Ex Vivo Expansion and Homing of Human Cord Blood Hematopoietic Stem Cells.

Cord blood (CB) has been proven to be an alternative source of haematopoietic stem cells (HSCs) for clinical transplantation and has multiple advantages, including but not limited to greater HLA compatibility, lower incidence of graft-versus-host disease (GvHD), higher survival rates and lower relapse rates among patients with minimal residual disease. However, the limited number of HSCs in a single CB unit limits the wider use of CB in clinical treatment. Many efforts have been made to enhance the efficacy of CB HSC transplantation, particularly by ex vivo expansion or enhancing the homing efficiency of HSCs. In this chapter, we will document the major advances regarding human HSC ex vivo expansion and homing and will also discuss the possibility of clinical translation of such laboratory work.

Long non-coding RNA growth arrest-specific 5 and its targets, microRNA-21 and microRNA-140, are potential biomarkers of allergic rhinitis.

OBJECTIVE: Long non-coding RNA growth arrest-specific 5 (lnc-GAS5) and its targets (microRNA [miR]-21 and miR-140) are involved in the development and progression of allergic rhinitis (AR). However, the correlation of lnc-GAS5 with miR-21 and miR-140 and their associations with disease risk, symptom severity, and Th1/Th2 cytokines in AR remain unclear. Thus, this study aimed to investigate this topic. METHODS: In total, 120 patients with AR and 60 controls were recruited. Nasal-mucosa tissues were collected from all participants. Lnc-GAS5, its targets (miR-21 and miR-140), interferon (IFN)-γ, interleukin (IL)-2, IL-4, and IL-10 were detected by reverse-transcription quantitative polymerase chain reaction. RESULTS: Lnc-GAS5 was elevated, while miR-21 and miR-140 was downregulated in AR patients than in controls (p < 0.001). In AR patients, lnc-GAS5 was negatively correlated with miR-21 (p < 0.001), miR-140 (p < 0.001), IFN-γ (p = 0.019), and IL-2 (p = 0.039) and positively correlated with IL-4 (p = 0.004) and IL-10 (p < 0.001), individual nasal symptom scores (INSSs) for itching, sneezing, and congestion (p < 0.05), and total nasal symptom score (TNSS) (p < 0.001). Moreover, miR-21 and miR-140 were negatively correlated with some INSSs, total TNSS score, and IL-10 and positively correlated with IFN-γ and IL-2 (p < 0.05). CONCLUSION: Lnc-GAS5 is negatively correlated with that of its targets (miR-21 and miR-140) in AR; meanwhile, lnc-GAS5, miR-21, and miR-140 are correlated with disease risk, symptom severity, and Th1/Th2 imbalance in AR, suggesting the potential of these biomarkers in the development and progression of AR.

The Chaperone Protein Cct5 is Essential for Hematopoietic Stem Cell Maintenance.

Proper proteostasis is indispensable for the long-term maintenance of hematopoietic stem and progenitor cells (HSPCs). The TRiC/CCT (chaperonin-containing TCP-1) complex, a key constituent of cellular machinery facilitating accurate protein folding, has remained enigmatic in its specific function within HSPCs. Here we show that conditional knockout (KO) of Cct5 significantly impairs the maintenance of murine HSPCs. Primary and secondary transplantation experiments unequivocally demonstrate the incapacity of Cct5 KO HSPCs to reconstitute both myeloid and lymphoid lineage cells in recipient mice, highlighting the pivotal role of the TRiC/CCT complex in governing these cellular lineages. Furthermore, leveraging an integrated approach that merges a Protein-Protein Interaction (PPI) database with RNA sequencing (RNA-seq) data of HSPCs, our analysis reveals intricate interactions between Cct5 and vital transcription factors crucial for HSC homeostasis. Notably, Cct5 engages with MYC, PIAS1, TP53, ESR1, HOXA1, and JUN, intricately regulating the transcriptional landscape governing autophagy, myeloid differentiation, and cytoskeleton organization within HSPCs. Our study unveils the profound significance of TRiC/CCT complex-mediated proteostasis in orchestrating the maintenance and functionality of HSPCs.

Synthesis of Guanine/Vermiculite Two-Dimensional Nanocomposites for Wireless Humidity Sensing in Nut Storage Environment.

Two-dimensional (2D) nanostructures have the advantages of high specific surface area, easy surface functionalization, abundant active sites, and good compatibility with device integration and can be assembled into three-dimensional structures, which are key to the development of high-performance gas sensors. In this study, 2D vermiculite (VMT) nanosheets and guanine (G), two renewable resources with unique chemical structures, were organically combined to fully use the specificity of their molecular structures and functional activities. Driven by the regulation of 2D VMT nanosheets, guanine/vermiculite (G/VMT)-based 2D nanocomposites with controllable pore structure, multiple binding sites, and unobstructed mass transfer were designed and synthesized. The G/VMT nanocomposite material was used as a quartz crystal microbalance (QCM) electrode-sensitive film material to build a QCM-based humidity sensor. G/VMT-based QCM humidity sensor had good logarithmic linear relation (0.9971), high sensitivity (24.49 Hz/% relative humidity), low hysteresis (1.75% RH), fast response/recovery time (39/6 s), and good stability. Furthermore, with a QCM sensor and a specially designed wireless circuit, a wireless humidity detection system transmitting via Wi-Fi allows real-time monitoring of nut storage. This study presents an environmentally friendly, high-performance, miniature 2D nanocomposite sensor strategy for real-time monitoring.

Aspartyl-tRNA synthetase 2 orchestrates iron-sulfur metabolism in hematopoietic stem cells via fine-tuning alternative RNA splicing.

Aspartyl-tRNA synthetase 2 (Dars2) is involved in the regulation of mitochondrial protein synthesis and tissue-specific mitochondrial unfolded protein response (UPRmt). The role of Dars2 in the self-renewal and differentiation of hematopoietic stem cells (HSCs) is unknown. Here, we show that knockout (KO) of Dars2 significantly impairs the maintenance of hematopoietic stem and progenitor cells (HSPCs) without involving its tRNA synthetase activity. Dars2 KO results in significantly reduced expression of Srsf2/3/6 and impairs multiple events of mRNA alternative splicing (AS). Dars2 directly localizes to Srsf3-labeled spliceosomes in HSPCs and regulates the stability of Srsf3. Dars2-deficient HSPCs exhibit aberrant AS of mTOR and Slc22a17. Dars2 KO greatly suppresses the levels of labile ferrous iron and iron-sulfur cluster-containing proteins, which dampens mitochondrial metabolic activity and DNA damage repair pathways in HSPCs. Our study reveals that Dars2 plays a crucial role in the iron-sulfur metabolism and maintenance of HSPCs by modulating RNA splicing.

[Preparation of Bamboo-based N, P Co-doped Activated Carbon and Its Lanthanum Ion Adsorption Performance].

Using diammonium hydrogen phosphate as an activator and N and P source and and bamboo chips as the carbon source, N, P co-doped activated carbon was prepared by one-step pyrolysis and used to efficiently remove La3+ in aqueous solutions. The effects of activation temperature and pH value on the adsorption performance of La3+ were analyzed, and the activation and adsorption mechanisms were explored using TG-IR, SEM-EDX, pore structure, XPS, and hydrophilicity. The results showed that diammonium hydrogen phosphate easily decomposed at a high temperature to produce ammonia and phosphoric acid, which activated the material and promoted the increase in the specific surface area and pore volume of the activated carbon. As an N and P source, the addition of diammonium hydrogen phosphate successfully achieved the N, P co-doping of activated carbon, and the introduction of N- and P-containing functional groups was the key to enhance the adsorption of La3+. Among them, graphitic nitrogen could provide interactions between La3+-π bonds, and C-P=O and C/P-O-P could provide active sites for the adsorption of La3+ through complexation and electrostatic interaction. The adsorption of La3+ on N, P co-doped activated carbons was endothermic and spontaneous, and the adsorption process conformed to the Langmuir isotherm and secondary kinetic model. Under the process conditions of an activation temperature of 900℃ and pH=6, the adsorption capacity of the N, P co-doped activated carbon was as high as 55.18 mg·g-1, which was 2.53 times higher than that of the undoped sample, and its adsorption selectivity for La3+ in the La3+/Na+and La3+/Ca2+ coexistence systems reached 93.49% and 82.49%, respectively. Additionally, the removal efficiency remained above 54% after five successive adsorption-desorption cycle experiments.

Dihydroxybenzene isomers electrochemical sensor based on activated carbon sensitive material activated by mechanochemistry and low-dosage phosphoric acid.

A dihydroxybenzene isomers electrochemical sensor based on bamboo activated carbon (MCPBAC) sensitive material activated by mechanochemistry and low-dosage phosphoric acid was fabricated in this work. The sensor, modified by MCPBAC with GCE, can significantly distinguish and sensitively measure hydroquinone (HQ) and catechol (CC). The MCPBAC exhibits a well-developed porous structure, high specific surface area, and good electrical conductivity. Using differential pulse voltammetry (DPV), wide linear ranges for both HQ and CC are 0.6-600 µM, with low detection limits (S/N = 3) for both of 0.2 µM. The dihydroxybenzene isomers electrochemical sensor has wide application prospects in the determination of trace HQ and CC in environmental water.

ADGRG1 enriches for functional human hematopoietic stem cells following ex vivo expansion-induced mitochondrial oxidative stress.

The heterogeneity of human hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) under stress conditions such as ex vivo expansion is poorly understood. Here, we report that the frequencies of SCID-repopulating cells were greatly decreased in cord blood (CB) CD34+ HSCs and HPCs upon ex vivo culturing. Transcriptomic analysis and metabolic profiling demonstrated that mitochondrial oxidative stress of human CB HSCs and HPCs notably increased, along with loss of stemness. Limiting dilution analysis revealed that functional human HSCs were enriched in cell populations with low levels of mitochondrial ROS (mitoROS) during ex vivo culturing. Using single-cell RNA-Seq analysis of the mitoROS low cell population, we demonstrated that functional HSCs were substantially enriched in the adhesion GPCR G1-positive (ADGRG1+) population of CD34+CD133+ CB cells upon ex vivo expansion stress. Gene set enrichment analysis revealed that HSC signature genes including MSI2 and MLLT3 were enriched in CD34+CD133+ADGRG1+ CB HSCs. Our study reveals that ADGRG1 enriches for functional human HSCs under oxidative stress during ex vivo culturing, which can be a reliable target for drug screening of agonists of HSC expansion.

A bioinspired hydrogen bond crosslink strategy toward toughening ultrastrong and multifunctional nanocomposite hydrogels.

Developing physical hydrogels with advanced mechanical performance and multi-functionalities as alterative materials for load-bearing soft tissues remains a great challenge. Biological protein-based materials generally exhibit superior strength and toughness owing to their hierarchical structures via hydrogen-bonding assembly. Inspired by natural biological protein materials, tannic acid (TA) is exploited as a molecular coupling bridge between cellulose nanocrystals (CNCs) and poly(vinyl alcohol) (PVA) chains for the fabrication of a bio-based advanced physical hydrogel via strong multiple H-bonds. When exposed to mechanical stress, the sacrificial H-bonds can dissipate energy effectively on the molecular scale via dynamic rupture and reformation, endowing these biomimetic hydrogels with remarkable toughness, ultrahigh strength, large elongation, and good self-recoverability, which are much superior to those of most hydrogen bond-based hydrogels. Moreover, the characteristics of TA endow these biomimetic hydrogels with versatile adhesiveness and good antibacterial properties. This work presents an innovative biomimetic strategy for robust biocompatible hydrogels with superior mechanical strength and functionalities, which holds great promise for applications in tissue engineering and biomedical fields.

On preparing highly abrasion resistant binderless and in situ N-doped granular activated carbon.

NaOH/urea, a cellulose solvent, has been applied for the preparation of binderless and in situ N-doped GACs (NaOH/urea-GACs). The dissolved cellulose binds lignin, hemicellulose and undissolved cellulose all together to form a granular precursor after kneading and extruding. During the process, NaOH and urea are dispersed in sawdust where the NaOH acts as an activator at high temperatures, and the urea plays the role of an in situ N-dopant. The results show that at a mass concentration ratio of 14 wt% NaOH/24 wt% urea which has been activated for 1 h at 850 °C after kneading for 2 h GACs with a specific surface area (S BET) of 811.299 m2 g-1, a microporosity of 59.20% and an abrasion resistance of 99.83% are obtained. The N content as well as its form of existence are also further explored. The desulfurization ability of the NaOH/urea-GACs is also investigated, and NaOH/urea-GACs, without removed alkali, are applied for desulfurization, and the adsorption process is appropriate for the Bangham model. The experimental results indicate that it is feasible to use an NaOH/urea solvent as a suitable chemical for the manufacture of GACs with good properties.

One-pot construction of cellulose-gelatin supramolecular hydrogels with high strength and pH-responsive properties.

Inspired by the supramolecular structure of cellulose, cellulose-gelatin supramolecular hydrogels with high strength and pH-sensitivity were constructed in a basic-based solvent system, ethylene diamine/potassium thiocyanate (EDA/KSCN) with the aid of cyclic freezing-thawing. The investigation on the characteristics of supramolecular hydrogels revealed that repeated freezing-thawing cycles played an important role in the formation of the physical cross-linked supramolecular network structure between cellulose and gelatin. The mechanical properties of supramolecular hydrogels were much higher than pure cellulose and gelatin hydrogel, and the compressive strength was 9.6 times higher than that of pure gelatin hydrogel. The synergistic effect between hydrogen-bonding interaction and the reinforcement of regenerated cellulose nanofibrils (CNF) contributed to the superior mechanical performance. Furthermore, the swelling kinetics tests showed that the supramolecular hydrogels exhibited excellent pH-responsibility, indicating potential applications in biomedical fields. Thus, a straightforward route to construct natural polymer-based hydrogels with supramolecular structure through physical crosslinking strategy without employing hazardous crosslinking agents was developed, paving the way for the design of new types of hydrogels.

Effect of silicone oil heat treatment on the chemical composition, cellulose crystalline structure and contact angle of Chinese parasol wood.

The effect of silicone oil heat treatment (SOTH) on the chemical composition, cellulose crystalline structure, thermal degradation and contact angle of Chinese parasol wood were examined in this study. Samples were heated at 150°C, 180°C and 210°C for 2h and 8h, after SOHT chemical composition, fourier transformed infrared (FTIR), thermogravimetric analysis (TGA) and X-ray diffraction (XRD) of the treated samples were evaluated. Results showed that the chemical components of the wood were affected after SOHT particularly when treated at 210°C for 8h. Changes in the chemical components was due to the degradation of biopolymer components of the wood during SOHT. The crystallinity index of cellulose and contact angle of the SOHT samples was increased. The findings demonstrate the potential of SOHT for modification of wood. Thus an economical and eco-friendly approach to thermally modified wood was achieved in this study.

Dexmedetomidine attenuates hypoxemia during palliative reconstruction of the right ventricular outflow tract in pediatric patients.

The objective of this study was to investigate whether the α agonist dexmedetomidine has the ability to attenuate hypoxemia in pediatric patients undergoing palliative pulmonary artery reconstruction.From January 2009 to January 2013, a total of 25 pediatric patients with Tetralogy of Fallot, pulmonary atresia (ventricular septal defect), or persistent truncus arteriosus (I) were enrolled in our study. Due to hypoplastic pulmonary arteries, all patients received palliative pulmonary artery reconstruction. During the perioperative period, they were allocated to receive either dexmedetomidine (bolus dose of 0.3 µg/kg followed by an infusion of 0.2-0.3 µg/kg/h, n = 15) or control drug (n = 10) intravenously. Any desaturation was recorded. Heart rate, mean arterial pressure, pulse oximetry, and arterial blood gas parameters were measured during the perioperative period.There were no significant differences between the groups in hemodynamic variables. The arterial oxygen saturation and arterial blood gas parameters increased in the dexmedetomidine groups (P < 0.05).These findings suggest that the injection of dexmedetomidine can attenuate hypoxemia during palliative pulmonary artery reconstruction in pediatric patients.

No association of functional variant in pri-miR-218 and risk of congenital heart disease in a Chinese population.

BACKGROUND: MiR-218 plays an important role in heart development in zebrafish. pri-miR-218 rs11134527 variant is associated with cervical cancer carcinogenesis. Therefore, we hypothesized that single nucleotide polymorphism (SNPs) in pri-miR-218 might influence susceptibility to sporadic congenital heart disease (CHD). METHODS AND RESULTS: We conducted a case-control study of CHD in a Chinese population to test our hypothesis by sequencing and genotyping pri-miR-218 in 1116 CHD cases and 1219 non-CHD controls. We identified one SNP rs11134527 located in pri-miR-218 sequence. Logistic regression analyses showed that there was no significant association in genotype and allele frequencies of pri-miR-218 rs11134527 A/G polymorphism between CHD cases in overall or various subtypes and the control group. However, real-time PCR analysis showed that rs11134527 allele G significantly increased mature miR-218 expression. In vitro binding assays further revealed that the rs11134527 variant affects miR-218-mediated regulation of Robo1. CONCLUSIONS: This is the first study to investigate the relationship between miR-218 and CHD cases. Our results demonstrate that the functional variant rs11134527 in pri-miR-218 has no major role in genetic susceptibility to sporadic CHD, at least in the population studied here.

Manufacture of cellulose nanocrystals by cation exchange resin-catalyzed hydrolysis of cellulose.

Cellulose nanocrystals (CNC) were prepared from microcrystalline cellulose (MCC) by hydrolysis with cation exchange resin (NKC-9) or 64% sulfuric acid. The cation exchange resin hydrolysis parameters were optimized by using the Box-Behnken design and response surface methodology. An optimum yield (50.04%) was achieved at a ratio of resin to MCC (w/w) of 10, a temperature of 48 °C and a reaction time of 189 min. Electron microscopy (EM) showed that the diameter of CNCs was about 10-40 nm, and the length was 100-400 nm. Regular short rod-like CNCs were obtained by sulfuric acid hydrolysis, while long and thin crystals of cellulose were obtained with the cation exchange resin. X-ray diffraction (XRD) showed that, compared with MCC, the crystallinity of H2SO4-CNC and resin-CNC increased from 72.25% to 77.29% and 84.26%, respectively. The research shows that cation exchange resin-catalyzed hydrolysis of cellulose could be an excellent method for manufacturing of CNC in an environmental-friendly way.

Heterovalent Au(III)-M(I) (M=Cu, Ag, Au) complexes derived from incorporation of [Au(tdt)2]- (tdt = toluene-3,4-dithiolate) with [M2(dppm)2]2+ (dppm = Bis(diphenylphosphino)methane).

Polynuclear heterovalent Au(III)-M(I) (M = Cu, Ag, Au) cluster complexes [Au(III)Cu(I)8(mu-dppm)3(tdt)5]+ (1), [Au(III)3Ag(I)8(mu-dppm)4(tdt)8]+ (2), and [Au(III)Au(I)4(mu-dppm)4(tdt)2]3+ (3) were prepared by reaction of [Au(III)(tdt)2]- (tdt = toluene-3,4-dithiolate) with 2 equiv of [M(I)2(dppm)2]2+ (dppm = bis(diphenylphosphino)methane). Complex 3 originates from incorporation of one [Au(III)(tdt)2]- with two [Au(I)2(dppm)2]2+ components through Au(III)-S-Au(I) linkages. Formation of complexes 1 and 2, however, involves rupture of metal-ligand bonds in the metal components and recombination between the ligands and the metal atoms. The Au(tdt)2 component connects to four M(I) atoms through Au(III)-S-M(I) linkages in syn and anti conformations in complexes 1 (M = Cu) and 3 (M = Au), respectively, but in both syn and anti conformations in complex 2 (M = Ag). The tdt ligand exhibits five types of bonding modes in complexes 1-3, chelating Au(III) or M(I) atoms as well as bridging Au(III)-M(I) or M(I)-M(I) atoms in different orientations. Although complexes 1 and 2 are nonemissive, Au(III)Au(I)(4) complex 3 shows room-temperature luminescence with emission maximum at 555 nm (tau(em) = 3.1 micros) in the solid state and at 570 nm (tau(em) = 1.5 micros) in acetonitrile solution.

Syntheses, characterization, and luminescence of Pt II-M I (M = Cu, Ag, Au) heterometallic complexes by incorporating Pt(diimine)(dithiolate) with [M2(dppm)2]2+ (dppm = Bis(diphenylphosphino)methane).

Reaction of Pt(diimine)(edt) (edt = 1,2-ethanedithiolate) with M(2)(dppm)(2)(MeCN)(2)(2+) (dppm = bis(diphenylphosphino)methane) gave heterotrinuclear complexes [PtCu(2)(edt)(mu-SH)(dppm)(3)](ClO(4)) (11) and [PtCu(2)(diimine)(2)(edt)(dppm)(2)](ClO(4))(2) (diimine = 2,2'-bpyridine (bpy), 12; 4,4'-dibutyl-2,2'-bipyridine (dbbpy), 13; phenanthroline (phen), 14; 5-bromophenanthroline (brphen), 15) when M = Cu(I). The reaction, however, afforded tetra- and trinuclear complexes [Pt(2)Ag(2)(edt)(2)(dppm)(2)](SbF(6))(2) (17) and [PtAu(2)(edt)(dppm)(2)](SbF(6))(2) (21) when M = Ag(I) and Au(I), respectively. The complexes were characterized by elemental analyses, electrospray mass spectroscopy, (1)H and (31)P NMR, IR, and UV-vis spectrometry, and X-ray crystallography for 14, 17, and 18. The Pt(II)Cu(I)(2) heterotrinuclear complexes 11-15 exhibit photoluminescence in the solid states at 298 K and in the frozen acetonitrile glasses at 77 K. It is likely that the emission originates from a ligand-to-metal charge transfer (dithiolate-to-Pt) (3)[p(S) --> d(Pt)] transition for 11 and from an admixture of (3)[d(Cu)/p(S)-pi(diimine)] transitions for 12-16. The Pt(II)(2)Ag(I)(2) heterotetranuclear complexes 17 and 18 are nonemissive in the solid states and in solutions at 298 K but show photoluminescence at 77 K. The Pt(II)Au(I)(2) heterotrinuclear complexes 19-21, however, are luminescent at room temperature in the solid state and in solution. Compounds 19 and 20 afford negative solvatochromism associated with a charge transfer from an orbital of a mixed metal/dithiolate character to a diimine pi orbital.