces, and using ultrasonic cavitation. The highest yield of FGT nanoflakes is 22.3 wt % with single layers accounting for 6%. The size is controllable, and several micrometers, tens of micrometers, and a maximum of 103 μm are available. The 200 mg level output has overcome the limitations of mechanical exfoliation and molecular beam epitaxy in economically amplificated production. An intrinsic exchange bias is observed in the restacked nanoflakes due to the magnetic proximity on the interface of the FGT/natural surface oxide layer. The material reaches 578 Oe (2 K) and 2300 Oe after further oxidation, at least 250% higher than other precisely tailored vdW magnetic heterostructures. In addition, the unusual semiconductivity of the liquid-phase exfoliated FGT nanoflakes is reported. This work skillfully utilizes oxidation to enhance the potential of FGT for large-scale spintronics, optoelectronics, efficient data storage, and various extended applications, and it is beneficial for exfoliating other promising magnetic vdW materials.

A high-quality Fe3GeTe2single crystal with good electrical, magnetic, and electromagnetic wave absorption and shielding properties was prepared in a large quantity (10 g level) by solid-phase sintering and recrystallization method, which would promote its in-depth research and practical application. It has good room-temperature electrical properties with a mobility of 42 cm2/V·s, a sheet (bulk) carrier concentration of +1.64 × 1018/cm2(+3.28 × 1020/cm3), and a conductivity of 2196.35 S/cm. Also, a Curie temperature of 238 K indicates the high magnetic transition temperature and a paramagnetic Curie temperature of 301 K shows the large ferromagnetic–paramagnetic transition zone induced by the residual short-range ferromagnetic domains. Particularly, Fe3GeTe2is in a loosely packed state when used as a loss agent; the electromagnetic wave absorption with a reflection loss of −34.7 dB at 3.66 GHz under thin thickness was shown. Meanwhile, the absorption band can be effectively regulated by varying the thickness. Moreover, Fe3GeTe2in a close-packed state exhibits terahertz shielding values of 75.1 and 103.2 dB at very thin thicknesses of 70 and 380 μm, and the average shielding value is higher than 47 dB, covering the entire bandwidth from 0.1 to 3.0 THz. Furthermore, by using Fe3GeTe2as a patch, the wideband radar cross-section can be effectively reduced by up to 33 dBsm. Resultantly, Fe3GeTe2will be a promising candidate in the electromagnetic protection field.

Two-dimensional (2D) materials are candidates for use in advanced molecular separation and water treatment. Among them, MXenes are cutting-edge two-dimensional (2D) materials with favorable properties such as high hydrophilicity, adjustable interlayer spacing, high mechanical strength, and structural stability. Therefore, they can be used to construct advanced lamellar membranes to ensure enhanced separation performance of modified membranes. Here, we prepared novel stable lamellar membranes through electrostatic attraction between polycation polyethyleneimine (PEI) and a negatively charged MXene, with hydrogen bond formation between their functional groups. By changing the pH of the suspension, the interlayer d-spacing of the prepared membrane could be altered to achieve precise molecular separation and ultrahigh organic solvent penetration. Furthermore, inserting PEI into the interlayer d-spacing of the membrane did not hinder the passage of water molecules. The prepared pH = 2-MXene-PEI membrane for dyes larger than 1.5 nm exhibited a rejection rate of greater than 96%, and the pH = 10-MXene-PEI membrane had a rejection rate of greater than 96% for dyes larger than 1.6 nm. In addition, the optimized MXene-PEI membranes showed channel stability. In this work, high-performance, stable, 2D MXene-PEI membranes with tunable nanochannels were developed. These membranes have great potential for use in precise molecular separation applications.

Since the huge success of bone marrow transplantation technology in clinical practice, hematopoietic stem cells (HSCs) have become the gold standard for defining the properties of adult stem cells (ASCs). Here, we describe the “self-renewal, multi-lineage differentiation, apoptosis, rest, and trafficking” or “SMART” model, which has been developed based on data derived from studies of HSCs as the most well-characterized stem cell type. Given the potential therapeutic applications of ASCs, we delineate the key characteristics of HSCs using this model and speculate on the physiological relevance of stem cells identified in other tissues. Great strides are being made in understanding the biology of ASCs, and efforts are now underway to develop safe and effective ASC-based therapies in this emerging area.

Total body irradiation (TBI) is commonly used in host conditioning regimens for human hematopoietic stem cell (HSC) transplantation to treat various hematological disorders. Exposure to TBI not only induces acute myelosuppression and immunosuppression, but also injures the various components of the HSC niche in recipients. Our previous study demonstrated that radiation-induced bystander effects (RIBE) of irradiated recipients decreased the long-term repopulating ability of transplanted mouse HSCs. However, RIBE on transplanted human HSCs have not been studied. Here, we report that RIBE impaired the long-term hematopoietic reconstitution of human HSCs as well as the colony-forming ability of human hematopoietic progenitor cells (HPCs). Our further analyses revealed that the RIBE-affected human hematopoietic cells showed enhanced DNA damage responses, cell-cycle arrest, and p53-dependent apoptosis, mainly because of oxidative stress. Moreover, multiple antioxidants could mitigate these bystander effects, though at different efficacies in vitro and in vivo. Taken together, these findings suggest that RIBE impair human HSCs and HPCs by oxidative DNA damage. This study provides definitive evidence for RIBE on transplanted human HSCs and further justifies the necessity of conducting clinical trials to evaluate different antioxidants to improve the efficacy of HSC transplantation for the patients with hematological or nonhematological disorders.

Total body irradiation (TBI) is commonly used in host conditioning regimens for human hematopoietic stem cell (HSC) transplantation to treat various hematological disorders. Exposure to TBI not only induces acute myelosuppression and immunosuppression, but also injures the various components of the HSC niche in recipients. Our previous study demonstrated that radiation-induced bystander effects (RIBE) of irradiated recipients decreased the long-term repopulating ability of transplanted mouse HSCs. However, RIBE on transplanted human HSCs have not been studied. Here, we report that RIBE impaired the long-term hematopoietic reconstitution of human HSCs as well as the colony-forming ability of human hematopoietic progenitor cells (HPCs). Our further analyses revealed that the RIBE-affected human hematopoietic cells showed enhanced DNA damage responses, cell-cycle arrest, and p53-dependent apoptosis, mainly because of oxidative stress. Moreover, multiple antioxidants could mitigate these bystander effects, though at different efficacies in vitro and in vivo. Taken together, these findings suggest that RIBE impair human HSCs and HPCs by oxidative DNA damage. This study provides definitive evidence for RIBE on transplanted human HSCs and further justifies the necessity of conducting clinical trials to evaluate different antioxidants to improve the efficacy of HSC transplantation for the patients with hematological or nonhematological disorders.

Due to the environment-friendly properties of palm fiber, its use was attempted to improve the quality of soil together with lime. Unconfined compressive tests were carried out on soils mixed with palm fiber and lime under the three curing conditions of immersion in water, cyclic wetting–drying and air-curing for a series of contents of additives. The static stiffness of five types of samples (the number 1 type is the control sample) was also analyzed against curing conditions, curing time and sample type. Results from the tests show that the immersion in water condition is the best for the formation of unconfined compressive strength (UCS) and static stiffness, while the air-curing condition is the worst. The highest UCS can be acquired with 1% palm fiber and 20.7% lime, and the highest static stiffness was acquired with purely 20.7% lime content. The fastest increase rate is presented by the curing condition of immersion in water. The logarithmic function is more suitable for expressing the relationship between static stiffness and curing time. It is important for site engineers to understand the curing conditions and stabilizing mechanism of palm fiber and lime for the design and construction of civil engineering projects.

Owing to high power and accuracy and low false positive rate in our multi-locus approaches for genome-wide association studies and linkage analyses, these approaches have attracted considerable attention in plant and animal genetics. In large mapping population, however, fast multi-locus random-SNP-effect efficient mixed model association (FASTmrEMMA) and genome-wide composite interval mapping (GCIM) run a relatively long time. To address this issue, we proposed the improved FASTmrEMMA and GCIM algorithms in this study. In the new algorithms, some matrix identities, such as the Woodbury matrix identity, were used. In scanning each marker on the entire genome, in other words, the improved algorithms effectively replace the expensive eigenvector solutions in (restricted) maximum likelihood estimations in original algorithms with two (one) updated inner products and one updated vector-matrix-vector multiplication. Simulated and real data analyses showed that their computational efficiencies are increased sharply in large mapping population, although there are no mapping result differences between original and improved algorithms. In addition, the related software packages (mrMLM.GUI and QTL.gCIMapping.GUI) can be downloaded from the R and BioCode websites.

In recent years, rare earth metal-organic frameworks (RE-MOFs) have attracted increasing attention because of abundant coordination behaviors, adjustable channels and stable networks. The various electron structures of rare earth ions contribute to the catalytic applications of RE-MOFs and their derivates. In this review, we systematically summarize the research progress that using RE-MOFs and their derivates as catalysts for organic reaction, photocatalytic reaction, and CO oxidation reaction. The major parts include synthetic strategies and catalytic applications of the RE-MOFs. Finally, impressive achievements of RE-MOF catalysts are emerging and a prospect is provided for the development of RE-MOF catalysts at the end of the review.

The bone marrow (BM) niche regulates multiple hematopoietic stem cell (HSC) processes. Clinical treatment for hematological malignancies by HSC transplantation often requires preconditioning via total body irradiation, which severely and irreversibly impairs the BM niche and HSC regeneration. Novel strategies are needed to enhance HSC regeneration in irradiated BM. We compared the effects of EGF, FGF2, and PDGFB on HSC regeneration using human mesenchymal stem cells (MSCs) that were transduced with these factors via lentiviral vectors. Among the above niche factors tested, MSCs transduced with PDGFB (PDGFB-MSCs) most significantly improved human HSC engraftment in immunodeficient mice. PDGFB-MSC-treated BM enhanced transplanted human HSC self-renewal in secondary transplantations more efficiently than GFP-transduced MSCs (GFP-MSCs). Gene set enrichment analysis showed increased antiapoptotic signaling in PDGFB-MSCs compared with GFP-MSCs. PDGFB-MSCs exhibited enhanced survival and expansion after transplantation, resulting in an enlarged humanized niche cell pool that provide a better humanized microenvironment to facilitate superior engraftment and proliferation of human hematopoietic cells. Our studies demonstrate the efficacy of PDGFB-MSCs in supporting human HSC engraftment.

Rh(III)-catalyzed coupling between acrylic acids and yndienones has been realized for the synthesis of cis-hydrobenzofuranone. The reaction proceeded in excellent regio- and stereoselectivity under mild and redox-neutral conditions via a sequence of carboxylic acid-directed olefinic C–H activation, alkyne insertion, and Michael addition. Representative products were found to exhibit cytotoxicity toward the A549 cancer cell line at micromolar levels.

Sensitive and quantitative detection of chemical and biological molecules for screening, diagnosis and monitoring diseases is essential to treatment planning and response monitoring. Electrochemical biosensors are fast, sensitive, and easy to miniaturize, which has led to rapid development in clinical diagnosis. Benefiting from their excellent molecular recognition ability and high programmability, DNA nanomaterials could overcome the Debye length of electrochemical biosensors by simple molecular design and are well suited as recognition elements for electrochemical biosensors. Therefore, to enhance the sensitivity and specificity of electrochemical biosensors, significant progress has been made in recent years by optimizing the DNA nanomaterials design. Here, the establishment of electrochemical sensing strategies based on DNA nanomaterials is reviewed in detail. First, the structural design of DNA nanomaterial is examined to enhance the sensitivity of electrochemical biosensors by improving recognition and overcoming Debye length. In addition, the strategies of electrical signal transduction and signal amplification based on DNA nanomaterials are reviewed, and the applications of DNA nanomaterial-based electrochemical biosensors and integrated devices in clinical diagnosis are further summarized. Finally, the main opportunities and challenges of DNA nanomaterial-based electrochemical biosensors in detecting disease biomarkers are presented in an aim to guide the design of DNA nanomaterial-based electrochemical devices with high sensitivity and specificity.

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a promising therapeutic target in inflammation-related diseases. However, the inhibition of IRAK4 kinase activity may lead to moderate anti-inflammatory efficacy owing to the dual role of IRAK4 as an active kinase and a scaffolding protein. Herein, we report the design, synthesis, and biological evaluation of an efficient and selective IRAK4 proteolysis-targeting chimeric molecule that eliminates IRAK4 scaffolding functions. The most potent compound, LC-MI-3, effectively degraded cellular IRAK4, with a half-maximal degradation concentration of 47.3 nM. LC-MI-3 effectively inhibited the activation of downstream nuclear factor-κB signaling and exerted more potent pharmacological effects than traditional kinase inhibitors. Furthermore, LC-MI-3 exerted significant therapeutic effects in lipopolysaccharide- and Escherichia coli-induced acute and chronic inflammatory skin models compared with kinase inhibitors in vivo. Therefore, LC-MI-3 is a candidate IRAK4 degrader in alternative targeting strategies and advanced drug development.

Therapeutic angiogenesis has become a promising approach for treating ischemic heart disease (IHD). The present study aims to investigate the effects of Qishen Granule (QSG) on angiogenesis in myocardial ischemia (MI) and the potential mechanism.

A kind of drug-loaded nanomotors with deep penetration was developed to improve the therapeutic effect of ferroptosis on tumor. The nanomotors were constructed by co-loading hemin and ferrocene (Fc) on the surface of bowl-shaped polydopamine (PDA) nanoparticles. The near-infrared response of PDA makes the nanomotor have high tumor penetration capability. In vitroexperiments show that the nanomotors can exhibit good biocompatibility, high light to heat conversion efficiency, and deep tumor permeability. It is worth noting that under the catalysis of H2O2overexpressed in the tumor microenvironment, the Fenton-like reagents hemin and Fc loaded on the nanomotors can increase the concentration of toxic •OH. Furthermore, hemin can consume glutathione in tumor cells and trigger the up-regulation of heme oxygenase-1, which can efficiently decompose hemin to Fe2+, thus producing the Fenton reaction and causing a ferroptosis effect. Notably, thanks to the photothermal effect of PDA, it can enhance the generation of reactive oxygen species and thus intervene in the Fenton reaction process, thereby enhancing the ferroptosis effect photothermally. In vivoantitumor results show that the drug-loaded nanomotors with high penetrability showed an effective antitumor therapeutic effect.

Avian leukemia virus subgroup J (ALV-J) and chicken infectious anemia virus (CIAV) can be vertically transmitted; however, the pathogenicity of vertically transmitted coinfection with these 2 pathogens has not been studied. In this study, we created a model of chick morbidity in which chicks carried either ALV-J, CIAV, or both viruses via embryo inoculation. Thereafter, we analyzed the effects of vertically transmitted coinfection with CIAV and ALV-J on the pathogenicity of ALV-J and performed a purification assay based on hatching, mortality viremia positivity, and detection of fecal ALV-p27 antigen rates, and body weight. The hatching rate of the ALV-J+CIAV group was 68.57%, lower than those of the single infection and control groups. The survival curve showed that the mortality rates of the CIAV and ALV-J coinfection groups were higher than those of the single infection and control groups. Body weight statistics showed that coinfection aggravated the 7-d growth inhibition effect. The results of ALV-p27 antigen detection in cell culture supernatants showed that the positivity rates of the ALV-J and ALV-J+CIAV groups were 100% at all ages and 0% in the control group. The results of ALV-p27 antigen detection by anal swabs showed that the positivity rates of the ALV-J group were 92.86, 90.90, 88.89, and 93.33% at all ages, and that the ALV-J p27 positivity detection rate of anal swabs was lower than that of plasma virus isolation. The immune organ index of the ALV-J+CIAV group was significantly or very significantly lower than those of the single infection and control groups. The immune organ viral load showed that coinfection with CIAV and ALV-J promoted the proliferation of ALV-J and CIAV in immune organs. Coinfection with ALV-J and CIAV reduced chicken embryo hatchability and increased chick mortality and growth inhibition relative to their respective single infections. Additionally, coinfection with ALV-J + CIAV was even more detrimental in inducing immune organ atrophy (e.g., the thymus, spleen, and bursa), and promoted individual virus replication during coinfection.

Islet autoantibodies occur in type 2 diabetes. Our study aimed to investigate the prevalence of positive islet autoimmunity in community patients with type 2 diabetes.A total of 495 community patients with type 2 diabetes were recruited using the method of cluster sampling in this cross-sectional study. Three islet autoantibodies including glutamic acid decarboxylase antibody (GADA), insulin autoantibody (IAA) and islet cell antibody (ICA) were measured, and clinical characteristics involved in those individuals were evaluated.The positive rate of islet autoantibodies was 28.5% in total, while combinations of different autoantibodies were rarely seen. Compared with GADA-negative group, positive counterparts significantly tended to have lower levels of body mass index (BMI), waist-hip ratio (WHR), and urinary microalbumin (mALB) (P< 0.05). Adjusted for confounding factors, WHR, triglycerides (TG), and mALB seemed to be negative independent predictors of GADA (OR < 1, P< 0.05). Patients with positive IAA tended to receive insulin treatment (P< 0.0001). Besides, fasting blood glucose (FBG), serum levels of high-density lipoprotein cholesterol (HDL-CH), aspartate transaminase (AST), and γ-glutamyltransferase (GGT) were more likely to be higher in IAA positive subgroup in comparison with the negative counterparts. While after AST was adjusted by unconditional logistic regression analysis, history of insulin treatment, FBG, HDL-CH, and GGT were confirmed as positive predictors of IAA. Furthermore, in patients who were IAA positive, those treated with exogenous insulin tended to have longer duration of diabetes than non-insulin treatment counterparts (P< 0.0001). With regard to ICA, however, there were no significant differences between the two subgroups, except that serum level of AST/ALT seemed to be slightly different (P= 0.064).These data suggested that type 2 diabetic community patients with positive GADA tended to be lean and were able to maintain normal lipid metabolism, while patients with positivity of IAA were frequently accompanied with insulin treatment and more closely associated with diabetic liver damage.

Wearable electronic devices have attracted numerous attention in tactile sensing, motion detecting, and biomedical signal monitoring. In particular, a wearable and self-powered sensor combining all the merits of sensitivity, transparency, stretchability, and flexibility is highly demanded to adapt human skins. Herein, we report a fully transparent, highly stretchable, and self-powered contact-separation triboelectric nanogenerator (TENG) as a tactile sensor. The TENG consists of a double-network ionogel with the transparency, stretchability, and conductivity as the electrode and one friction layer, and patterned polydimethylsiloxane (PDMS) as another friction layer. The fabricated sensor reaches a maximum sensitivity of 1.76 V N−1when detecting impacting forces in the range of 0.1–1 N. Meanwhile, with good stretchability of the sensor, the triboelectric signals maintain a good linearity with impacting forces at different tensile ratios (0%, 10%, 50%, and 80% strain). These properties enable the sensor to be capable of monitoring a variety of human activities, including finger touching and bending, breathing, and pulse beating. We believe such a transparent, stretchable and self-powered tactile TENG sensor has tremendous application potential in wearable and soft electronics.

Typical nanocomposite heterogeneous ZnSb-Al2O3and ZnSb-ZnO phase-change materials were prepared. A direct comparison of the distinct structures in the amorphous, metastable, and stable states between two different materials was investigated systematically. Upon heating, ZnSb-Al2O3films show a two-step crystallization process with the formation of the metastable orthorhombic ZnSb phase ahead of the stable trigonal ZnSb phase, while ZnSb-ZnO films could exhibit a one-step crystallization process with the formation of the stable trigonal ZnSb phase when the ZnO-doping concentration is more than 12.3 atom %. In the case of ZnSb-Al2O3, the structural transition to the metastable phase is accompanied by a pronounced increase in the grain size up to 100 nm. Such an increase in the crystal grain size is not found in ZnSb-ZnO films; i.e., the nanocrystals do not grow significantly when the crystallized film is precipitated with the metastable ZnSb phase. By the method of advanced scanning transmission electron microscopy, we clearly find that the grain growth is limited by the separated ZnO domain formation, which improves the amorphous thermal stability significantly with the optimized 10-year data retention ability up to 229.2 °C for (ZnSb)81.8(ZnO)18.2film.

Low-molecular-weight (low-MW) compounds have many essential functions in biological processes, and the molecular imaging of as many low-MW compounds as possible is critical for understanding complex biological processes. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is an emerging molecular-imaging technology that enables determination of the spatial distributions and the relative abundances of diverse endogenous compounds in tissues. New matrices suitable for the imaging of low-MW compounds by MALDI-MSI are important for the technological advancement of tissue imaging. In this study, 3,4-dimethoxycinnamic acid (DMCA) was evaluated as a new matrix for enhanced low-MW compound detection by MALDI-MSI because of its strong ultraviolet absorption, low matrix-ion related interferences below m/z500, and high ionization efficiency for the analysis of low-MW compounds. DMCA was successfully used for improved in situ detection of low-molecular-weight metabolites (m/z< 500) and lipids in rat liver, rat brain, and germinating Chinese-yew seed tissue sections. The use of DMCA led to the successful in situ detection of 303, 200, and 248 low-MW compound ion signals from these three tissues, respectively. Both MALDI-MS/MS and LC-MS/MS were used to identify these ion signals, leading to the identification of 115 low-MW compounds from rat liver (including 53 lipids, 29 oligopeptides, and 33 metabolites), 130 low-MW compounds from rat brain (including 104 lipids, 5 oligopeptides, and 21 metabolites), and 111 low-MW compounds from germinating Chinese-yew seeds (including 77 lipids, 22 oligopeptides, 8 flavonoids, and 4 alkaloids). A larger number of low-MW compounds could be detected and imaged when DMCA was used as the MALDI matrix than with other commonly used MALDI matrices such as 2,5-dihydroxybenzoic acid, α-cyano-4-hydroxycinnamic acid, 2-mercaptobenzothiazole, graphene oxide, and silver nanoparticles. Our work provides a new and powerful matrix for enhanced MALDI-MS profiling of low-MW compounds in both animal and plant tissues.

The coal gasification behaviors in the pressurized high-density circulating fluidized bed under various solids circulation fluxes were studied with the CFD method, which combines the two-fluid model and coal gasification reactions represented by the chemical percolation devolatilization and the MGAS models. The numerical method was validated with two experimental cases, and detailed distributions of gas species and temperature in the riser were illustrated to understand the gasification process. To fully understand the influence of solids circulation flux on the gasification behavior, a series of cases were simulated with the solids flux varying gradually from 260 to 1010 kg/m2s, and the composition and quality of syngas were compared between various cases. The higher heating value of syngas firstly increased and then decreased with the increase of solids flux, and it reached the highest value around 480 kg/m2s. The influence of solids flux on gasification process was further analyzed through the contours of temperature, solids concentration, and gas composition in the riser.

Conventional oral therapy for ulcerative colitis (UC) is associated with premature release or degradation of drugs in the harsh gastrointestinal environment, resulting in reduced therapeutic effectiveness. Consequently, the present study aims to develop a dual‐targeted delivery system with a nanoparticle‐in‐microparticle (nano‐in‐micro) structure. The prepared Asiatic Acid‐loaded delivery system (AA/CDM‐BT‐ALG) has pH‐sensitive properties. Cellular uptake evaluation confirms that nanoparticles exhibit targeted absorption by macrophages and Caco‐2 cells through mannose (Man) receptor and biotin‐mediated endocytosis, respectively. Therefore, this mechanism effectively enhances intracellular drug concentration. Additionally, the biodistribution study conducted on the gastrointestinal tract of mice indicates that the colon of the microspheres group shows higher fluorescence intensity with longer duration than the other groups. This finding indicates that the microspheres exhibit selective accumulation in areas of colon inflammation. In vivo experiments in colitis mice showed that AA/CDM‐BT‐ALG significantly alleviates the histopathological characteristics of the colon, reduced neutrophil, and macrophage infiltration, and decreases pro‐inflammatory cytokine expression. Furthermore, the effect of AA/CDM‐BT‐ALG on colitis is validated to be closely related to the TLR4/MyD88/NF‐κB signaling pathway. The present findings suggest that the development of a dual‐targeted delivery system is accomplished effectively, with the potential to serve as a drug‐controlled release system for treating UC. A dual‐targeted nanoparticle‐in‐microparticle system is designed for the treatment of UC. The therapeutic effect is achieved through three steps: 1) The ALG shell of AA/CDM‐BT‐ALG microspheres dissolves in the intestinal environment and releases nano‐micelles in the colon. 2) Bio‐TPGS micelles transmembrane into cells by targeting SMVT‐mediated endocytosis. 3) CS‐DCA‐Man micelles target macrophages at inflammatory sites and inhibit inflammatory factors.

Characterising and sourcing natural stones are essential for not only understanding the historical information carried by heritage buildings and cultural heritage sites, but also providing necessary data for restoration and conservations. Petrographic analyses by polarised microscopy, along with the integrated chemical data acquired by inductively coupled plasma-mass spectrometry (ICP-MS) and X-ray diffraction (XRD) analysis, allowed us to ascertain the compositions of stone materials. In this paper it is applied on samples collected from quarries of “three famous stones (Meiyuanshi-, Xiaoxishi-, and Dayinshi-stone)” in Ningbo and from the Sumeru platform in the main hall of Baoguosi Temple (Ningbo, Zhejiang, China). Comparison of petrographic features, major and trace elements of the stones studied indicated that they are all tuffs but of different characteristics and origin. Moreover, we were able to confirm that the Sumeru platform in Baoguosi is made of Meiyuanshi-stone. The results have demonstrated the suitability of the approach and present a practicable solution for other stone buildings.

Objective:Thetherapeutic approach for transfusion-dependent non-severe aplastic anemia (TD-NSAA) is undetermined. Though the British guideline recommended intensive immunosuppressive therapy (IST) as front-line therapy for TD-NSAA ( Killick SB, et al. British Journal of Haematology. 2016; 172(2): 187-207), the cost and risk were relatively high. Hetrombopag is a thrombopoietin receptor agonist approved for IST-refractory severe aplastic anemia (SAA) by the China Food and Drug Administration in 2021 ( Peng G, et al. Ther Adv Hematol. 2022; 13: 20406207221085197). This study aimed to evaluate the efficacy of hetrombopag plus cyclosporine A (CsA) for TD-NSAA.

Umbilical cord blood transplantation (UCBT) has been performed broadly in clinic by the specific biological and immunological characteristics of umbilical cord blood cells (UCB). UCB-based cell therapy and immune therapy also presents great application potential. UCB was usually cryopreserved for several years before using. Whether and how cryopreservation affects the function of divergent cell populations in UCB still remain to be illuminated.