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Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion.

Adipose derived stem cells (ADSCs) can differentiate into vascular lineages and participate in vascular remodeling. Perivascular ADSCs (PV-ADSCs) draw attention due to their unique location. The heterogeneity of subcutaneous (SUB-) and abdominal ADSCs were well addressed, but PV-ADSCs' heterogeneity hasn't been investigated. In the present study, we applied single-cell analysis to compare SUB-ADSCs and PV-ADSCs respectively regarding their subpopulations, functions, and cell fates. We uncovered 4 subpopulations of PV-ADSCs including Dpp4+, Col4a2+/Icam1+, Clec11a+/Cpe+ and Sult1e1+ cells, among which Clec11a+ subpopulation potentially participated in and regulated the PV-ADSCs differentiation towards a smooth muscle cell (SMC) phenotype. The present study revealed the distinct characteristics between PV-ADSCs and SUB-ADSCs.

Wine-processed Angelica Sinensis is a widely used Chinese medicinal decoction piece in China. However, there are hardly any robust markers indicating the processing procedure of wine-processed Angelica Sinensis, including the amount of rice wine and processing degree. A strategy integrating untargeted metabolomics and chemometric analysis for deducing robust markers was provided and applied to the discrimination of processing procedure. First, 86 compounds were tentatively identified in wine-processed Angelica Sinensis by ultra-high-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry. Second, 93 potential chemical markers were selected using multivariate analysis, among which nine robust chemical markers were selected by verification with commercial samples. Finally, the effects of processing temperature, time, and amount of rice wine on the three selected chemical markers were investigated through a rapid analytical method. It was demonstrated that both m/z 258.1097 and m/z 238.1189 were positively correlated with the amount of rice wine and processing degree. In summary, this study introduced two candidate processing markers as robust markers for discriminating the processing procedures of wine-processed Angelica sinensis. It also proposed a strategy to provide the reference for the research of other decoction pieces. This article is protected by copyright. All rights reserved.

Despite the immense genetic heterogeneity of B-lymphoblastic leukemia [or precursor B-cell acute lymphoblastic leukemia (B-ALL)], RNA sequencing (RNA-Seq) could comprehensively interrogate its genetic drivers, assigning a specific molecular subtype in >90% of patients. However, study groups have only started to use RNA-Seq. For broader clinical use, technical, quality control, and appropriate performance validation are needed. We describe the development and validation of an RNA-Seq workflow for subtype classification, TPMT/NUDT15/TP53 variant discovery, and immunoglobulin heavy chain (IGH) disease clone identification for Malaysia-Singapore acute lymphoblastic leukemia (ALL) 2020. We validated this workflow in 377 patients in our preceding Malaysia-Singapore ALL 2003/Malaysia-Singapore ALL 2010 studies and proposed the quality control measures for RNA quality, library size, sequencing, and data analysis using the International Organization for Standardization 15189 quality and competence standard for medical laboratories. Compared with conventional methods, we achieved >95% accuracy in oncogene fusion identification, digital karyotyping, and TPMT and NUDT15 variant discovery. We found seven pathogenic TP53 mutations, confirmed with Sanger sequencing, which conferred a poorer outcome. Applying this workflow prospectively to the first 21 patients in Malaysia-Singapore ALL 2020, we identified the genetic drivers and IGH disease clones in >90% of patients with concordant TPMT, NUDT15, and TP53 variants using PCR-based methods. The median turnaround time was 12 days, which was clinically actionable. In conclusion, RNA-Seq workflow could be used clinically in management of B-cell ALL patients.

The survival of foodborne pathogens under stressful food processing conditions and in host’s gastrointestinal tract has been widely reported to cause the outbreak of human diseases. Generally, antibiotics have been used to elimi-nate the microbial flora of foodborne pathogens. However, the overuse of antibiotics has contributed to the emergence and spread of multi-drug-resistant foodborne pathogens. Kombucha is a beverage prepared by fermenting sugared tea or other substrates with a symbiotic culture of yeasts and bacteria, and has been proved to fight food-borne pathogens and affect gastrointestinal microbial flora to prevent foodborne illnesses. In this context, this review primarily focused on microbiological and chemical compositions of kombucha obtained by fermenting different substrates. It further discussed the antimicrobial activity of kombucha, as well as potential antimicrobial agents found in kombucha, and the limitations of kombucha in the food industry. In addition, the need for developing antimicrobial agents from kombucha has been discussed for potential applications. The information provided in this review indicates that kombucha could serve as an alternative approach to control pathogens in place of using antibiotics.

Titanium (Ti) is a widely used metallic biomaterial in developing orthopedic implants or devices, but it is often encountered with a poor osteogenic response. In this study, the authors report the surface modification of Ti with cobalt (Co)-containing titanium dioxide (TiO2) coatings by plasma oxidation technique in order to enhance its cellular response. The results were compared between unmodified and surface modified Ti. The scanning electron microscopy (SEM) analysis showed that the surface coating was homogenous and porous throughout the test specimen. Indeed, the energy-dispersive X-ray spectrometry (EDS) analysis showed that the cobalt was evenly distributed on the Ti surface. It was also observed from the preliminary cell culture studies that the surfacemodified Ti has excellent cell compatibility and has promoted the adhesion and proliferation of osteoblasts when compared to the unmodified Ti. The present study clearly demonstrated that the Co-containing plasma electrolytic oxidation is an efficient technique for the surface modification of Ti in order to promote its osteogenic response.

The presence of sulfate groups in agar compromises the agar quality by affecting the crosslinking during gelling process. Some arylsulfatases can catalyze the hydrolysis of sulfate bonds in agar to improve the agar quality. Immobilized arylsulfatases prove beneficial advantages for their industrial applications. Here, a previously characterized mutant arylsulfatase K253H/H260L was immobilized on the synthesized magnetic Fe3O4 nanoparticles after functionalization by tannic acid (MNPs@TA). The surface properties and molecular structures of the immobilized arylsulfatase (MNPs@TA@ARS) were examined by scanning electron microscopy and Fourier transform infrared spectroscopy. Enzymatic characterization showed that MNPs@TA@ARS exhibited shifted optimal temperature and pH with deviated apparent Km and Vmax compared to its free counterpart. The immobilized arylsulfatase demonstrated improved thermal and pH stability and enhanced storage stability with modest reusability. In addition, MNPs@TA@ARS displayed enhanced tolerance to various inhibitors and detergents. The utilization of the immobilized arylsulfatase for agar desulfation brought the treated agar with improved quality.

In the paper, a new one-dimensional (1-D) compound Sine chaotic system (CSCS) is first proposed. Then new chaotic maps are generated by the CSCS. And four novel generated maps are used for the illustration about the CSCS. Secondly, the results of performance analysis show that the four maps have large Lyapunov exponents and high complexity. Thirdly, a high-efficiency image encryption scheme is proposed by employing two of the four new produced chaotic maps. In the proposed encryption scheme, the simplest diffusion operation is used. And we use a variety of scrambling operations, such as Zigzag transform, Magic confusion and the row confusion. In addition, to increase key space and in order to improve the ability to resist two kinds of attacks, namely the known plaintext attack and the selected plaintext attack, the control parameters and the initial values of the two new chaotic systems are generated based on the SHA-256 function. Finally, compared to other schemes, simulation tests show that our scheme not only has higher security but also faster encryption speed.

Through analysis of ABO blood group gene typing technology, to assist in the identification of difficult clinical serological specimens.A total of 10 forwardreverse typing ambiguous samples were collected from January 2021 to August 2021 in our hospital.ABO genotypes were analysed by gene sequencing.The genotypes of 10 ABO ambiguous blood group samples were A102/BW11, A102/BW12, O02/O02, A102/B303, A102/B101, BW11/O02, B101/O04, BW11/O01, BW11/O01, A101/O02, respectively. The genotype results of 6 cases was consistent with the serological phenotype, and the serological phenotype of 4 cases were different from the geno sequencing.ABO blood groups genotyping technology combined with serological typing can be used for accurate typing of ambiguous blood group, and better ensure the safety of blood transfusion.10例ABO疑难血型的基因测序分析.利用ABO血型基因分型技术协助临床血清学疑难血型的鉴定.收集2021年1月－2021年8月本院用血清学鉴定ABO正反定型不符的疑难血型标本10例，采用基因测序方法检测ABO基因型.10例疑难血型标本的ABO基因型分别为A102/Bw11、A102/Bw12、O02/O02、A102/B303、A102/B101、Bw11/O02、B101/O04、Bw11/O01、Bw11/O01、A101/O02。其中有6例标本血型基因测序结果和血清学表型一致，其他4例标本的血清学表型和基因测序结果均表现出一定的差异.鉴定ABO疑难血型可利用基因分型技术结合血清学方法，最终准确鉴定血型，更好的保障输血安全.

The inhibition of aldose reductase is an effective strategy to alleviate symptoms of diabetic complications. The p-coumaric acid ethyl ester (p-CAEE) was taken as an example to investigate the inhibition of aldose reductase from p-coumaric acid derivations. The results showed p-CAEE strongly inhibited aldose reductase with the half inhibitory concentration of 1.92 μM, following the noncompetitive manner with a K

Ordinary cement is not environmentally friendly, has high cost and lacks superior performance. Many scholars use various admixtures to adjust the properties of cement slurry, but admixtures are usually not environmentally friendly, and it is difficult to ensure that the properties after deployment meet engineering requirements. In this study, a variety of admixtures were obtained using the environmental protection method, and the optimal mixing ratio was analyzed by combining the entropy weight method and the Taguchi grey relational analysis method. The developed cement slurry was compared with conventional slurry from both macroscopic and microscopic aspects. Aiming at the problem that previous scholars lacked the engineering feasibility verification of the developed slurry, this study combined the constitutive equation regression analysis method, discrete element numerical simulation and other methods to study various actual engineering conditions. The results show that the optimal mix ratio of silica fume cement slurry has good permeability characteristics under the conditions of different roughness, grouting pressure and confining pressure. At the same time, under different geological temperatures and different erosive liquid states, the cement slurry stone body shows good properties of reinforcement materials.

Objective: Macrophage-mediated inflammatory response is closely associated with the neovascularization process following hindlimb ischemia. We previously demonstrated that HO-1 (heme oxygenase-1) in macrophages evoked proinflammatory reactions and tissue damage. Here, we evaluated the role played by macrophage-derived HO-1 and elucidated its underlying molecular mechanisms in perfusion recovery after hindlimb ischemia. Approach and Results: We found significant upregulation of HO-1 in mouse ischemic muscles after hindlimb ischemia surgery and with most of this expression occurring in infiltrated macrophages. Myeloid conditional HO-1-deficient mice exhibited higher perfusion recovery, evidenced by restored blood flow, motor function and attenuated tissue damage as well as increased capillary density in the gastrocnemius muscles after hindlimb ischemia, relative to littermate controls. This protective effect was accompanied by reduced NLRP3 (Nod-like receptor family pyrin domain containing 3) inflammasome activation in the infiltrated macrophages without the alteration of macrophage infiltration and polarization. Moreover, suppressing inflammasome activation with NLRP3 inhibitor MCC950 improved blood flow and capillary density in wild-type mice compared with untreated mice. Mechanistically, suppressing HO-1 abolished TNF (tumor necrosis factor)-α-induced NLRP3 protein rather than mRNA expression in bone marrow–derived macrophages, indicating that HO-1 mediated post-transcriptional regulation of NLRP3. Furthermore, HO-1 inhibition promoted autolysosome-dependent degradation of NLRP3 in bone marrow–derived macrophages. Matrigel tube formation assay revealed that HO-1 deletion abrogated the antiangiogenic effect of inflammasome-activated macrophages. Conclusions: Taken together, these findings indicate that macrophage HO-1 deficiency promotes perfusion recovery after hindlimb ischemia by accelerating autolysosomal degradation of NLRP3. The underlying mechanism of action is a potential target for therapeutic angiogenesis in ischemic diseases.

Titanium (Ti) is a bone tissue replacement material with excellent mechanical properties. However, Ti has poor biological activity and lacks osseointegrative properties and may trigger inflammation and cause implantation failure. To address these issues, Ti surface modification has become a widely used method. In this study, using microarc oxidation (MAO) technology, a strontium-doped MAO coating was prepared on Ti surfaces in an electrolyte solution comprising calcium acetate, calcium glycerophosphate and strontium acetate. Scanning electron microscopy (SEM) and energy spectrum analysis (EDS) were used to analyze the tissue structure and elemental composition of the coating. The surface phase composition of the coating was analyzed by X-ray diffraction (XRD). We observed the proliferation of cells on the coating surface through in vitro cell experiments. The results showed the surface of the strontium-doped MAO coating is porous, and strontium is evenly distributed on the surface. The coating can promote the adhesion, proliferation and differentiation of osteoblasts and has good biological activity and thus, could potentially be applied to the surface of implants in clinical application.

White tea is a famous Chinese tea that is cooked at boiling point before drinking. The simultaneous distillation‐extraction (SDE) was used to collect volatile compounds during tea cooking. The SDE extract was dominated with green, floral, roasted and woody notes, and weak sweet note. There were 32 volatile compounds identified via gas chromatography–mass spectrometry analysis, and 19 of them had strong fragrance based on the gas chromatography‐olfactometry analyzed results. Hexanal, 2‐hexenal, cis‐3‐hexen‐1‐ol, and camphene were the main contributors to the green note. The floral note was mainly contributed by 2‐hexanone, benzeneacetaldehyde, trans‐linalool oxide, and linalool, and the sweet note was induced by trans‐β‐damascenone. The roasted note was mainly contributed by 2‐pentyl‐furan. The woody note was mainly contributed by trans‐α‐ionone and trans‐β‐ionone. Four putative reaction pathways, including amino acid degradation, carotene degradation, Maillard reaction, and glycosides hydrolysis, were figured out to explain the generation of aromatic‐active volatiles at high temperatures. This study added our knowledge on tea aroma under cooking as well as other thermal treatments., Total 32 volatile compounds were identified via gas chromatography–mass spectrometry analysis. Among them, 19 volatile substances had significant fragrance based on gas chromatography‐olfactometry analysis. Hexanal, 2‐hexenal, cis‐3‐hexen‐1‐ol, and camphene contributed green note. 2‐Hexaone, benzeneacetaldehyde, trans‐linalool oxide, and linalool contributed floral note. trans‐β‐Damascenone contributed sweet note. 2‐Pentyl‐furan contributed roasted note. trans‐α‐Ionone and trans‐β‐ionone contributed woody note. Amino acid degradation, carotene degradation, Maillard reaction, and glycosides hydrolysis were figured out to explain the generation of aromatic‐active volatiles at high temperatures.

The diverse biological activities of alginate oligosaccharides attracted extensive exploration of alginate lyases with various substrate specificity and enzymatic properties. In this study, an alginate lyase from Microbulbifer sp. ALW1, namely AlgL7, was phylogenetically classified into the polysaccharide lyase family 7 (PL7). The conserved amino acid residues Tyr606 and His499 in AlgL7 were predicted to act as the general acid/base catalysts. The enzyme was enzymatically characterized after heterologous expression and purification in E. coli. AlgL7 displayed optimal activity at 40 °C and pH 7.0. It had good stability at temperature below 35 °C and within a pH range of 5.0-10.0. AlgL7 exhibited good stability against the reducing reagent β-ME and the surfactants of Tween-20 and Triton X-100. The degradation profiles of alginate indicated AlgL7 was a bifunctional endolytic alginate lyase generating alginate oligosaccharides with the degrees of polymerization 2-4. The degradation products of sodium alginate exhibited stronger antioxidant activities than the untreated polysaccharide. In addition, AlgL7 could directly digest Laminaria japonica to produce alginate oligosaccharides. These characteristics of AlgL7 offer a great potential of its application in high-value utilization of brown algae resources.

Chondroitinase plays an important role in structural and functional studies of chondroitin sulfate (CS). In this study, a new member of chondroitinase B of PL6 family, namely ChSase B6, was cloned from marine bacterium Microbulbifer sp. ALW1 and subjected to enzymatic and structural characterization. The recombinant ChSase B6 showed optimum activity at 40 °C and pH 8.0, with enzyme kinetic parameters of Km and Vmax against chondroitin sulfate B (CSB) to be 7.85 µg/mL and 1.21 U/mg, respectively. ChSase B6 demonstrated thermostability under 60 °C for 2 h with about 50% residual activity and good pH stability under 4.0–10.0 for 1 h with above 60% residual activity. In addition, ChSase B6 displayed excellent stability against the surfactants including Tween-20, Tween-80, Trion X-100, and CTAB. The degradation products of ChSase B6-treated CSB exhibited improved antioxidant ability as a hydroxyl radical scavenger. Structural analysis and site-directed mutagenesis suggested that the conserved residues Lys248 and Arg269 were important for the activity of ChSase B6. Characterization, structure, and molecular dynamics simulation of ChSase B6 provided a guide for further tailoring for its industrial application for chondroitin sulfate bioresource development.

Aims Since little is known about the genetic diversity of lactic acid bacteria (LAB) isolates from the fermentation pit mud (FPM), we sought to evaluate the bacterial structure, identify the LAB isolates and investigate the genotype and genetic diversity of the LAB isolates. Methods and Results Using high-throughput MiSeq sequencing, we identified seven dominant bacterial genera in FPM. Lactobacillus had the highest abundance. We isolated 55 LAB strains. These isolates were all identified as Lacticaseibacillus paracasei. Using an extant multilocus sequence typing (MLST) scheme, isolates were assigned to 18 sequence types (STs) and three clonal complexes. ST1, the largest group, mainly comprised FPM isolates. Niche-specific ST2 to ST18 only contained FPM isolates. Isolates could be divided into four lineages, with most assigned to Lineage 1. Only one FPM isolate was classified as L. paracasei subsp. paracasei. Other isolates could not be classified at the subspecies level using the seven MLST loci. Conclusions Lactobacilli account for a high proportion of bacteria in pit mud. Based on the traditional culture method, L. paracasei was the dominant species, and these isolates exhibit a high ethanol tolerance, high intraspecific diversity and specific genetic profiles. Significance and Impact of the Study The study described the characterization of FPM bacterial diversity, giving an insight into the genetic diversity of L. paracasei strains present in FPM.

Soil organic carbon (SOC) is the largest carbon pool in the terrestrial ecosystem. It is not only the core index of cultivated land soil quality evaluation but also an important part of the global carbon cycle. In order to understand the response characteristics of SOC in the cultivated layer to the interaction of soil erosion and management measures, the eroded cultivated layer of typical purple soil slope farmland in the Three Gorges Reservoir area was the research object. The in-situ tests of five erosion degrees on sloping farmland were established using the shovel erosion simulation test method; taking no fertilizer (CK) as a control measure, two types of restorative management measures were set up, namely chemical fertilizer (F) and biochar+chemical fertilizer (BF), to clarify the differences in SOC content under different erosion degrees and management measures and to analyze the variation characteristics and interannual variation trend of SOC along the cultivated-layer profile. The results showed that:① BF significantly increased the soil organic carbon content in the cultivated layer of purple soil slope farmland; the SOC of BF was 90.25% and 23.84% higher than that of CK and F on average, respectively. Soil erosion significantly reduced the content of SOC (12.25%-27.74%) under CK measures, but there was no significant difference in the profile distribution of SOC under different erosion degrees. ② The SOC content in the surface layer (0-10 cm) of slope farmland was the highest, and the two measures had the most obvious effect on improving the SOC contents, which were 120.59% and 66.90%, respectively. ③ After three consecutive years of experiments, the SOC content in the cultivated-layer of slope farmland changed significantly. Under CK, the average annual loss of SOC was 12.52%, whereas under BF, the average annual increase in SOC content was 9.31%. ④ The correlation between SOC and soil physical and chemical properties was different in the various soil layers; the deeper the soil layer was, the weaker the correlation was. Therefore, biochar combined with chemical fertilizer (BF) was an important management measure to improve the erosive cultivated layer and enhance soil fertility for slope farmland in the purple hilly area. The results of this study can provide basic parameters for the rational regulation of cultivated layers and the improvement of soil fertility.